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California Health Benefits Review Program Analysis of California Senate Bill 221 HIV Associated Lipodystrophy

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Abstract and Figures

Non-partisan analysis of the medical effectiveness, cost and utilization, and public health impacts of insurance coverage for HIV Associated Lipodystrophy
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California Health
Benefits
Review Program
Analysis of California Senate Bill 221
HIV Associated Lipodystrophy
A Report to the 20172018 California State Legislature April 3, 2017
Key Findings:
Analysis of California Senate Bill 221 HIV Associated
Lipodystrophy
Summary to the 20172018 California State Legislature, April 3, 2017
Current as of April 3, 2017 www.chbrp.org i
KEY FINDINGS
BACKGROUND
Lipodystrophy associated with human immunodeficiency
virus (HIV)1 describes abnormal changes in body fat. It
may involve either or both:
Lipoatrophy abnormal fat loss in the face,
limbs, and buttocks. Facial lipoatrophy is the most
common presentation. Lipoatrophy is distinct from
HIV-related wasting, which is a general loss of fat
and lean muscle tissue.
Lipohypertrophy abnormal fat deposition in the
abdomen, breasts (in both men and women),
upper back and shoulders (“buffalo hump”), and
around the neck (“horse collar”).
Some early antiretroviral therapy (ART) drugs which
have not been recommended or commonly used in
California since 2003 are strongly correlated with HIV
associated lipodystrophy. The condition has declined
along with use of those early ART drugs. CHBRP
estimates current prevalence of HIV associated
lipodystrophy among the HIV+ enrollees to be less than
1%.
BILL SUMMARY
SB 221 would require plans and policies regulated by
either the California Department of Managed Health Care
(DMHC) or the California Department of Insurance (CDI)
to cover treatments (medical and drug) to correct, repair,
or ameliorate effects of HIV associated lipodystrophy. In
2018, approximately 24 million Californians will be
enrolled in or policies or plans regulated by CDI or DMHC
(including 7.8 million Medi-Cal beneficiaries).
1 Refer to CHBRP’s full report for full citations and references.
AT A GLANCE
The version of California Senate Bill 221 analyzed by
CHBRP would require coverage for treatments related
to HIV associated lipodystrophy. In 2018, 24 million
enrollees in plans or policies regulated by DMHC or
CDI will have health insurance that would be subject to
SB 221
1. Benefit coverage. Postmandate, 5% of these
enrollees would gain mandate-compliant
benefit coverage.
2. Utilization. Postmandate, the number of
enrollees using one or more treatments is
expected to rise from 385 to 400.
3. Expenditures. Premiums and enrollee
expenses for covered benefits (cost-sharing,
deductibles, etc.) would be increase by
$115,000 (0.0001%).
4. Medical effectiveness. A number of
treatments provide short-term relief. However,
their long-term effectiveness varies across
treatments
5. Public health. New users may experience
some short-term improvements in health and
quality of life, but it is unclear whether these
improvements will last or fade.
6. Long-term impacts. As the prevalence of HIV
associated lipodystrophy is likely to continue to
decline, the utilization, expenditure, and health
outcome impacts projected for the first year
after implementation are also expected to
decrease.
7. Medi-Calin addition to impacting the health
insurance of the 7.8 million Med-Cal
beneficiaries enrolled in a DMHC-regulated
plans (impacts included in the bullets above),
SB 221 may similarly affect the health
insurance of the additional 3.0 million
Californians associated with either the Medi-
Cal FFS program or COHS managed care.
Key Findings: Analysis of California Senate Bill 221
Current as of April 3, 2017 www.chbrp.org ii
Figure 1. Health Insurance in CA and SB 221
Source: CHBRP 2017
Notes: *Medicare beneficiaries, enrollees in self-insured products, etc.
Although the bill language is unclear, CHBRP has
assumed for this analysis that SB 221 would not prohibit
generally applicable utilization management techniques,
including application of medical necessity criteria,
requiring prior authorization, or exclusion from coverage of
treatments deemed to be experimental or investigational.
IMPACTS
Medical Effectiveness
SB 221 would require coverage for drug and
medical/surgical treatments.
CHBRP’s medical effectiveness analysis included several
medical/surgical l treatments. CHBRP found:
A preponderance of evidence that fillers increase
facial fat (i.e., reduce the visible effects of facial
lipoatrophy) and limited evidence that their effects
persist for 2 to 5 years;
Limited evidence that autologous fat
transplantation increases facial fat, but insufficient
evidence to determine how long the effect
persists; and
Insufficient evidence to determine whether fillers
improve outcomes for persons with HIV
associated buttock lipoatrophy.
Insufficient evidence to determine whether
liposuction affects outcomes for persons with
breast hypertrophy or gynecomastia.
Insufficient evidence to determine whether
lipectomy or deoxycholic acid injections improve
outcomes for persons with the form of
lipohypertrophy referred to as “buffalo hump.”
CHBRP’s medical effectiveness analysis included several
drug treatments. CHBRP found:
A preponderance of evidence that switching ART
to exclude stavudine or zidovudine, two drugs that
are no longer routinely prescribed in California,
increases facial and limb fat.
A preponderance of evidence that metformin
reduces body mass index and waist-to-hip ratio,
but may increase the likelihood of lipoatrophy;
A preponderance of evidence that tesamorelin
(Egrifta) reduces abdominal visceral fat, preserves
abdominal subcutaneous fat, and increases lean
body mass but insufficient evidence of benefits
and risks associated with long-term treatment.
A preponderance of evidence that growth
hormone reduces visceral fat. However, there is
conflicting evidence as to whether effects persist
after treatment ends. Using growth hormone is
associated with increased risk of developing
diabetes.
Benefit Coverage, Utilization, and Cost
The analysis considers SB 221’s aggregate impacts on
the medical/surgical and drug treatments most likely to be
impacted by changes in benefit coverage.
Benefit Coverage
Postmandate, the percentage of enrollees with benefit
coverage fully compliant with SB 221 would rise from 95%
to 100%.
Utilization
Postmandate, among the 24 million enrollees in DMHC-
regulated plans and CDI-regulated policies, CHBRP
estimates that an additional 15 (and so a total of 400)
Insured,
Not Subject
to Mandate*
8,952,000
Uninsured
3,079,000
Medi-Cal
COHS
1,471,000
Medi-Cal
FFS
1,519,000 CDI-Reg
658,000
DMHC-Reg
(Not Medi-
Cal)
15,554,000
DMHC-Reg
Medical
7,836,000
Health
Insurance
Regulated
by CDI or
DMHC
24,048,000
Key Findings: Analysis of California Senate Bill 221
Current as of April 3, 2017 www.chbrp.org iii
enrollees would use of treatments for HIV associated
lipodystrophy.
Expenditures
Postmandate, as a result of the changed benefit coverage
among the 24 million enrollees in DMHC-regulated plans
and CDI-regulated policies, premium expenditures would
increase by $115,000 (0.0001%).
As would be expected, some enrollees using newly
compliant benefit coverage would incur some cost
sharing, Although enrollees with newly compliant benefit
coverage may have paid for some treatments during the
baseline period, CHBRP cannot estimate the frequency
with which such situations may have occurred and so
cannot estimate the total expense for such situations.
Postmandate, such expenses would be gone, though
enrollees with newly compliant benefit coverage might,
postmandate, pay for some treatments for which coverage
is denied (e.g., through utilization management review).
Some enrollees who always had compliant benefit
coverage might also pay for some treatments. Again,
CHBRP cannot estimate the frequency of such situations.
Medi-Cal
To the extent permitted by federal law, SB 221 would
require the same benefit coverage for all Medi-Cal
beneficiaries, including those with health insurance
through County Organized Health System (COHS)
managed care and those associated with the fee-for-
service (FFS) program. Therefore, in addition to the Medi-
Cal beneficiaries enrolled in DMHC-regulated plans, SB
221 could affect benefit coverage for another 3 million
Med-Cal beneficiaries who are either enrolled in County
Organized Health System (COHS) managed care or
engaged in Medi-Cal’s fee-for-service (FFS) system. In
addition to the expected increase of $104,000 in
premiums CHBRP is estimating for the 7.8 million Medi-
Cal beneficiaries enrolled in DMHC-regulated plans (a
figure which represents a 0.0004% increase in premiums),
it seems reasonable to assume that a population
proportional increase of $19,455 would occur for the 1.5
million beneficiaries enrolled in COHS managed care. It
seems likely that a similar impact would occur for the 1.5
million beneficiaries with health insurance through the FFS
program (though the exact amount is unknown).
CalPERS
CHBRP estimates no measurable change in premium
impacts for CalPERS.
Number of Uninsured in California
CHBRP would expect no measurable impact of SB 221 on
the number of uninsured persons.
Public Health
In the first year, postmandate, CHBRP would expect some
increase in use of treatments by about 15 enrollees in
DMHC-regulated plans and CDI-regulated policies. For
those persons, there may be some improvements in
health and quality of life.
Long-Term Impacts
Because the prevalence of HIV associated lipodystrophy
appears to have declined along with use of early
antiretroviral drugs there may be a shrinking number of
persons for whom the treatments are medically necessary.
This suggests that the utilization and expenditure impacts
projected in this analysis for the first year after
implementation of SB 221 would decline over time.
Furthermore, although treatments may, to varying
degrees, provide short-term relief from the burden of
symptoms, there is little or no evidence of long-term
effectiveness. The lack of long-term effectiveness may
both decrease utilization over time and may suggest that
initial improvements in health outcomes may fade.
Essential Health Benefits and the
Affordable Care Act
Because medically necessary treatments for HIV
associated lipodystrophy are generally covered by health
insurance in California, including the state’s benchmark
plan, it seems that SB 221 would not exceed the definition
of essential health benefits (EHBs) in California. However,
the possibility that the language of the bill would
prohibit generally applicable utilization management
techniques, including application of medical necessity
criteria, or exclusion from coverage of treatments
deemed to be experimental or investigational makes it
unclear whether the bill would exceed EHBs.
A Report to the California State Legislature
Analysis of California SB 221
HIV Associated Lipodystrophy
April 3, 2017
California Health Benefits Review Program
1111 Broadway, Suite 1400
Oakland, CA 94607
Tel: 510.287.3876
Fax: 510.763.4253
www.chbrp.org
Analysis of California Senate Bill 221
Current as of April 3, 2017 www.chbrp.org v
The California Health Benefits Review Program (CHBRP) was established in 2002. As per its authorizing
statute, CHBRP provides the California Legislature with independent analysis of the medical, financial,
and public health impacts of proposed health insurance benefit bills. The state funds CHBRP through an
annual assessment on health plans and insurers in California.
An analytic staff in the University of California’s Office of the President supports a task force of faculty and
research staff from several campuses of the University of California to complete each CHBRP analysis. A
strict conflict-of-interest policy ensures that the analyses are undertaken without bias. A certified,
independent actuary helps to estimate the financial impact, and content experts with comprehensive
subject-matter expertise are consulted to provide essential background and input on the analytic
approach for each report.
More detailed information on CHBRP’s analysis methodology, authorizing statute, as well as all CHBRP
reports and other publications are available at www.chbrp.org.
Analysis of California Senate Bill 221
Current as of April 3, 2017 www.chbrp.org vi
TABLE OF CONTENTS
Key Findings .................................................................................................................... i
List of Tables and Figures ............................................................................................. viii
Policy Context ................................................................................................................. 1
Bill-Specific Analysis of SB 221 Lipodystrophy ............................................................ 1
Analytic Approach and Key Assumptions ..................................................................... 1
Interaction With Existing Requirements ........................................................................ 2
Background on HIV Associated Lipodystrophy ............................................................... 5
Risk Factors ................................................................................................................. 5
Effects of Untreated Lipodystrophy .............................................................................. 6
Prevalence of HIV and Lipodystrophy in California ...................................................... 7
Medical Effectiveness .................................................................................................... 10
Research Approach and Methods .............................................................................. 10
Methodological Considerations .................................................................................. 11
Outcomes Assessed .................................................................................................. 11
Study Findings ........................................................................................................... 12
Summary of Findings ................................................................................................. 19
Benefit Coverage, Utilization, and Cost Impacts ........................................................... 24
Analytic Approach ...................................................................................................... 24
Baseline and Postmandate Benefit Coverage ............................................................ 25
Baseline and Postmandate Utilization ........................................................................ 26
Baseline and Postmandate Per-Unit Cost .................................................................. 26
Baseline and Postmandate Expenditures ................................................................... 26
Other Considerations for Policymakers ...................................................................... 28
Public Health Impacts .................................................................................................... 33
Analytic Approach ...................................................................................................... 33
Estimated Public Health Outcomes ............................................................................ 33
Long-Term Impacts ....................................................................................................... 35
Long-Term Utilization and Cost Impacts .................................................................... 35
Long-Term Public Health Impacts .............................................................................. 35
Appendix A Text of Bill Analyzed .............................................................................. A-1
Appendix B Literature Review Methods .................................................................... B-1
Appendix C Cost Impact Analysis: Data Sources, Caveats, and Assumptions ........ C-1
Analysis of California Senate Bill 221
Current as of April 3, 2017 www.chbrp.org vii
Appendix D Information Submitted by Outside Parties ............................................ D-4
References
California Health Benefits Review Program Committees and Staff
Acknowledgments
Analysis of California Senate Bill 221
Current as of April 3, 2017 www.chbrp.org viii
LIST OF TABLES AND FIGURES
Table 1. SB 221 Impacts on Benefit Coverage, Utilization, and Cost Among Persons With Health
Insurance Regulated by DMHC or CDI, 2018 ........................................................................................... ix
Table 2. Treatments for HIV Associated Lipodystrophy Syndrome ........................................................... 10
Table 3. Treatment-Specific Baseline Period Estimates ............................................................................ 25
Table 4. Baseline Per Member Per Month Premiums and Total Expenditures by Market Segment,
California, 2018 ........................................................................................................................................ 29
Table 5. Postmandate Per Member Per Month Premiums and Total Expenditures by Market Segment,
California, 2018 ........................................................................................................................................ 31
Figure 1. Health Insurance in CA and SB 221 .............................................................................................. ii
Figure 2. Antiretroviral Drugs ..................................................................................................................... 19
Figure 3. Fillers for Facial Lipoatrophy ....................................................................................................... 20
Figure 4. Autologous Fat Transplantation .................................................................................................. 20
Figure 5. Fillers for Buttock Lipoatrophy .................................................................................................... 21
Figure 6. Lipectomy .................................................................................................................................... 21
Figure 7. Deoxycholic Acid Injections ........................................................................................................ 21
Figure 8. Metformin .................................................................................................................................... 22
Figure 9. Tesamorelin ................................................................................................................................ 22
Figure 10. Growth Hormone ....................................................................................................................... 23
Analysis of California Senate Bill 221
Current as of April 3, 2017 www.chbrp.org ix
Table 1. SB 221 Impacts on Benefit Coverage, Utilization, and Cost Among Persons With Health
Insurance Regulated by DMHC or CDI, 2018
Baseline
Postmandate
Decrease
Percentage
Change
Benefit coverage
Total enrollees in DMHC/CDI-regulated
plans/policies (a)
24,048,000
24,048,000
0%
Percentage of enrollees in DMHC/CDI-
regulated plans/policies with health
insurance subject to SB 221
100%
100%
0%
Percentage of enrollees in DMHC/CDI
plans/policies with fully SB 221 compliant
health insurance
95%
100%
5%
Utilization and unit cost
Utilization of HIV associated lipodystrophy treatments per 1,000 enrollees
Medical/surgical (e)
0.0284
0.0298
5.0%
Drug (f)
0.0158
0.0162
2.7%
Average annual unit cost/user of HIV associated lipodystrophy treatments
Medical/surgical (e)
$789
$829
5.0%
Drug (f)
$1,096
$1,125
2.7%
Expenditures
Premium expenditures by payer
Private employers for
group insurance (j)
$64,820,615,000
$64,820,615,000
0.0000%
CalPERS HMO
employer expenditures
for DMHC-regulated
plans (c)(j)
$4,884,262,000
$4,884,262,000
0.0000%
Medi-Cal Managed
Care Plan expenditures
for DMHC-regulated
plans (h)
$27,983,856,000
$27,983,960,000
0.0004%
Enrollees for
individually purchased
insurance
$14,608,214,000
$14,608,223,000
0.0001%
Individually
purchased outside
exchange (j)
$6,304,061,000
$6,304,061,000
0.0000%
Individually
purchased
Covered California
$8,304,153,000
$8,304,162,000
0.0001%
Enrollees with group
insurance, CalPERS
HMOs, Covered
California, and Medi-
Cal Managed Care (b)
$20,387,090,000
$20,387,091,000
0.0000%
Enrollee expenses
For covered benefits (deductibles,
copayments, etc.)
$13,565,623,000
$13,565,624,000
$1,000
0.0000%
For noncovered benefits (d)(i)
Total expenditures
$146,249,665,000
$146,249,775,000
$115,000
0.0001%
Source: California Health Benefits Review Program, 2017.
Notes: (a) This population includes persons with privately funded (including Covered California) and publicly funded
(e.g., CalPERS HMOs, Medi-Cal Managed Care Plans) health insurance products regulated by DMHC or CDI.
Analysis of California Senate Bill 221
Current as of April 3, 2017 www.chbrp.org x
Population includes enrollees aged 0 to 64 years and enrollees 65 years or older covered by employer-sponsored
health insurance.
(b) Premium expenditures by enrollees include employee contributions to employer-sponsored health insurance and
enrollee contributions for publicly purchased insurance.
(c) Of the increase in CalPERS employer expenditures, about 56.7% would be state expenditures for CalPERS
members who are state employees or their dependents. It should be noted, however, that should CalPERS choose to
make similar adjustments for consistency to the benefit coverage of enrollees associated with CalPERS’ self-insured
products, the fiscal impact on CalPERS could be greater.
(d) Due to relevant income restrictions, CHBRP assumes no measurable expense for Medi-Cal beneficiaries enrolled
in DMHC-regulated plans.
(e) Includes only those expenses that are paid directly by enrollees to providers for services related to the mandated
benefit that are not currently covered by insurance. In addition this only includes those expenses that will be newly
covered, post-mandate. Other components of expenditures in this table include all health care services covered by
insurance.
(f) Medical treatments considered include liposuction / lipectomy, gynecomastia surgery, injections / fillers, and
autologous fat transplantation.
(g) Drug treatments considered include tesamorelin.
(h) In addition to the possible increase of $104,000 increase in premiums CHBRP is estimating for the 7.8 million
Medi-Cal beneficiaries enrolled in DMHC-regulated plans, CHBRP assumes that a proportional increase of $19,455
would occur for the 1.5 million beneficiaries enrolled in COHS managed care. It seems likely that there would also be
an additional increase for the 1.5 million beneficiaries with health insurance through the FFS program (though the
exact amount is unknown).
(i) Although enrollees with newly compliant benefit coverage may have paid for some treatments before SB 221,
CHBRP cannot estimate the frequency with which such situations may have occurred or and so cannot estimate the
total expense such situations might have incurred. Postmandate, such expenses would be gone, though enrollees
with newly compliant benefit coverage might, postmandate, pay for some treatments for which coverage is denied
(through utilization management review), as some enrollees who always had compliant benefit coverage may have
done and may continue to do, postmandate. Again, CHBRP cannot estimate the frequency with which such situations
might occur, and or the total expense such situations might incur.
(j) No measurable impact is projected.
Key: COHS = County Organized Health Systems; CalPERS HMOs = California Public Employees’ Retirement
System Health Maintenance Organizations; CDI = California Department of Insurance; DMHC = Department of
Managed Health Care; FFS = fee-for-service.
Analysis of California Senate Bill 221
Current as of April 3, 2017 www.chbrp.org 1
POLICY CONTEXT
The California Senate Committee on Health has requested that the California Health Benefits Review
Program (CHBRP)2 conduct an evidence-based assessment of the medical, financial, and public health
impacts of SB 221 (Wiener) Lipodystrophy.
If enacted, SB 221 could affect the health insurance of approximately 24.1 million Californians who will
have health insurance regulated by the California Department of Managed Health Care (DMHC) or the
California Department of Insurance (CDI) in 2018. This figure includes 7.8 million Medi-Cal beneficiaries
enrolled in DMHC-regulated plans. In addition, SB 221 would be relevant to the benefit coverage of 1.5
million beneficiaries enrolled in County Organized Health System (COHS) managed care and another 1.5
million beneficiaries engaged in Medi-Cal’s fee-for-service (FFS) program. The full 27.1 million represent
69% of Californians.
Bill-Specific Analysis of SB 221 Lipodystrophy
SB 221 would, when a provider has indicated the treatment is necessary due to HIV associated
lipodystrophy, require DMHC-regulated plans and CDI-regulated policies to cover treatments (medical
and drug) to correct, repair, or ameliorate effects of HIV associated lipodystrophy. Lipodystrophy includes
both abnormal fat accumulation (lipohypertrophy) and/or abnormal fat loss (lipoatrophy).”Treatments
would be inclusive of (but not limited to):
Reconstructive surgery, such as suction-assisted lipectomy;
Dermal injections or fillers for reversal of facial lipoatrophy; and
Other restorative procedures.
To the extent permitted by federal law, SB 221 would require the same benefit coverage for all Medi-Cal
beneficiaries.
The full text of SB 221 can be found in Appendix A .
Explanations of the relevant treatments are included in in the Medical Effectiveness section of this report
and additional information about the condition, HIV associated lipodystrophy, is present in the
Background section.
Analytic Approach and Key Assumptions
The bill indicates that coverage shall be subject to a statement from a treating provider indicating medical
necessity. For this analysis, CHBRP has assumed that the bill would not prohibit generally applicable
utilization management techniques, including application of medical necessity criteria, requiring prior
authorization, or exclusion from coverage of treatments deemed to be experimental or investigational.
However, the language of the bill is unclear as to whether such utilization management
techniques would be allowed.
2 CHBRP’s authorizing statute is available at http://chbrp.org/faqs.php.
Analysis of California Senate Bill 221
Current as of April 3, 2017 www.chbrp.org 2
The bill includes alterations to the Welfare & Institutions (W&I) Code that, if permitted by federal law,
would ensure that all Medi-Cal beneficiaries have similar coverage for treatment of HIV associated
lipodystrophy. For this analysis, CHBRP has assumed that alteration of the W&I Code would impact
benefit coverage of Medi-Cal Beneficiaries enrolled in County Organized Health System (COHS)
managed care and Medi-Cal beneficiaries whose general health insurance is through the fee-for-service
(FFS) program. However, prior to a federal decision (which is not available at this time), the effect
the bill would have through alteration of the W&I Code is unknown.
General Caveat for All CHBRP Analyses
It is important to note that CHBRP’s analysis of proposed legislation address the incremental effects
how the proposed legislation would impact benefit coverage, utilization, costs, and public health.
CHBRP’s estimates of these incremental effects are presented in this report.
Interaction With Existing Requirements
Health benefit mandates may interact with state and/or federal mandates. SB 221 would appear to
overlap with one of each and is similar to a benefit mandate present in one other state.
State Requirements
California law and regulations
CHBRP is aware of a California benefit mandate that requires all DMHC-regulated plans and CDI-
regulated policies to cover reconstructive surgery to correct or repair abnormal structures of the body
caused by congenital defects, developmental abnormalities, trauma, infection, tumors, or disease to
improve function or to create a normal appearance, to the extent possible.3 This law appears relevant to
treatment of HIV associated lipodystrophy. Although reasonably referred to as “medical,” since they are
covered by health insurance under a “medical benefit,” lipectomy, autologous fat transplantation, and
gynecomastia surgery could, in the presence of HIV associated lipodystrophy, be considered medically
necessary reconstructive surgery.
Similar requirements in other states
For treatment of HIV associated lipodystrophy, CHBRP is aware of one state with a similar benefit
mandate (BCBSA, 2016). In 2016, Massachusetts passed into law S.2137,4 which requires coverage for
treatment of HIV associated lipodystrophy. The Massachusetts law language is very similar to the
language in SB 221.
3 Health & Safety Code 1367.63 and Insurance Code 10123.88.
4 The MA language is available at https://malegislature.gov/Bills/189/S2137.
Analysis of California Senate Bill 221
Current as of April 3, 2017 www.chbrp.org 3
Federal Requirements
Medicare
For treatment of HIV associated lipodystrophy, CHBRP is aware that Medicare covers facial
injections/fillers when depression is a comorbidity,5 covers lipectomy in California,6 and covers
gynecomastia in other states.7
Affordable Care Act
A number of Affordable Care Act (ACA) provisions described below have the potential to or do interact
with state benefit mandates. Below is an analysis of how SB 221 may interact with requirements of the
ACA as presently exists in federal law, including the requirement for certain health insurance to cover
essential health benefits (EHBs).8
Any changes at the federal level may impact the analysis or implementation of this bill, were it to pass into
law. However, CHBRP analyzes bills in the current environment, given current law.
Essential health benefits
State health insurance marketplaces, such as Covered California, are responsible for certifying and
selling qualified health plans (QHPs) in the small-group and individual markets. QHPs are required to
meet a minimum standard of benefits as defined by the ACA as EHBs. In California, EHBs are related to
the benefit coverage available in the Kaiser Foundation Health Plan Small Group Health Maintenance
Organization (HMO) 30 plan, the state’s benchmark plan for EHBs.9,10
States may require QHPs to offer benefits that exceed EHBs.11 However, a state that chooses to do so
must make payments to defray the cost of those additionally mandated benefits, either by paying the
purchaser directly or by paying the QHP.12,13 State rules related to provider types, cost-sharing, or
5 See 2010 bulletin / change request.
6 See Local Coverage Determination L35163. Considered reconstructive surgery when performed to alleviate specific
conditions.
7 See Local Coverage Determination L35090, Considered a second line treatment (drug discontinuance should first
be considered).
8 The ACA requires nongrandfathered small-group and individual market health insurance including but not limited
to QHPs sold in Covered California to cover 10 specified categories of EHBs. Resources on EHBs and other ACA
impacts are available on the CHBRP website: http://www.chbrp.org/other_publications/index.php.
9 The U.S. Department of Health and Human Services (HHS) has allowed each state to define its own EHBs for 2014
and 2015 by selecting one of a set of specified benchmark plan options. CCIIO, Essential Health Benefits Bulletin.
Available at: cciio.cms.gov/resources/files/Files2/12162011/essential_health_benefits_bulletin.pdf.
10 H&SC Section 1367.005; IC Section 10112.27.
11 ACA Section 1311(d)(3).
12 State benefit mandates enacted on or before December 31, 2011, may be included in a state’s EHBs, according to
the U.S. Department of Health and Human Services (HHS). Patient Protection and Affordable Care Act: Standards
Related to Essential Health Benefits, Actuarial Value, and Accreditation. Final Rule. Federal Register, Vol. 78, No. 37.
February 25, 2013. Available at: www.gpo.gov\fdsys\pkg\FR-2013-02-25\pdf\2013-04084.pdf.
13 However, as laid out in the Final Rule on EHBs HHS released in February 2013, state benefit mandates enacted
on or before December 31, 2011, would be included in the state’s EHBs, and there would be no requirement that the
state defray the costs of those state-mandated benefits. For state benefit mandates enacted after December 31,
2011, that are identified as exceeding EHBs, the state would be required to defray the cost.
Analysis of California Senate Bill 221
Current as of April 3, 2017 www.chbrp.org 4
reimbursement methods would not meet the definition of state benefit mandates that could exceed
EHBs.14
Because medically necessary treatments for HIV associated lipodystrophy are generally covered by
health insurance in California, including the state’s benchmark plan, it seems that SB 221 would not
exceed the definition of EHBs in California. However, the possibility that the language of the bill
would prohibit generally applicable utilization management techniques, including application of
medical necessity criteria, or exclusion from coverage of treatments deemed to be experimental
or investigational makes it unclear whether the bill would exceed EHBs.
14 Essential Health Benefits. Final Rule. A state’s health insurance marketplace would be responsible for determining
when a state benefit mandate exceeds EHBs, and QHP issuers would be responsible for calculating the cost that
must be defrayed.
Analysis of California Senate Bill 221
Current as of April 3, 2017 www.chbrp.org 5
BACKGROUND ON HIV ASSOCIATED LIPODYSTROPHY
Lipodystrophy, clinically recognized as a specific set of symptoms in body fat distribution and appearance
observed among HIV-infected patients, was first recognized in 1998, and has had a decline in prevalence
since shortly after its recognition, following the introduction of antiretroviral therapies with less
lipodystrophy-related side effects in the early 2000’s (Carr et al., 1998; Carter et al., 2001; Nguyen et al.,
2006). Lipodystrophy may occur in men, women, and children, and typically progresses unless
therapeutically managed (Baril et al., 2005). For the purposes of this review, the term lipodystrophy will be
applied broadly to describe abnormal changes in body fat distribution and metabolism related to HIV and
HIV treatment.
Lipodystrophy presents as two clinically distinct conditions, or a mixture of both:
Lipoatrophy: fat loss in the face, limbs, and buttocks, of which facial lipoatrophy is the most
common presentation (Bacchetti et al., 2005; Guaraldi et al., 2013). Lipoatrophy is distinct from
HIV-related wasting, which is a general loss of fat and lean muscle tissue (Lichtenstein, 2005).
Lipohypertrophy: fat deposition in the abdomen, breasts (in both men and women), upper back
and shoulders (“buffalo hump”), and around the neck (“horse collar”) (Guaraldi et al., 2013).
Lipohypertrophy is sometimes referred to as lipodeposition or lipoaccumulation. This fat can be
subcutaneous (“pinchable”) or visceral, which wraps around internal organs.
Lipodystrophy is a chronic condition, and there is currently no cure for the underlying metabolic
dysfunction that causes lipodystrophy; rather, treatments for lipodystrophy comprise a set of preventive
strategies and medical or surgical interventions to ameliorate lipodystrophy-associated body changes. For
a detailed discussion of treatments for lipodystrophy, see the Medical Effectiveness section.
Risk Factors
The literature suggests that risk for lipodystrophy is multifactorial. Numerous epidemiologic studies have
documented risks associated with intrinsic biological traits and processes such as gender and aging
(Bacchetti et al., 2005; FRAM, 2006; Guaraldi et al., 2014; Jacobson et al., 2005), and with the severity
and duration of HIV infection (Guaraldi et al., 2013; Jacobson et al., 2005; Lichtenstein, 2005; McDermott
et al., 2005). However, lipodystrophy has been most strongly correlated with use of antiretroviral
therapies (medications that prevent HIV from progressing to AIDS). In particular, certain combinations of
nucleoside reverse transcriptase inhibitors and protease inhibitors drug classes used in antiretroviral
therapy (ART) regimens have been linked to both clinical presentations of lipodystrophy (most strongly
with lipoatrophy and less so with lipohypertrophy) (Jacobson et al., 2005; McDermott et al., 2005; Miller et
al., 2003; Moyle et al., 2010), and may interact synergistically when used in combination therapy
(Guaraldi et al., 2013; Shlay et al., 2009). Since 2003, however, the primary drugs implicated in
presentation of lipodystrophy have not been prescribed in contemporary antiretroviral regimens, and
subsequently, the number of new cases of lipodystrophy have decreased (Nguyen et al., 2008).
Although many patients present with a mixed syndrome, the causes of lipodystrophy differ by subgroup
presentation:
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Lipoatrophy
The primary risk factor for lipoatrophy (fat loss) is exposure to certain antiretroviral medications, in
particular the drugs stavudine or zidovudine, which are thought to interrupt mitochondrial function
(Guaraldi et al., 2013; Lichtenstein, 2005), and are not currently recommended for use in HIV. In a 2005
review of large epidemiologic studies, stavudine use was significantly associated with lipoatrophy in six of
nine studies (Lichtenstein, 2005). Risk of lipoatrophy with zidovudine is less established, but has been
documented in longitudinal cohorts and clinical trial settings (McDermott et al., 2005; Shlay et al., 2009).
Lipoatrophy is also closely linked to higher HIV viral load, lower body fat at baseline, and duration of
antiretroviral medication use (Jacobson et al., 2005; Lichtenstein, 2005; McDermott et al., 2005; Shlay et
al., 2009).
Lipohypertrophy
Compared with lipoatrophy, lipohypertrophy is not as strongly associated with antiretroviral therapies.
Although fat accumulation with protease inhibitor use has been documented, lipohypertrophy has not
been linked to specific medications and can occur, to varying degrees, with any treatment regimen
(Guaraldi et al., 2013; Lichtenstein, 2005; Shlay et al., 2009). Rather, epidemiologic studies suggest that
lipohypertrophy risk may be more directly mediated by biological and lifestyle factors. Among an HIV-
positive cohort of subjects participating in the U.S.-based National Health and Nutrition Examination
Survey, risk for lipohypertrophy was higher among women, subjects with a greater proportion of body fat
at baseline, and high triglyceride levels (Jacobson et al., 2005). Among a large Italian cohort, incidence of
lipohypertrophy increased progressively with each year of observation, suggesting that lipohypertrophy
risk is associated with the aging process itself (Guaraldi et al., 2014).
Effects of Untreated Lipodystrophy
Although lipodystrophy is not considered to be a life-threatening condition, lipoatrophy and
lipohypertrophy are both associated with metabolic abnormalities that may increase a patient’s risk for
cardiovascular disease (Lake et al., 2011). Furthermore, the physical presentation of lipodystrophy is
associated with quality-of-life deficits and social isolation (Collins et al., 2000; Guaraldi et al., 2008;
Leclercq et al., 2013; Power et al., 2003). Patients experiencing fat accumulation in the breasts, back,
and chin areas have reported restricted range of movement, back pain, and breathing difficulties
(Cofrancesco et al., 2009), whereas patients with lipoatrophy reported discomfort when sitting or lying
down (Power et al., 2003). Furthermore, appearance changes resulting from lipodystrophy, particularly
facial lipoatrophy, are linked to depression, decreased self-esteem, sexual dysfunction, and social
isolation; which may be due in part to concern that the effects of lipodystrophy are a recognizable
indicator of HIV status (Collins et al., 2000; Guaraldi et al., 2007; Leclercq et al., 2013). Although
awareness may be low among the general public, lipodystrophy has been recognized as “the new
Kaposi’s sarcoma” which led to highly recognizable facial lesions among communities
disproportionately affected by HIV (Power et al., 2003).
Prior to the discontinuation of the primary medications known to cause lipoatrophy, fear of lipodystrophy-
associated morbidities may have caused patients to switch to less effective regimens or discontinue use
overall (Power et al., 2003). The literature linking lipodystrophy with HIV treatment adherence is mixed
(Guaraldi et al., 2008); however, a French study evaluating antiretroviral use among HIV-infected patient
found that up to 30% of participants discontinued treatment after experiencing one lipodystrophy-
associated symptom.
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Prevalence of HIV and Lipodystrophy in California
According to the California Department of Public Health Office of HIV/AIDS, an estimated 126,000 people
were living with an HIV/AIDS diagnosis in California as of December 2014 (Office of AIDS, 2016a).
Between 2010 and 2014, the yearly number and rate of new HIV/AIDS diagnoses decreased; however,
the number of people living with an HIV/AIDS diagnosis in California increased over that same period of
time (Office of AIDS, 2016b). This trend is attributed to prolonged life expectancy among individuals living
with HIV due to antiretroviral therapies and improved access to medical care (Eckert, 2012).
Although there are many people living with HIV in California, for the following reasons, the prevalence of
lipodystrophy in the population subject to the changes proposed in SB 221 is uncertain:
Due to the lack of an objective case definition for lipodystrophy, estimates of lipodystrophy
prevalence among the HIV-infected population vary widely, ranging from 11% to 83%, and
estimates may not be comparable across time and setting (Carr et al., 2003; Carter et al., 2001;
Guaraldi et al., 2013). For example, among a single cohort of HIV-positive Australian men, Carter
et al. (2001) showed that lipodystrophy prevalence estimates ranged from 19% to 65%,
depending on which definition and measurements were utilized.
The majority of available prevalence estimates were generated from cohorts exposed to the
principle antiretroviral medications associated with lipodystrophy. In the early 2000’s, stavudine
and zidovudine were replaced on lists of recommended HIV treatments with newer medications,
leading to a decrease in incidence of lipodystrophy, particularly lipoatrophy, among patients using
antiretroviral medications (Nguyen et al., 2008). However, the most recent studies assessing the
prevalence of lipodystrophy among U.S. patients were conducted in cohorts recruited in the late
1990s (Bacchetti et al., 2005; FRAM, 2006; Jacobson et al., 2005; Lichtenstein et al., 2001;
Palella et al., 2004). Contemporary cohort studies, (i.e., conducted in populations recruited post-
2003) were subject to selection bias (Guaraldi et al., 2014) or were conducted in resource-limited
countries where stavudine and zidovudine are still prescribed due to their low price relative to
other drugs (Mercier et al., 2009; Signorini et al., 2010; van Griensven et al., 2007).
It is difficult to disaggregate the symptoms of obesity-related metabolic dysfunction (i.e., diabetes)
and lifestyle and age-related accumulation of body fat from HIV associated lipohypertrophy. HIV-
positive patients experiencing prolonged life expectancy through use of antiretroviral medications
are now thought to be susceptible to chronic conditions and weight gain attributed to aging and
poor diet, rather than the HIV infection itself (Guaraldi and Baraboutis, 2009).
CHBRP’s estimates of current prevalence in California, less than 1% of the HIV+ population, are
much lower than literature estimates. This could reflect a continued reduction in lipodystrophy
prevalence, limited billing for lipodystrophy medical care, or both.
Following removal of the early ARTs from recommended treatment, new diagnoses of HIV associated
lipodystrophy have become much less common (Nguyen et al., 2008). This decrease, along with deaths
of some of the HIV+ persons who were diagnosed with HIV associated lipodystrophy, has resulted in a
much reduced number of Californians living with the condition.15
15 Personal communication, E. Murphy, March 8, 2017.
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Health Disparities16 in Lipodystrophy
“’Health disparity’ denotes differences, whether unjust or not. ‘Health inequity’ on the other hand, denotes
differences in health [status or] outcomes that are systematic, avoidable, and unjust.” (Wyatt et al., 2016).
Despite the lack of a reasonable prevalence estimate and the presumably decreasing incidence of
lipodystrophy, there are known differences in the incidence of HIV associated lipodystrophy syndrome by
age, gender, race/ethnicity. Consistent with the majority of literature on lipodystrophy, these differences
are typically described by clinical presentation group: lipoatrophy, lipohypertrophy, or mixed syndrome.
CHBRP found no literature identifying inequities in the overall burden of lipodystrophy.
Race/Ethnicity
Differences in prevalence of lipodystrophy exist by racial/ethnic group. Although it is unclear to what
extent the broad presentation of lipodystrophy differs by race or ethnicity, several studies have found
white race to be significantly associated with lipoatrophy (Lichtenstein, 2005). White participants in the
multisite, US-based HIV Outpatient Study (HOPS) were almost five times more likely to develop
lipoatrophy during a year of observation compared with nonwhites (Lichtenstein et al., 2003); moreover
whites enrolled in the Ontario Cohort Study (OCS) a cohort of HIV-infected Canadian adults taking ART
reported more severe lipoatrophy symptoms than their nonwhite comparators (Andany et al., 2011). In
contrast, no studies have described statistically significant racial/ethnic differences in the prevalence of
lipohypertrophy. However almost 40% of black participants in the OCS reported fat accumulation
compared with 30% of whites and 26% of other races (Andany et al., 2011).
CHBRP found no literature addressing lipodystrophy-related disparities in quality of life by race or
ethnicity.
Gender
Gender differences in lipodystrophy prevalence have been well-documented. There is some
disagreement as to whether gender differences exist in the overall presentation of lipodystrophy (Andany
et al., 2011; Galli et al., 2003; Miller et al., 2003); however, men are significantly more likely to experience
lipoatrophy than women, who are more likely to develop lipohypertrophy. Men and women are equally
likely to present with a mixed syndrome (Andany et al., 2011; Bacchetti et al., 2005; FRAM, 2006; Galli et
al., 2003; Jacobson et al., 2005; Leclercq et al., 2013; Miller et al., 2003; Verolet et al., 2015). Compared
with women, men in the previously discussed Ontario Cohort Survey (OCS) were almost twice as likely to
experience some form of lipoatrophy and present with more severe symptoms (Andany et al., 2011).
Additionally, the literature suggests that facial lipoatrophy (the most common form of lipoatrophy) may be
more prevalent in men (Andany et al., 2011; Miller et al., 2003), with one French study reporting that HIV-
treated men were 2.6 times more likely than women to have facial lipoatrophy (Leclercq et al., 2013). By
contrast, women in the Ontario Cohort Study were 2.3 times more likely than their male counterparts to
experience lipohypertrophy, particularly in the abdomen and breasts, and reported more severe
symptoms associated with fat accumulation (Andany et al., 2011).
16 Several competing definitions of “health disparities” exist. CHBRP relies on the following definition:
Health disparity is defined as the difference in health outcomes between groups within a population. While the terms
may seem interchangeable, health disparityis different from health inequity.’ ‘Health disparitydenotes differences,
whether unjust or not. Health inequity,on the other hand, denotes differences in health [status or] outcomes that are
systematic, avoidable, and unjust.” Wyatt et al., 2016.
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A more limited body of literature suggests that the impact of lipodystrophy on quality of life is unevenly
distributed between men and women. Women in both French and Swiss cross-sectional cohort studies
reported overall lower quality of life associated with lipodystrophy compared with men; moreover, Swiss
women were more likely to present with anxiety and depression (Leclercq et al., 2013; Verolet et al.,
2015).
Age
CHBRP identified few studies addressing differences in lipodystrophy prevalence and risk by age. One
cross-sectional study of an HIV-positive cohort in Australia documented a three-fold increase in risk for
lipodystrophy at age 50 years and older compared with patients aged younger than 35 years (Miller et al.,
2003). Additionally, persons aged 50 years and older in the previously discussed HOPS study were
almost three times as likely to have lipoatrophy, and two times as likely to experience lipohypertrophy
compared with participants aged 30 to 39 years (Lichtenstein et al., 2001). However, given that
lipodystrophy is strongly associated with exposure to early antiretroviral regimens, these observed age
trends may be proxies for exposure to what are now out-of-date regimens and overall duration of
treatment.
Age was not independently associated with differential lipodystrophy-related quality-of-life impacts,
although anecdotal evidence from qualitative studies suggests that younger people may experience a
greater psychological impact due to the body shape changes and appearance of early aging caused by
lipodystrophy (Power et al., 2003).
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MEDICAL EFFECTIVENESS
As discussed in the Introduction, SB 221 would mandate coverage of treatments for HIV associated
lipodystrophy syndrome, which encompasses lipoatrophy and lipohypertrophy. The medical effectiveness
review summarizes findings from the literature from 2002 to present on the effectiveness of treatments for
HIV associated lipoatrophy and lipohypertrophy.
The medical effectiveness review discusses evidence of the effectiveness of the treatments listed in SB
221, which include, but are not limited to, “reconstructive surgery, such as suction assisted lipectomy,
other restorative procedures and dermal injections or fillers for reversal of facial lipoatrophy syndrome,” as
well as other treatments for HIV associated lipoatrophy and lipohypertrophy that are discussed in
guidelines issued by the Health Resources and Services Administration (HRSA, 2014) or were identified
by CHBRP’s content expert.17
Table 2. Treatments for HIV Associated Lipodystrophy Syndrome
Lipoatrophy
Lipohypertrophy
Preventive strategies
Switching to an antiretroviral therapy
(ART) drug regimen that avoids ARTs
associated with lipoatrophy
Diet
Exercise
Medical/surgical interventions
Injectable synthetic fillers for facial or
buttock lipoatrophy (temporary or
permanent)
Autologous fat transplantation
Surgical fat removal (e.g., lipectomy
or liposuction of buffalo hump or
breast reduction mammoplasty)
Deoxycholic acid injections (Kybella)
Prescription drugs
Metformin
Tesamorelin (Egrifta)
Growth hormone
Source: CHBRP, 2017 (adapted from HRSA, 2014)
Research Approach and Methods
Studies of treatments for HIV associated lipodystrophy were identified through searches of PubMed, the
Cochrane Library, Web of Science, EconLit, Business Source Complete, the Cumulative Index of Nursing
and Allied Health Literature (CINAHL), and PsycINFO. Websites maintained by the following
organizations that produce and/or index meta-analyses and systematic reviews were also searched: the
Agency for Healthcare Research and Quality (AHRQ), the International Network of Agencies for Health
Technology Assessment (INAHTA), the National Health Service (NHS) Centre for Reviews and
17 Personal communication, E. Murphy, March 2017.
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Dissemination, the National Institute for Health and Clinical Excellence (NICE), and the Scottish
Intercollegiate Guideline Network.
The search was limited to abstracts of studies published in English. The search was limited to studies
published from 2002 to present. CHBRP relied on a systematic review published in 2011 for findings from
studies on growth hormone and a synthetic analog of growth hormone (tesamorelin) published prior to
2011. CHBRP relied on a systematic review published in 2015 for findings from studies on fillers and
autologous fat transplantation published prior to 2015. CHBRP relied on two systematic reviews
published in 2013 for findings from studies on antiretroviral therapy (ART) drugs published prior to 2013.
CHBRP relied on a systematic review published in 2010 for findings from studies on insulin sensitizing
drugs published prior to 2010. Of the 338 articles found in the literature review, 50 were reviewed for
potential inclusion in this report on SB 221, and a total of 20 studies were included in the medical
effectiveness review for this report. The other articles were eliminated because they did not focus on HIV
associated lipodystrophy, were of poor quality, or did not report findings from clinical research studies. A
more thorough description of the methods used to conduct the medical effectiveness review and the
process used to grade the evidence for each outcome measure is presented in Appendix B: Literature
Review Methods.
Methodological Considerations
The term HIV associated lipodystrophy typically refers to changes in fat distribution that are often
associated with increased risk for cardiovascular disease and metabolic abnormalities, including
dyslipidemia (elevated cholesterol and/or fat in the blood) and insulin resistance (diabetes and pre-
diabetes). Insulin resistance refers to a person’s resistance to the hormone insulin, resulting in increasing
blood sugar. This can eventually lead to type 2 diabetes. Lipodystrophy includes both lipoatrophy (fat
loss) and lipohypertrophy (fat gain) which appear to be separate processes that should be addressed
independently in a given patient, if they coexist. Patients with lipoatrophy have loss of subcutaneous
(pinchable) fat (most noticeably in the limbs, face, and/or buttocks areas). Patients with lipohypertrophy
have a gain of visceral fat in the abdomen and may have dorsocervical fat pad enlargement (buffalo
hump) and breast enlargement. In contrast to subcutaneous fat, visceral fat in the abdomen is usually not
treated by surgical or ultrasonic procedure because it is wrapped around important internal organs, such
as the liver, intestines, and pancreas. Procedures to extract fat wrapped around these organs are not
recommended due to the risk of injury to these organs. This report discusses treatments and outcomes
for lipoatrophy and lipohypertrophy separately.
Outcomes Assessed
Studies of HIV associated lipodystrophy have examined the effects of treatments on the following
objective measures of outcomes: cheek thickness, mean cheek volume, facial fat thickness, reduction in
visceral fat, reduction in subcutaneous fat, lean body mass, and body mass index.
Subjective outcome measures include: patient's self-perception of improvement, body image perception,
depression as assessed by a visual analogue scale score (VAS), the Facial Lipoatrophy Grading Scale,
the Assessment of Body Change and Distress questionnaire (ABCD), and the Beck Depression Inventory
(BDI) questionnaire.
The HRSA guidelines for diagnosis and treatment of HIV associated lipodystrophy indicate that some
persons with HIV may consider discontinuing or interrupting ART due to lipodystrophy (HRSA, 2014).
However, CHBRP did not identify any studies on the impact of treating HIV associated lipodystrophy on
adherence to ART.
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Study Findings
As discussed in the Background section the ART drugs associated with lipodystrophy have not been
recommended or routinely prescribed in the United States since 2003.
Preventive Strategies
Lipoatrophy
There are more than 25 ART drugs in six classes that are usually used in combination to treat HIV
infection.18 ART drugs are broadly classified by the phase of the retrovirus lifecycle that the drug inhibits.
These six classes include the nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), non-
nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), a fusion inhibitor (FI), a
CCR5 antagonist, and integrase strand transfer inhibitors (INSTIs). Typical combinations include two
NRTIs as a "backbone" along with one NNRTI, PI, or INSTI as a "base."
Multiple open-label randomized controlled trials (RCTs)19 have assessed the impact of differences in ART
treatment regimens on lipoatrophy.
A systematic review of open-label RCTs found that exposure to NRTIs that are thymidine analogues (in
particular stavudine and zidovudine) is a major factor associated with peripheral lipoatrophy (defined as
>20% loss of limb fat). Patients on NRTI-sparing regimens showed a significantly lower incidence of
peripheral lipoatrophy than patients on NRTI-containing regimens (de Waal et al., 2013).
Modifying the antiretroviral regimen so that stavudine or zidovudine is replaced with a different NRTI,
specifically tenofovir or abacavir (ABC), is another medical approach to lipoatrophy that increases facial
and limb fat. A systematic review of open-label RCTs by de Waal et al. (2013), found that participants
who were switched away from thymidine analogue-containing NRTI regimens gained limb fat over time
compared with participants who continued NRTI or thymidine analogue-containing regimens, who
generally lost limb fat. Another systematic review of RCTs (Cruciani et al., 2013) also reported that two of
three RCTs included in the systematic review that assessed ABC-containing regimens found that persons
on ABC-containing regimens had lower incidence of lipoatrophy.
Studies have not found evidence that switching a PI to a different third drug reduces lipoatrophy (de Waal
et al., 2013; Fisac et al., 2005).
Lipohypertrophy
Eating a healthier diet and exercising regularly are standard recommendations for preventing fat
accumulation and achieving weight loss. The HRSA guidelines recommend that clinicians encourage all
persons with HIV to engage in moderate aerobic exercise, and state that studies have found that exercise
can reduce visceral fat without producing lipoatrophy (HRSA, 2014). The guidelines indicate that no
studies have been conducted on the impact of a healthier diet on lipohypertrophy, but it stands to reason
that eating more healthfully would improve the overall health of persons with lipohypertrophy.
18 ARTs are sometimes referred to as antiretroviral therapy (ARV), combination antiretroviral therapy (cARV), or
highly active antiretroviral therapy (HAART).
19 Open-label RCTs are RCTs in which researchers and participants know which treatment participants are receiving.
This is a weaker study design than a blinded RCT because knowledge of the treatment a participant receives may
influence perception of the effectiveness of the treatment.
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Switching from a NRTI-containing or thymidine analogue-containing ART regimen does not reduce trunk
and/or visceral fat. de Waal and colleagues’ systematic review of open-label RCTs (2013) found that
there were no significant changes in trunk and/or visceral fat over time for those who were switched away
from NRTI-containing regimes compared to those who continued NRTI-containing regimes or thymidine
analogue-containing regimens (de Waal et al., 2013).
CHBRP did not identify any studies that address the impact of diet and exercise on lipohypertrophy.
However, it stands to reason that eating more healthfully would improve the overall health of persons with
lipohypertrophy.
There is a preponderance of evidence that switching to an antiretroviral regimen that does not include
stavudine or zidovudine increases facial and limb fat based on two systematic reviews of RCTs, but there
is insufficient evidence regarding the impact of modifying ART regimen on lipohypertrophy, specifically
trunk and/or visceral fat based on one systematic review.
Medical and Surgical Treatments
Lipoatrophy
Facial fillers
Facial contouring is used to restore the faces of persons with lipoatrophy to a more typical appearance.
Approaches to facial contouring that have been studied include autologous fat transfer, as well as
minimally invasive procedures, such as the use of the injectable filler devices. Fillers include poly-L-lactic
acid (PLLA), calcium hydroxylapatite (CaHA), hyaluronic acid (HA), polyacrylamide gel (PAAG),
polyalkylimide gel (PAIG), polymethylmethacrylate (PMMA), and silicone oil. Studies suggest there are
benefits, including high patient satisfaction and significantly improved quality of life, as evidenced by
improvement in scores for quality of life on visual analog scales and increased tissue depth measured by
computed tomography imaging, with few serious adverse events (Jagdeo et al., 2015).
Studies that examine both facial fillers and fat transplantation
A large systematic review of 76 studies that compared multiple fillers and autologous fat transplantation
found that the studies demonstrated sustained improvement in facial lipoatrophy severity for 12 to 18
months with PLLA, CaHA, HA, and silicone oil injections, and up to 4 to 5 years with autologous fat
transplantation, PAAG, PAIG, and PMMA injections. The degree and duration of improvement for each
treatment option is closely related to the severity of lipoatrophy prior to treatment and the biophysical and
longevity profile of each filler agent. Some patients experienced adverse events, such as pain, discomfort,
ecchymosis (skin discoloration), edema (swelling), and erythema (reddening of skin due to injury or
irritation) that usually resolved within 1 month (Jagdeo et al., 2015).
Most of the studies included in the Jagdeo et al. systematic review were observational studies without
comparison groups. None of the studies compared persons treated with fillers to a comparison group that
was not treated, and PLLA and PAIG are the only fillers for which persons treated immediately were
compared with persons whose treatment was delayed. It is also important to note that interstudy
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comparison among studies was difficult because different scales were used to measure objective and
subjective outcomes. Additionally, the authors of the Jagdeo systematic review point out the lack of RCTs
with direct head-to-head comparisons to evaluate the efficacy and safety of different fillers (Jagdeo et al.,
2015).
One of the few studies to make a head-to-head comparison is an observational study that compared
persons who received autologous fat transplantation with persons who received a filler (PLLA or PAAG)
(Guaraldi et al., 2005). At 24 weeks post-treatment, the two groups had similar increases in dermal and
subcutaneous thickness, and satisfaction with appearance improved in both groups.
Studies included in the systematic review suggest that the effects of some fillers persist for at least 2
years. Four case reports demonstrated PLLA treatment reduced severity of lipoatrophy for up to 2 years,
and eight studies reported that persons treated with PAAG had improvement in cheek thickness at 2 to 5
years after treatment. One study of PMMA found that patients reported better quality of life 2 years after
treatment (Jagdeo et al., 2015). However, the research designs of these studies are weak because they
do not include comparison groups.
Studies of autologous fat transplantation
One uncontrolled observational study examined 15 subjects with facial lipoatrophy who were treated with
fat transplantation using Coleman's technique of harvesting abdominal fat and injecting it into the face.
The treatment resulted in increases in facial fat thickness lasting for up to 24 weeks, with a majority of
patients (13 of 15) being happy with the result (Levan et al., 2002).
One uncontrolled observational study, comparing 26 patients pre- and postoperatively, treated with fat
transplantation using Coleman's technique to evaluate the long-term viability of fat grafting found a
statistically significant improvement in mean cheek volume (P < 0.001) that was maintained for 12 months
following treatment (Fontdevila et al., 2008).
Based on evidence from a large systematic review that included both RCTs and observational studies
without comparison groups, there is a preponderance of evidence that fillers decrease the visible effects
of HIV associated facial lipoatrophy and are associated with high patient satisfaction. There is limited
evidence from one systematic review that the effects of fillers persist for 2 to 5 years following treatment.
There is limited evidence from one observational study with a comparison group and two uncontrolled
observational studies that autologous fat transplantation increases facial fat for up to 12 months post
treatment.
Studies of fillers for buttock lipoatrophy
Lipoatrophy of the buttocks may cause both functional (e.g., pain when sitting) and esthetic problems.
One 18-month prospective, open-label, pre-post of 10 HIV-infected subjects with buttock lipoatrophy who
were unable to sit for more than 30 minutes because of pain (Claude et al., 2015) found mean pain score
reduction, an increase in mean time that subjects could remain seated, and increased mental health
scores after treatment with hyaluronic acid gel fillers. At 6 months after treatment, 9 subjects (90%)
experienced decreased pain after 15 minutes of sitting. The mean time that subjects could remain seated
was 37 minutes longer compared with baseline for up to 12 months for all subjects for whom data were
recorded (n = 5). The mean mental health score on the Medical Outcomes Study-HIV questionnaire
increased significantly from baseline to 9 months. Scores were not significantly different from baseline at
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other time points. Patients experienced only mild adverse events, such as redness or swelling at the
injection site. This study had limited long-term data because of subjects being lost to follow-up.
One observational study of 156 patients who received PMMA fillers for lipoatrophy of the buttocks found
that most of the patients (93%) were satisfied with the treatment and reported more comfort when seated
and that they had been able to be seated for longer periods of time (Serra et al., 2015).
There is insufficient evidence that fillers decrease the effects of HIV associated lipoatrophy in the buttocks
based on two pre-post studies without comparison groups, although stands to reason that use of fillers
could make sitting more comfortable because the fillers replace fat tissue in the buttocks.
Lipohypertrophy
Liposuction and lipectomy
Liposuction includes both suction-assisted lipectomy (SAL) and ultrasonic-assisted liposuction (UAL), and
are options for various manifestations of lipohypertrophy, including breast lipohypertrophy in women or
gynecomastia in men, and fat deposition in the neck and jaw. Liposuction is not used to treat
lipohypertrophy in the abdomen because that is due to an increase in visceral fat within the peritoneal
cavity rather than subcutaneous fat. Liposuction can be used to remove visceral fat in the peritoneal
cavity but is not recommended due to the risk of damage to internal organs.20
CHBRP did not identify any studies of the use of liposuction to treat breast hypertrophy in women or
gynecomastia in men.
Cervicodorsal lipodystrophy, or "buffalo hump" deformity, is a common form of lipohypertrophy. Evidence
from several small uncontrolled studies suggests that the use of excisional lipectomy to correct
cervicodorsal lipodystrophy can decrease neck strain and improve range of motion and satisfaction with
appearance (Connolly et al., 2004; Gold and Annino, 2005; Hultman et al., 2007; Ion and Raveendran,
2011; Roostaeian et al., 2008; Warren and Borud, 2008). One study reported that 3 of 10 patients had
partial recurrence between 12 to 30 months following lipectomy (Hultman et al., 2007). An important
weakness of these studies is that they did not include comparison groups.
CHBRP did not identify any studies of the use of liposuction to treat breast lipohypertrophy in women or
gynecomastia in men. However, it stands to reason that liposuction would remove excess fat from the
breast area and, thus reduce breast size.
Based on six uncontrolled studies with small sample sizes, there is insufficient evidence that lipectomy
decreases the visible effects of HIV associated lipohypertrophy. However, it stands to reason that
lipectomy removes excess fat in patients with HIV associated “buffalo hump” deformity, which is likely to
alleviate symptoms, such as difficulty sleeping, neck pain, limited range of motion in upper extremities,
and disfigurement, and, thus, improve quality of life. However, it is important to note that the duration of
impact these treatments have is unknown because only one study tracked patients for more than 1 year.
20 Personal communication, E. Murphy, March 2017.
Analysis of California Senate Bill 221
Current as of April 3, 2017 www.chbrp.org 16
Studies of deoxycholic acid injections (Kybella)
The Food and Drug Administration has recently approved deoxycholoic acid injections (Kybella) as a
treatment for severe convexity or fullness associated with submental fat (i.e., double chin). Some
physicians are also using it to treat HIV associated lipohypertrophy.21 CHBRP found no studies that
assessed the effects of deoxycholic acid injections on HIV associated lipohypertrophy.
CHBRP found no studies of the impact of deoxycholic acid injections on HIV associated lipohypertrophy.
Prescription Drugs
Lipoatrophy
No prescription drugs are recommended for treatment of lipoatrophy aside from the preventive strategy of
switching to an ART regimen that avoids drugs that place patients at higher risk for experiencing
lipoatrophy. CHBRP also found no studies that assessed the effects of other prescription drugs on
lipoatrophy.
CHBRP found no studies of the impact of prescription drugs on lipoatrophy, aside from the preventive
strategy of switching to an ART regimen that avoids drugs that place patients a high risk for lipoatrophy, a
strategy that has been followed in the United States since 2003.
Lipohypertrophy
Insulin-sensitizing agents (metformin) on lipohypertrophy
One meta-analysis of RCTs of multiple insulin-sensitizing drugs found that metformin, compared with
rosiglitazone or pioglitazone, was the only insulin sensitizer to demonstrate beneficial effects on HIV
associated lipohypertrophy. Six unique trials compared metformin to placebo or no treatment in 287
subjects with one or more symptoms of lipohypertrophy, regardless of insulin status, over a mean
duration of 27 months. Use of metformin was associated with statistically significant reductions in body
mass index and waist-to-hip ratio. Three trials directly compared metformin to rosiglitazone and effects on
measures of fat redistribution all favored metformin (Sheth and Larson, 2010).
According to the HRSA guidelines, metformin has been modestly effective in treating visceral fat in
patients with insulin resistance, but may exacerbate lipoatrophy. Additionally, metformin should be used
with caution in patients with chronic liver or renal disease (HRSA, 2014).
21 Personal communication, E. Murphy, March 2017.
Analysis of California Senate Bill 221
Current as of April 3, 2017 www.chbrp.org 17
Based on evidence from a systematic review of nine RCTs, there is a preponderance of evidence that
metformin reduces body mass index and waist-to-hip ratio relative to a placebo and to rosiglitazone.
Tesamorelin
Studies have assessed the effects of several forms of growth hormone on HIV associated
lipohypertrophy. Evidence suggests that tesamorelin, an injectable synthetic analogue of human growth
hormone-releasing factor (GHRH), significantly reduces visceral fat, preserves abdominal subcutaneous
fat, increases lean body mass, and improves body mass index. Findings about reduction in visceral fat
are especially important because visceral fat is more strongly related to diabetes and other poor health
outcomes than other types of fat.
A systematic review of double-blinded placebo-controlled RCTs examined the effects of growth hormone
treatments on visceral fat, subcutaneous fat, and lean body mass (Sivakumar et al., 2011). Four RCTs
included in the systematic review evaluated tesamorelin. The duration of treatment was either 12 or 26
weeks. The authors pooled findings from the four RCTs of tesamorelin and found that tesamorelin
reduced visceral fat and increased lean body mass, but did not change subcutaneous fat.
One study published after the studies included in the systematic review pooled data from two RCTs of
tesamorelin (Mangili et al., 2015). The study of 806 persons found that subjects treated with tesamorelin
had 3.9 times the odds of a reduction in visceral fat to <140 cm2 after 6 months of treatment with
tesamorelin than subjects randomized to receive a placebo in analyses that adjusted for gender, body
mass index, and amount of visceral fat prior to treatment.22
None of the six RCTS reported whether the effects of treatment with tesamorelin persist after treatment
ends. The HRSA guidelines state that patients quickly regain visceral fat after tesamorelin is discontinued
(HRSA 2014). If tesamorelin treatment must continue indefinitely to maintain reduction in visceral fat,
some persons with HIV associated lipohypertrophy may not choose to pursue it or may discontinue
treatment because they find it burdensome.
Based on evidence from a systematic review of RCTs and an RCT published after the studies included in
the systematic review, there is a preponderance of evidence that tesamorelin reduces abdominal visceral
fat, preserves abdominal subcutaneous fat, and increases lean body mass. There is insufficient evidence
about risks, or benefits, such as improved quality of life, with long-term treatment or whether benefits
persist after treatment is discontinued.
Growth Hormone
Studies have assessed the effects of several forms of growth hormone on HIV associated
lipohypertrophy, including recombinant growth hormone (rhGH) and growth hormone releasing hormone
22 In this study, persons with baseline MetS-NCEP (metabolic syndrome), elevated triglyceride levels, or white race
were most likely to experience reductions in visceral fat after 6 months of tesamorelin treatment.
Analysis of California Senate Bill 221
Current as of April 3, 2017 www.chbrp.org 18
(GHRH). Evidence suggests that recombinant growth hormone (rhGH) significantly reduce visceral fat,
preserves abdominal subcutaneous fat, increases lean body mass, and improves body mass index.
A large systematic review of double-blinded placebo-controlled RCTs identified six RCTs that compared
growth hormone treatments to a placebo and assessed effects on visceral fat, subcutaneous fat, and lean
body mass (Sivakumar et al., 2011). Pooled findings from the six RCTs indicate that rhGH reduces
visceral fat and subcutaneous fat and may also increase lean body mass. Patients who received rhGH
had higher rates of arthralgias (joint pain) and peripheral edema (swelling in peripheral vascular tissue,
usually in the lower limbs) than patients who received the placebo.
One open-label RCT not included in the systematic review (Bickel et al., 2006) compared visceral fat at
baseline to visceral fat following 12 weeks and 24 weeks for 26 persons who were randomly assigned to
one of two rhGH treatment regimens. One group was given 4 mg of rhGH per day for 12 weeks followed
by 2 mg per day for 12 more weeks, and the other group was given 4 mg of rhGH three times per week
for 12 weeks followed by 2 mg per day for 12 weeks. The two rhGH treatment regimens resulted in similar
reductions in visceral fat relative to baseline. The ratio of visceral fat to total fat also decreased in both
groups. There were no differences in facial fat or limb fat, suggesting that treatment did not increase the
risk of lipohypertrophy in those parts of the body. Adverse effects were more common among persons in
the group that received the larger dose of rhGH during the first 12 weeks and included dyspepsia
(stomach pain), peripheral edema, transient hyperglycemia (high blood sugar), and pain in the
extremities. A follow-up nonrandomized observational study of 16 persons enrolled in the RCT found that
overall visceral fat remained 18% below baseline at a median of 9 months following the end of treatment
(Bickel et al., 2008).
One important adverse effect of growth hormone is that it increases the risk of developing diabetes. An
open-label RCT (Macallan et al., 2008) compared persons who received rhGH alone with persons who
received rhGH plus rosiglitazone, a drug used to treat diabetes. Receiving rosiglitazone in addition to
rhGH prevented patients from experiencing an increase in fasting insulin but did not change the effect on
visceral fat. However, as Macallan notes, rosiglitazone is associated with adverse cardiac events.
An important limitation of most of the studies of growth hormone treatments is limited follow-up after
patients are treated. Aside from Bickel (2008) and Macallan et al. (2008), they provide little information
about whether the effects of growth hormone treatment persist after patients stop receiving treatment.
Macallan et al.’s (2008) findings suggest that patients regain visceral fat after treatment with rhGH ends,
whereas Bickel et al (2008) found that reduction in visceral fat persisted a median of 9 months following
treatment. The authors of the systematic review also noted that they did not identify any studies that
examined the risks and benefits of use of growth hormone for an extended period of time (Sivakumar et
al., 2011).
The systematic review of double-blinded placebo-controlled RCTs also examined the effects of growth
hormone releasing hormone (GHRH) on visceral fat, subcutaneous fat, and lean body mass (Sivakumar
et al., 2011). The one RCT in the systematic review that evaluated GHRH found increases in lean body
mass, but no difference in visceral or subcutaneous fat (Koutkia et al., 2004).
Based on evidence from a systematic review of RCTs, there is a preponderance of evidence from RCTs
that rhGH reduces visceral fat. There is conflicting evidence about whether the effects of growth hormone
treatments persist after patients stop taking them. One important adverse effect of growth hormone is that
it increases the risk of developing diabetes. There is insufficient evidence regarding other risks and
benefits associated with long-term treatment.
Analysis of California Senate Bill 221
Current as of April 3, 2017 www.chbrp.org 19
Summary of Findings
The charts in this section summarize CHBRP’s findings regarding the strength of the evidence for the
effects of specific medications, treatments, and services relevant to SB 221. Separate charts are
presented for each medication, treatment, or service for which the bill would mandate coverage and for
each outcome for which evidence of the effectiveness of a treatment is available. The title of the chart
indicates the medication, treatment or service for which evidence is summarized. The statement under
the heading “Conclusion” presents CHBRP’s conclusion regarding the strength of evidence about the
effect of a particular medication, treatment, or service on a specific relevant outcome and the number of
studies on which CHBRP’s conclusion is based. For medications, treatments, and services for which
CHBRP concludes that there is clear and convincing, preponderance, limited, or conflicting evidence, the
placement of the vertical bar indicates the strength of the evidence. If CHBRP concludes that evidence is
insufficient, a graph that states “Insufficient Evidence” will be presented.
Figure 2. Antiretroviral Drugs
Conclusion
CHBRP finds preponderance of evidence that switching to an antiretroviral regimen that does not include
stavudine or zidovudine is effective in increasing facial and limb fat based on two systematic reviews of
RCTs.
Analysis of California Senate Bill 221
Current as of April 3, 2017 www.chbrp.org 20
Figure 3. Fillers for Facial Lipoatrophy
Conclusion
Preponderance of evidence that fillers increase facial fat (i.e., reduce the visible effects of facial
lipoatrophy) based on a systematic review of 76 studies with multiple types of research designs. There is
insufficient evidence to determine how long the effects of fillers persist following treatment.
Figure 4. Autologous Fat Transplantation
Conclusion
Limited evidence that autologous fat transplantation increases facial fat (i.e., reduces the visible effects of
facial lipoatrophy) based on two studies. There is insufficient evidence to determine how long the effects
of autologous fat transplantation persist following treatment.
Analysis of California Senate Bill 221
Current as of April 3, 2017 www.chbrp.org 21
Figure 5. Fillers for Buttock Lipoatrophy
Conclusion
Insufficient evidence to determine whether fillers for buttock lipoatrophy improve outcomes for persons
with HIV associated buttock lipoatrophy and how long the effects last based on two studies.
Figure 6. Lipectomy
Conclusion
Insufficient evidence to determine whether lipectomy improves outcomes for persons with “buffalo hump”
deformity based on six uncontrolled studies.
Figure 7. Deoxycholic Acid Injections
Conclusion
Insufficient evidence to determine whether deoxycholic acid injections improve outcomes for persons with
HIV associated lipohypertrophy because there are no studies.
Analysis of California Senate Bill 221
Current as of April 3, 2017 www.chbrp.org 22
Figure 8. Metformin
Conclusion
Clear and convincing evidence that metformin reduces body mass index and waist-to-hip ratio among
persons with HIV associated lipohypertrophy based on one meta-analysis of six RCTs.
Figure 9. Tesamorelin
Conclusion onclusion
Based on evidence from a systematic review of RCTs and an RCT published after the studies included in
the systematic review, there is a preponderance of evidence that tesamorelin reduces abdominal visceral
fat, preserves abdominal subcutaneous fat, and increases lean body mass. There is insufficient evidence
about risks, or benefits, such as improved quality of life, with long-term treatment, or whether the benefits
of tesamorelin persist after treatment is discontinued.
Analysis of California Senate Bill 221
Current as of April 3, 2017 www.chbrp.org 23
Figure 10. Growth Hormone
Conclusion
Preponderance of evidence based on one meta-analysis of RCTs and four additional RCTs that growth
hormone reduces visceral fat but treatment is associated with increased risk of diabetes. There is also
conflicting evidence about whether reduction in visceral fat persists after treatment ends.
Analysis of California Senate Bill 221
Current as of April 3, 2017 www.chbrp.org 24
BENEFIT COVERAGE, UTILIZATION, AND COST IMPACTS
This section reports on benefit coverage, utilization, and overall cost related to the potential incremental
impacts of SB 221. SB 221 would require DMHC-regulated plans and CDI-regulated policies to cover
medical or drug treatments to correct or repair disturbances of body composition caused by human
immunodeficiency virus (HIV) associated lipodystrophy syndrome, including, but not limited to,
Reconstructive surgery, such as suction assisted lipectomy;
Other restorative procedures; and
Dermal injections or fillers for reversal of facial lipoatrophy syndrome.
To the extent permitted by federal law, SB 221 would require the same benefit coverage for all Medi-Cal
beneficiaries. Therefore, in addition to impacting the benefit coverage of the 7.8 million Medical
beneficiaries enrolled in DMHC-regulated plans, SB 221 could also apply to the benefit coverage of the
1.5 million Medi-Cal beneficiaries enrolled in County Organized Health System (COHS) managed care
and the additional 1.5 million beneficiaries engaged in Medi-Cal’s fee-for-service (FFS) program.
Analytic Approach
Although SB 221 is an exception (because it would alter the Welfare & Institutions Code as well), the
benefit coverage of the 3 million Medi-Cal beneficiaries associated with COHS and FFS are not
commonly subject to the proposed legislation CHBRP considers (because neither is subject to the
California Health & Safety Code or the California Insurance Code, which regulate DMHC-regulated plans
and CDI-regulated policies). The analysis which follows, unless otherwise specified, is relevant to the 24
million Californians enrolled in a plan or policy regulated by DMHC or CDI (a figure which does includes
7.8 million Medi-Cal beneficiaries enrolled in DMHC-regulated plans).
At baseline, (without implementation of SB 221), the percentage of enrollees with health insurance fully
compliant with SB 221 is 95%. For those with fully compliant health insurance, we assume that their
health insurance postmandate will not change (and service use will remain the same postmandate). For
the 5% at baseline with health insurance not fully compliant with SB 221, we assume postmandate
insurance will be compliant with SB 221 (and the service use will match the pattern of the other 95%).
The benefit coverage, cost, and utilization impact analysis does include some of the treatments discussed
in the Medical Effectiveness section. Preventive treatment (switching to newer ARTs) is not included
because CHBRP believes coverage for such changes to have been present for all HIV+ enrollees and
that all California enrollees switched soon after the 2003 recommendations supports doing so (see
Background section). CHBRP also assumes no postmandate change in the use of metformin, as
metformin is a relatively inexpensive and relatively common drug that is also used in treatment of
diabetes. Assuming most people with HIV associated lipodystrophy had premandate benefit coverage for
metformin, metformin has not been included in the impact analysis. In term of growth hormone, CHBRP
identified no measurable evidence of use among persons with compliant coverage at baseline, and so
assumes there will be no measurable postmandate use in the year following implementation of SB 221,
so growth hormone has not been included in the impact analysis. Like the drug treatments already
discussed, a new medical/surgical treatment, deoxycholic acid injections (Kybella) has not been included
in the impact analysis. Although there is anecdotal discussion of off-label use as a treatment for a
particular form of lipohypertrophy (buffalo hump), CHBRP cannot estimate what would presumably be
limited (by prevalence of the specific subcondition) potential utilization and has not included deoxycholic
acid injections in the impact analysis. In summary, not included in the impact analysis are metformin,
Analysis of California Senate Bill 221
Current as of April 3, 2017 www.chbrp.org 25
growth hormone or deoxycholic acid injections. Respective average annual unit costs for these
treatments are $6, $750 and $340.
CHBRP includes the following treatments for HIV associated lipodystrophy in the benefit coverage, cost
and utilization analysis: 1) lipectomy; 2) gynecomastia surgery; 3) injection/fillers; 4) autologous fat
transplantation; and 5) tesamorelin (Egrifta). The first four are considered “medical/surgical” treatments,
covered under an enrollee’s medical benefit, and tesamorelin is considered a “drug” treatment, covered
under an enrollee’s OPD benefit. Additionally, a simple two-category treatment categorization allows the
consideration of three types of potential benefits to patients from this mandate: 1) gaining coverage for
medical/surgicaltreatments; 2) gaining coverage for tesamorelin (drug) treatment; or 3) gaining both
types of coverage. The aggregation into two main treatment categories “medical/surgical” and “drug”
allows the analysis to address some complexity without becoming too unwieldy.
As noted in the Policy Context section, CHBRP has assumed that SB 221 would require benefit
coverage, but would not affect utilization management (prior authorization requirements and medical
review for medical treatments, and use of formularies). Further discussion of bill-specific caveats and
assumptions are detailed in Appendix C where further details on the underlying data sources and
methods also appear.
Baseline and Postmandate Benefit Coverage
As noted in Table 1, currently, 95% of enrollees with health insurance regulated by DMHC or CDI have
benefit coverage that is fully compliant with SB 221. Postmandate analyses consider when this is
increased to 100%.
Current coverage of the HIV associated lipodystrophy treatments was determined by a survey of the
largest (by enrollment) providers of health insurance in California. Responses to this survey represent
85% of enrollees with private market health insurance that can be subject to state mandates. Queries
were also sent to CalPERS, to California Department of Health Care Services (related to Medi-Cal
benefits), and to several of the larger (by enrollment) Medi-Cal Managed Care Plans to understand
impacts on other affected market segments. Results were used to estimate the percentage of enrollees
who had HIV associated lipodystrophy treatment coverage at baseline.
Where Table 1 presents baseline and postmandate aggregates, Table 3, below, presents the baseline
specifics for treatments included in the benefit coverage, cost, and utilization impact analysis.
Table 3. Treatment-Specific Baseline Estimates
Treatment Category
Enrollees With SB 221
Compliant Benefit
Coverage
Annual
Units Used
Average
Annual Unit
Cost Per User
Medical/surgical treatments
Lipectomy 95% 51 $3,027
Gynecomastia surgery 95% 35 $14,208
Injection/fillers 95% 502 $409
Autologous fat transplantation 95% 95 $1,515
Drug treatments
Tesamorelin (Egrifta) 97% 380 $3,314
Source: CHBRP, 2017.
Analysis of California Senate Bill 221
Current as of April 3, 2017 www.chbrp.org 26
Baseline and Postmandate Utilization
To prepare the reader for the findings in this section, it is important to remember the SB 221 mandate
affects enrollees with benefit coverage that is already almost entirely fully compliant (e.g., SB 221
increases compliance from 95% to 100%). In addition, the quantity of potential users of treatments
affected by the mandate will be quite small. CHBRP estimates less than 1% of the HIV+ population has
lipodystrophy. Given the considerably higher figures estimated in the early literature, it seems that there
has been a drastic reduction in the prevalence HIV associated lipodystrophy. The context for SB 221 is
that of mandate that would affect health insurance that is almost already fully compliant and that the
number of potential users with changed benefit coverage (CHBRP estimates that the number as
approximately 15) is limited. For these reasons, Estimates of the utilization and expenditure (premium
and enrollee cost sharing) impacts are smaller than one might initially expect in a state the size of
California. Specifically, among the 24 million enrollees in DMHC-regulated plans and CDI-regulated
policies, postmandate, CHBRP estimates a total of 400 enrollees would use of treatments for HIV
associated lipodystrophy (an additional 15 more than at baseline), and as a result of this changed benefit
coverage, premium expenditures would increase by $114,000 (0.0001%).
As noted in Table 1, baseline use of “medical/surgical” treatments per 1,000 enrollees among enrollees in
DMHC-regulated plans and CDI-regulated policies is estimated to be 0.0284. For the drug treatment
tesamorelin, the baseline estimated use is 0.0158 per 1,000 enrollees. These rates are expected to
increase to 0.0298 and 0.0162, postmandate. This corresponds to increases of 0.0014 and 0.0004,
respectively or in percentage terms, 5.0% and 2.7%.
The magnitude of the change can also be appreciated through the number of users at baseline and
postmandate. At baseline, there are 385 users of treatment. Table 3 presents the distribution of the
treatments being used. This can be found in the column labeled Annual Units Used. Postmandate,
CHBRP estimates that there will be 400 users. This is a gain of 15 more users (about 4%) related to
increasing from 95% to 100% the percentage of enrollees with health insurance fully compliant with SB
221.
Baseline and Postmandate Per-Unit Cost
Given the limited changes in benefit coverage and utilization, CHBRP anticipates no impact on unit costs.
Aggregate unit costs are presented in Table 1, and treatment-specific unit costs are presented in Table 3.
Baseline and Postmandate Expenditures
Table 4 and Table 5 present baseline and postmandate expenditures by market segment for enrollees in
DMHC-regulated plans and CDI-regulated policies. The tables present per member per month (PMPM)
premiums, enrollee expenses for both covered and noncovered benefits, and total expenditures
(premiums as well as enrollee expenses).
Table 5 indicates that SB 221 would increase total net annual expenditures by $110,000 or 0.0001% for
enrollees with DMHC-regulated plans and CDI-regulated policies, postmandate. This is mainly due to the
administrative costs associated with providing coverage for the benefit to persons who do not currently
have it.
Analysis of California Senate Bill 221
Current as of April 3, 2017 www.chbrp.org 27
Premiums
Table 5 shows a $114,000 (0.0001%) increase in total premiums (composed of an average portion of
premium paid by employers of $104,000 and an average portion of premium paid by employee of
$10,000). As noted in Table 1, the distribution of the impact on premiums varies. CHBRP estimates
nearly no change in total premiums for private employers purchasing group health insurance and
CalPERS HMOs. CHBRP estimates no measurable change in total premiums for purchasers of group
insurance and an increase of $9,000 (0.0001%) in premiums in the individual market. CHBRP estimates
that state expenditures for Medi-Cal Managed Care Plans would increase by $104,000 (0.0004%).
The overall percent change in insured premiums is 0.0001% (Table 5), but changes in premiums appear
to vary by market segment. For the Small Group Markets (both CDI and DMHC-regulated) CHBRP
estimates no change in premiums. There is some variability in the impacts on Publicly Funded plans with
DMHC-regulated Medi-Cal Managed Care Plans expecting a 0.0004% increase in insured premiums for
those <65 years, but a 0.0001% increase in insured premiums for those 65 years.
In addition to the expected $104,000 increase in premiums, CHBRP is estimating for the 7.8 million Medi-
Cal beneficiaries enrolled in DMHC-regulated plans, it seems reasonable to assume that a proportional
increase of $19,455 would occur for the 1.5 million beneficiaries enrolled in COHS managed care.
CHBRP assumes the two populations to be relatively similar and to have relatively similar benefit
coverage. In addition, it seems likely that there would also be some additional increase for the 1.5 million
Medi-Cal beneficiaries with health insurance through the FFS program. However, the similarity of this
population with the group enrolled in DMHC-regulated plans is unknown and their benefit coverage may
differ, so the exact amount of such an increase is unknown.
Enrollee Expenses
SB 221related changes in enrollee expenses for covered benefits and enrollee expenses for noncovered
benefits vary by market segment. Such changes are related to the number of enrollees (see Table 4 and
Table 5), with health insurance that would be subject to SB 221 and expected to use the relevant
treatments during the year after enactment. As would be expected, some enrollees using newly compliant
benefit coverage would incur some cost sharing,
Although enrollees with newly compliant benefit coverage may have paid for some treatments without SB
221, CHBRP cannot estimate the frequency with which such situations may have occurred and so cannot
estimate the total expense such situations might have incurred. Postmandate, such expenses would be
gone, though enrollees with newly compliant benefit coverage might, postmandate, pay for some
treatments for which coverage is denied (through utilization management review), as some enrollees who
always had compliant benefit coverage may have done before SB 221 and may continue to do
postmandate. Again, CHBRP cannot estimate the frequency with which such situations might occur, and
or the total expense such situations might incur.
Potential Cost Offsets or Savings in the First 12 Months After Enactment
CHBRP anticipates no measurable cost offsets or savings during the first 12 months after
implementation.
Postmandate Administrative Expenses and Other Expenses
CHBRP estimates that the increase in administrative costs of DMHC-regulated plans and/or CDI-
regulated policies will remain proportional to the increase in premiums. All health plans and insurers
Analysis of California Senate Bill 221
Current as of April 3, 2017 www.chbrp.org 28
include a component for administration and profit in their premiums. CHBRP assumes that the
administrative cost portion of premiums is unchanged.
Assuming that the impacts associated with SB 221 would be similar for COHS and the FFS program,
CHBRP would similarly expect the changes to have no measurable impact on those programs’
administrative costs.
Other Considerations for Policymakers
In addition to the impacts a bill may have on benefit coverage, utilization, and cost, related considerations
for policymakers are discussed below.
Postmandate Changes in the number of uninsured persons23
Because the change in average premiums does not exceed 1% for any market segment (see Table 5),
CHBRP would expect no measurable change in the number of uninsured persons due to the enactment
of SB 221.
Changes in public program enrollment
CHBRP estimates that the mandate would produce no measurable impact on enrollment in publicly
funded insurance programs due to the enactment of SB 221.
How Lack of Benefit Coverage Results in Cost Shifts to Other Payers
CHBRP assumes that a limited number of enrollees without benefit coverage paid for some or all of the
relevant treatments themselves, but that others did without. Therefore, SB 221 would not shift costs from
any other payers.
23 See also CHBRP’s Criteria and Methods for Estimating the Impact of Mandates on the Number of Uninsured,
available at www.chbrp.org/analysis_methodology/cost_impact_analysis.php.
Analysis of California Senate Bill 221
Current as of April 3, 2017 www.chbrp.org 29
Table 4. Baseline Per Member Per Month Premiums and Total Expenditures by Market Segment, California, 2018
DMHC-Regulated
CDI-Regulated
Privately Funded Plans
(by Market) (a)
Publicly Funded Plans
Privately Funded Plans
(by Market) (a)
Large
Group
Small
Group
Individual
CalPERS
HMOs (b)
MCMC
(Under 65)
(c)
MCMC
(65+) (c)
Large
Group
Small
Group
Individual
Total
Enrollee counts
Total enrollees in
plans/policies
subject to state
mandates (d)
9,128,000
3,163,000
2,379,000
884,000
7,192,000
644,000
276,000
145,000
237,000
24,048,000
Total enrollees in
plans/policies
subject to SB 221
9,128,000
3,163,000
2,379,000
884,000
7,192,000
644,000
276,000
145,000
237,000
24,048,000
Premiums
Average portion of
premium paid by
employer
$456.42
$324.76
$0.00
$460.43
$257.00
$751.00
$527.06
$433.40
$0.00
$97,688,732,000
Average portion of
premium paid by
employee
$115.59
$149.62
$469.56
$115.11
$0.00
$0.00
$166.32
$157.88
$423.05
$34,995,304,000
Total premium
$572.01
$474.38
$469.56
$575.54
$257.00
$751.00
$693.38
$591.28
$423.05
$132,684,037,000
Enrollee expenses
for covered benefits
(deductibles,
copays, etc.)
$44.11
$103.11
$126.07
$31.49
$0.00
$0.00
$115.39
$166.25
$75.74
$13,565,623,000
Enrollee expenses
for noncovered
benefits (e)(f)
Total
expenditures
$616.12
$577.49
$595.64
$607.03
$257.00
$751.00
$808.77
$757.53
$498.79
$146,249,664,000
Source: California Health Benefits Review Program, 2017.
Notes: (a) Includes enrollees with grandfathered and nongrandfathered health insurance, both on Covered California and outside the exchange.
(b) As of September 2016, 57% of CalPERS HMO members were state retirees under age 65, state employees or their dependents. CHBRP assumes the same
ratio for 2018.
Analysis of California Senate Bill 221
Current as of April 3, 2017 www.chbrp.org 30
(c) Medi-Cal Managed Care Plan expenditures for members over 65 include those who also have Medicare coverage. This population does not include enrollees
in COHS.
(d) This population includes both persons who obtain health insurance using private funds (group and individual) and through public funds (e.g., CalPERS HMOs,
Medi-Cal Managed Care Plans).Only those enrolled in health plans or policies regulated by the DMHC or CDI are included. Population includes all enrollees in
state-regulated plans or policies aged 0 to 64 years, and enrollees 65 years or older covered by employer-sponsored health insurance.
(e) Includes only those expenses that are paid directly by enrollees or other sources to providers for services related to the mandated benefit that are not currently
covered by insurance. This only includes those expenses that will be newly covered, postmandate. Other components of expenditures in this table include all
health care services covered by insurance.
(f) Although enrollees with newly compliant benefit coverage may have paid for some treatments at baseline, CHBRP cannot estimate the frequency with which
such situations may have occurred or and so cannot estimate the total expense such situations might have incurred. Postmandate, such expenses would be gone,
though enrollees with newly compliant benefit coverage might, postmandate, pay for some treatments for which coverage is denied (through utilization
management review), as some enrollees who always had compliant benefit coverage may have done before SB 221 and may continue to do, postmandate. Again,
CHBRP cannot estimate the frequency with which such situations might occur, and or the total expense such situations might incur.
Key: CalPERS HMOs = California Public Employees’ Retirement System Health Maintenance Organizations; CDI = California Department of Insurance; COHS =
County Organized Health Systems; DMHC = Department of Managed Health Care; MCMC = Medi-Cal Managed Care.
Analysis of California Senate Bill 221
Current as of April 3, 2017 www.chbrp.org 31
Table 5. Postmandate Per Member Per Month Premiums and Total Expenditures by Market Segment, California, 2018
DMHC-Regulated
CDI-Regulated
Privately Funded Plans
(by Market) (a)
Publicly Funded Plans
Privately Funded Plans
(by Market) (a)
Large
Group
Small
Group
Individual
CalPERS
HMOs (b)
MCMC
(Under
65) (c)
MCMC
(65+) (c)
Large
Group
Small
Group
Individual
Total
Enrollee counts
Total enrollees in
plans/policies
subject to state
mandates (d)
9,128,000
3,163,000
2,379,000
884,000
7,192,000
644,000
276,000
145,000
237,000
24,048,000
Total enrollees in
plans/policies
subject to SB 221
9,128,000
3,163,000
2,379,000
884,000
7,192,000
644,000
276,000
145,000
237,000
24,048,000
Premiums
Average portion of
premium paid by
employer
$0.0000
$0.0000
$0.0000
$0.0001
$0.0011
$0.0011
$0.0000
$0.0000
$0.0000
$104,000
Average portion of
premium paid by
employee
$0.0000
$0.0000
$0.0003
$0.0000
$0.0000
$0.0000
$0.0000
$0.0000
$0.0000
$10,000
Total premium
$0.0000
$0.0000
$0.0003
$0.0001
$0.0011
$0.0011
$0.0000
$0.0000
$0.0000
$114,000
Enrollee expenses
for covered benefits
(deductibles,
copays, etc.)
$0.0000
$0.0000
$0.0000
$0.0000
$0.0000
$0.0000
$0.0000
$0.0000
$0.0000
$1,000
for noncovered
benefits (e)(f)
----
Total expenditures
$0.0000
$0.0000
$0.0002
$0.0000
$0.0011
$0.0011
$0.0000
$0.0000
$0.0000
$115,000
Percent change
Premiums
0.0000%
0.0000%
0.0001%
0.0000%
0.0004%
0.0001%
0.0000%
0.0000%
0.0000%
0.0001%
Total
expenditures
0.0000%
0.0000%
0.0000%
0.0000%
0.0004%
0.0001%
0.0000%
0.0000%
0.0000%
0.0001%
Source: California Health Benefits Review Program, 2017.
Notes: (a) Includes enrollees with grandfathered and nongrandfathered health insurance, inside and outside the exchange.
(b) As of June 1, 2016, 58.82% of CalPERS members were state retirees, state employees, or their dependents. CHBRP assumes the same ratio for 2018.
Analysis of California Senate Bill 221
Current as of April 3, 2017 www.chbrp.org 32
(c) Medi-Cal Managed Care Plan expenditures for members over 65 include those who are also Medicare beneficiaries. This population does not include enrollees
in COHS.
(d) This population includes both persons who obtain health insurance using private funds (group and individual) and through public funds (e.g., CalPERS HMOs,
Medi-Cal Managed Care Plans). Only those enrolled in health plans or policies regulated by the DMHC or CDI are included. Population includes all enrollees in
state-regulated plans or policies aged 0 to 64 years, and enrollees 65 years or older covered by employer-sponsored health insurance.
(e) Includes only those expenses that are paid directly by enrollees or other sources to providers for services related to the mandated benefit that are not currently
covered by insurance. This only includes those expenses that will be newly covered, postmandate. Other components of expenditures in this table include all
health care services covered by insurance.
(f) Although enrollees with newly compliant benefit coverage may have paid for some treatments at baseline, CHBRP cannot estimate the frequency with which
such situations may have occurred or and so cannot estimate the total expense such situations might have incurred. Postmandate, such expenses would be gone,
though enrollees with newly compliant benefit coverage might, postmandate, pay for some treatments for which coverage is denied (through utilization
management review), as some enrollees who always had compliant benefit coverage may have done before SB 221 and may continue to do, postmandate. Again,
CHBRP cannot estimate the frequency with which such situations might occur, and or the total expense such situations might incur.
Key: CalPERS HMOs = California Public Employees’ Retirement System Health Maintenance Organizations; CDI = California Department of Insurance; COHS =
County Organized Health Systems; DMHC = Department of Managed Health Care; MCMC = Medi-Cal Managed Care.
Analysis of California Senate Bill 221
Current as of April 3, 2017 www.chbrp.org 33
PUBLIC HEALTH IMPACTS
SB221 would mandate coverage of treatments to repair or ameliorate maldistributions of body fat caused
by HIV associated lipodystrophy syndrome for enrollees in DMHC-regulated plans and CDI-regulated
policies, including Medi-Cal beneficiaries, as well as for Medi-Cal beneficiaries with health insurance
through a county organized health system (COHS) managed care program or Medi-Cal’s fee-for-service
(FFS) program.
Analytic Approach
As noted in the Benefit Coverage, Cost, and Utilization section, although SB 221 is an exception
(because it would alter the Welfare & Institutions Code as well), the benefit coverage of the 3 million
Medi-Cal beneficiaries associated with COHS and FFS are not commonly subject to the proposed
legislation CHBRP considers (because neither is subject to the California Health & Safety Code or the
California Insurance Code, which regulate DMHC-regulated plans and CDI-regulated policies). The
analysis which follows, unless otherwise specified, is and relevant to the 24 million Californians enrolled
in a plan or policy regulated by DMHC or CDI (a figure with does includes 7.8 million Medi-Cal
beneficiaries enrolled in DMHC-regulated plans).
The public health impact analysis includes estimated impacts in the short term (within 12 months of
implementation) and in the long term (beyond the first 12 months postmandate). This section estimates
the short-term impact24 of SB 221 on the burden of lipodystrophy-associated morbidity, quality of life, and
financial burden among patients with lipodystrophy. See the Long-Term Impacts section for a discussion
of economic loss, and quality of life improvements for enrollees being treated for HIV infection.
Estimated Public Health Outcomes
As described more fully in the Background section of this report, lipodystrophy is not considered to be a
clinically life-threatening condition; however, it can be painful or restrictive and potentially result in quality-
of-life deficits (Collins et al., 2000; Guaraldi et al., 2007, 2008; Power et al., 2003; Rajagopalan et al.,
2008). Treatments for lipodystrophy are not curative, but may prevent, correct, or ameliorate the burden
of physical changes caused by underlying metabolic dysfunction characteristic of lipodystrophy.
As presented in the Medical Effectiveness section, treatments for the effects of HIV associated
lipoatrophy or lipohypertrophy include reconstructive surgery, prescription medications, and switching
antiretroviral regimens. The benefits of switching antiretroviral regimens are being realized by Californians
independent of whether SB 221 is enacted because the antiretroviral drugs that are most likely to cause
lipoatrophy are no longer routinely prescribed. Evidence from several studies suggests that use of certain
treatments (i.e., dermal fillers, autologous fat transplantation, liposuction, and tesamorelin) may result in
short-term relief from symptoms as well as improvements in physical appearance and quality of life. Given
that CHBRP estimates a postmandate increase in new users for the drug and medical surgical
lipodystrophy treatments included in the analysis (as described in the Benefit Coverage, Utilization, and
Cost Impacts section), it stands to reason that, if enacted, the amendments proposed in SB 221 would
result in a reduction of the physical and psychological burden of lipodystrophy among the HIV-positive
population in California, and produce short-term health and quality-of-life improvements such as improved
24 CHBRP defines short-term impacts as changes occurring within 12 months of bill implementation.
Analysis of California Senate Bill 221
Current as of April 3, 2017 www.chbrp.org 34
range of motion or satisfaction with appearance, for the 15 enrollees with HIV associated lipodystrophy
who would newly use these medically effective treatments.
In the first year postmandate, CHBRP estimates that there would be new use of medical/surgical and
drug treatments for lipodystrophy, resulting in a reduction of outward lipodystrophy symptoms and
associated health and quality of life improvements among those new users. However, CHBRP projects no
measurable public health impact at the population level due to the small estimated increase in enrollees
(15 individuals) who would use medical/surgical and drug treatments for lipodystrophy.
Analysis of California Senate Bill 221
Current as of April 3, 2017 www.chbrp.org 35
LONG-TERM IMPACTS
In this section, CHBRP estimates the long-term impact25 of SB 221, which CHBRP defines as impacts
occurring beyond the first 12 months after implementation. These estimates are qualitative and based on
the existing evidence available in the literature. CHBRP does not provide quantitative estimates of long-
term impacts because of unknown improvements in clinical care, changes in prices, implementation of
other complementary or conflicting policies, and other unexpected factors.
As noted in the Background section and in the Benefit Coverage, Cost, and Utilization section, the
prevalence of HIV associated lipodystrophy appears to have drastically declined, currently present in less
than 1% of California’s HIV+ enrollees in plans and policies regulated by DMHC or CDI. In the long term,
CHBRP expects that the prevalence of HIV associated lipodystrophy will continue to decline. In part, this
is due to discontinued use of antiretroviral therapies that produce lipoatrophy following the introduction of
less lipotoxic antiretroviral medications in the early 2000s (Nguyen et al., 2008). Therefore, CHBRP
assumes that the demand for lipoatrophy treatments, such as dermal fillers and autologous fat
transplantation, is likely to continue to decrease over time, as will their relative impact on the overall
burden of lipodystrophy symptoms among HIV-positive populations in California.
Long-Term Utilization and Cost Impacts
As the prevalence of HIV associated lipodystrophy appears to have declined along with use of early
antiretroviral drugs (considerably fewer new diagnoses since the 1990s), there may be a shrinking
number of persons for whom the treatments are medically necessary. This suggests that the utilization
and cost impacts projected in this analysis for the first year after implementation of SB 221 would not be
constant, rather, they would likely decline over time.
Long-Term Public Health Impacts
Some interventions in proposed mandates provide immediate measurable impacts (e.g., maternity service
coverage or acute care treatments), whereas other interventions may take years to make a measurable
impact (e.g., coverage for tobacco cessation or vaccinations). When possible, CHBRP estimates the long-
term effects (beyond 12 months postmandate) to the public’s health that would be attributable to the
mandate.
For the population that remains affected by lipodystrophy, there is no treatment that cures the underlying
metabolic dysfunction causing abnormal fat distribution; rather, as evidenced in the Medical Effectiveness
section, treatments may, to varying degrees, provide short-term relief from the burden of lipoatrophy- or
lipohypertrophy-related symptoms and result in potential improvements in quality of life.
However, to the extent that treatments for lipodystrophy symptoms may be used, there is little or
insufficient evidence of long-term effectiveness for lipodystrophy treatments. In particular, one form of
lipohypertrophy, “buffalo hump,” has been found to recur within 1 year in 30% to 100%26 of cases treated
with liposuction (Hultman et al., 2007). Similarly, although there are no trials evaluating safety and use of
tesamorelin in the long term, short-term research suggests that patients using tesamorelin to control
25 See also CHBRP’s Criteria and Guidelines for the Analysis of Long-Term Impacts on Healthcare Costs and Public
Health, available at http://www.chbrp.org/analysis_methodology/cost_impact_analysis.php.
26 Personal communication, E. Murphy, March 14, 2017.
Analysis of California Senate Bill 221
Current as of April 3, 2017 www.chbrp.org 36
lipodystrophy-associated abdominal fat gain typically regain fat after treatment ends (Moyle et al., 2010).
Synthetic dermal fillers have been shown to correct facial lipoatrophy up through 2 years (Jagdeo et al.,
2015); however, there is insufficient evidence of effectiveness in the long term.
In addition, there are several reasons why patients would discontinue use of treatments for lipodystrophy
over time. In the case of tesamorelin, patients may not be willing to receive daily injections indefinitely to
control a condition (lipohypertrophy) that is not life-threatening.27 Surgical treatments are invasive, and
even when covered by insurance, patients may be reluctant to have them if they are enrolled in health
plans that require high cost sharing for surgery. Considering that some patients may need to repeat or
utilize multiple treatments, the financial burden associated with out-of-pocket costs could be a deterrent to
treatment over time (Hornberger et al., 2009). Finally, as patients age, the demand for treatments may
decrease as the effects of both lipoatrophy and lipohypertrophy to some extent mimic common
physiologic changes associated with aging (Guaraldi et al., 2014).
In the case of SB 221, CHBRP estimates that utilization of treatments for HIV associated lipodystrophy
beyond 12 months will decrease due to the decline in incidence of lipodystrophy among the HIV positive
population. Therefore, any impacts of treatment for lipodystrophy (i.e., reductions in lipodystrophy-
associated morbidity or quality of life improvements) on the health of HIV positive persons in California
may decrease over time concurrent with changing incidence.
Impacts on Economic Loss
Economic loss associated with disease is generally presented in the literature as an estimation of the
value of the YPLL in dollar amounts (i.e., valuation of a population’s lost years of work over a lifetime). In
addition, morbidity associated with the disease or condition of interest can also result in lost productivity
by causing a worker to miss days of work due to illness or acting as a caregiver for someone else who is
ill.
Persons living with lipodystrophy report a range of quality-of-life deficits, including social isolation due to
the outward appearance of illness. Anecdotal evidence from qualitative studies has linked the visible body
alterations cause by lipodystrophy to job loss and decreased productivity, including missed or reduced
opportunities for advancement (Collins et al., 2000; Power et al., 2003). Additionally, among a cohort of
HIV positive persons living in the United Kingdom, Ibrahim et al. found that participants living with visible
appearance alterations associated with their HIV status had twice the odds of being unemployed
compared with participants who exhibited no outward signs of infection (Ibrahim et al., 2008).
To the extent that medically effective treatments for lipodystrophy may reduce recognizable, physical
indicators of HIV infection, the long-term impacts of lipodystrophy on unemployment and work loss may
be reduced for those newly receiving treatments due to the coverage extended in SB 221.
27 Personal communication, E. Murphy, March 14, 2017.
Analysis of California Senate Bill 221
Current as of April 3, 2017 www.chbrp.org A-1
APPENDIX A TEXT OF BILL ANALYZED
On February 3, 2017, the California Senate Committee on Health requested that CHBRP analyze SB
221.
CALIFORNIA LEGISLATURE20172018 REGULAR SESSION
SENATE BILL
No. 221
Introduced by Senator Wiener
(Coauthors: Senators Atkins and Galgiani)
February 02, 2017
An act to add Section 1367.47 to the Health and Safety Code, to add Section 10123.92 to the
Insurance Code, and to add Section 14132.04 to the Welfare and Institutions Code, relating to
health care coverage.
LEGISLATIVE COUNSEL'S DIGEST
SB 221, as introduced, Wiener. Health care coverage: lipodystrophy syndrome.
Existing law, the Knox-Keene Health Care Service Plan Act of 1975, provides for the licensure
and regulation of health care service plans by the Department of Managed Health Care and
makes a willful violation of the act a crime. Existing law also provides for the regulation of
health insurers by the Department of Insurance. Existing law requires health care service plan
contracts and health insurance policies to provide coverage for specified benefits.
This bill would require health care service plan contracts and health insurance policies issued,
amended, renewed, or delivered on or after January 1, 2018, to include coverage for medical or
drug treatments to correct or repair disturbances of body composition caused by human
immunodeficiency virus (HIV) associated lipodystrophy syndrome, including, but not limited to,
reconstructive surgery, such as suction assisted lipectomy, other restorative procedures and
dermal injections or fillers for reversal of facial lipoatrophy syndrome, as provided. Because a
Analysis of California Senate Bill 221
Current as of April 3, 2017 www.chbrp.org A-2
willful violation of the bill’s provisions by a health care service plan would be a crime, it would
impose a state-mandated local program.
Existing law provides for the Medi-Cal program, which is administered by the State Department
of Health Care Services and under which qualified low-income persons receive health care
benefits. The Medi-Cal program is, in part, governed and funded by federal Medicaid provisions.
Existing law provides for coverage of certain medical services, including, but not limited to,
physician, hospital or clinic outpatient, surgical center, optometric, chiropractic, psychology,
occupational therapy, physical therapy, speech therapy, and audiology under the Medi-Cal
program.
This bill would require the Medi-Cal program to cover medical or drug treatments to correct or
repair disturbances of body composition caused by HIV associated lipodystrophy syndrome,
including, but not limited to, reconstructive surgery, such as suction assisted lipectomy, other
restorative procedures and dermal injections or fillers for reversal of facial lipoatrophy
syndrome, as provided.
The California Constitution requires the state to reimburse local agencies and school districts for
certain costs mandated by the state. Statutory provisions establish procedures for making that
reimbursement.
This bill would provide that no reimbursement is required by this act for a specified reason.
DIGEST KEY
Vote: majority Appropriation: no Fiscal Committee: yes Local Program: yes
BILL TEXT
THE PEOPLE OF THE STATE OF CALIFORNIA DO ENACT AS FOLLOWS:
SECTION 1.
Section 1367.47 is added to the Health and Safety Code, to read:
1367.47.
(a) A health care service plan contract issued, amended, renewed, or delivered on or after
January 1, 2018, shall include coverage for medical or drug treatments to correct or repair
disturbances of body composition caused by human immunodeficiency virus (HIV) associated
lipodystrophy syndrome, including, but not limited to, reconstructive surgery, such as suction
assisted lipectomy, other restorative procedures and dermal injections or fillers for reversal of
facial lipoatrophy syndrome. Coverage shall be subject to a statement from a treating provider
that the treatment is necessary for correcting, repairing, or ameliorating the effects of HIV
associated lipodystrophy syndrome.
Analysis of California Senate Bill 221
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(b) This section shall not apply to accident-only, specified disease, hospital indemnity, Medicare
supplement, dental-only, or vision-only health care service plan contracts.
SEC. 2.
Section 10123.92 is added to the Insurance Code, to read:
10123.92.
(a) A health insurance policy issued, amended, renewed, or delivered on or after January 1, 2018,
shall include coverage for medical or drug treatments to correct or repair disturbances of body
composition caused by human immunodeficiency virus (HIV) associated lipodystrophy
syndrome, including, but not limited to, reconstructive surgery, such as suction assisted
lipectomy, other restorative procedures and dermal injections or fillers for reversal of facial
lipoatrophy syndrome. Coverage shall be subject to a statement from a treating provider that the
treatment is necessary for correcting, repairing, or ameliorating the effects of HIV associated
lipodystrophy syndrome.
(b) This section shall not apply to accident-only, specified disease, hospital indemnity,
CHAMPUS supplement, TRI-CARE supplement, Medicare supplement, dental-only, or vision-
only health insurance policies.
SEC. 3.
Section 14132.04 is added to the Welfare and Institutions Code, to read:
14132.04.
(a) A covered Medi-Cal benefit shall include medical or drug treatments to correct or repair
disturbances of body composition caused by human immunodeficiency virus (HIV) associated
lipodystrophy syndrome, including, but not limited to, reconstructive surgery, such as suction
assisted lipectomy, other restorative procedures and dermal injections or fillers for reversal of
facial lipoatrophy syndrome. Coverage shall be subject to a statement from a treating provider
that the treatment is necessary for correcting, repairing, or ameliorating the effects of HIV
associated lipodystrophy syndrome.
(b) This section shall be implemented only to the extent permitted by federal law.
(c) Notwithstanding Chapter 3.5 (commencing with Section 11340) of Part 1 of Division 3 of
Title 2 of the Government Code, the department may implement the provisions of this section by
means of all-county letters, provider bulletins, or similar instructions, without taking further
regulatory action.
(d) The department shall seek any necessary federal approval for federal financial participation
and coverage of services in this section under the Medi-Cal program.
SEC. 4.
No reimbursement is required by this act pursuant to Section 6 of Article XIII B of the California
Constitution because the only costs that may be incurred by a local agency or school district will
be incurred because this act creates a new crime or infraction, eliminates a crime or infraction, or
Analysis of California Senate Bill 221
Current as of April 3, 2017 www.chbrp.org A-4
changes the penalty for a crime or infraction, within the meaning of Section 17556 of the
Government Code, or changes the definition of a crime within the meaning of Section 6 of
Article XIII B of the California Constitution.
Analysis of California Senate Bill 221
Current as of April 3, 2017 www.chbrp.org B-1
APPENDIX B LITERATURE REVIEW METHODS
Appendix B describes methods used in the medical effectiveness literature review conducted for this
report. A discussion of CHBRP’s system for grading evidence, as well as lists of MeSH Terms, publication
types, and keywords, follows.
Studies of treatments for HIV associated lipodystrophy were identified through searches of PubMed, the
Cochrane Library, Web of Science, EconLit, Business Source Complete, the Cumulative Index of Nursing
and Allied Health Literature (CINAHL), and PsycINFO. Websites maintained by the following
organizations that produce and/or index meta-analyses and systematic reviews were also searched: the
Agency for Healthcare Research and Quality (AHRQ), the International Network of Agencies for Health
Technology Assessment (INAHTA), the National Health Service (NHS) Centre for Reviews and
Dissemination, the National Institute for Health and Clinical Excellence (NICE), and the Scottish
Intercollegiate Guideline Network.
The search was limited to abstracts of studies published in English. The search was limited to studies
published from 2002 to present. CHBRP relied on a systematic review published in 2011 for findings from
studies on growth hormone and a synthetic analog of growth hormone (tesamorelin) published prior to
2011. CHBRP relied on a systematic review published in 2015 for findings from studies on fillers and
autologous fat transplantation published prior to 2015. CHBRP relied on two systematic reviews
published in 2013 for findings from studies on antiretroviral therapy (ART) drugs published prior to 2013.
CHBRP relied on a systematic review published in 2010 for findings from studies on insulin sensitizing
drugs published prior to 2010.
Reviewers screened the title and abstract of each citation retrieved by the literature search to determine
eligibility for inclusion. The reviewers acquired the full text of articles that were deemed eligible for
inclusion in the review and reapplied the initial eligibility criteria.
Of the 338 articles found in the literature review, 50 were reviewed for potential inclusion in this report on
SB 221, and a total of 20 studies were included in the medical effectiveness review for this report. The
other articles were eliminated because they did not focus on HIV associated lipodystrophy, were of poor
quality, or did not report findings from clinical research studies.
Evidence Grading System
In making a “call” for each outcome measure, the medical effectiveness lead and the content expert
consider the number of studies as well the strength of the evidence. Further information about the criteria
CHBRP uses to evaluate evidence of medical effectiveness can be found in CHBRP’s Medical
Effectiveness Analysis Research Approach.28 To grade the evidence for each outcome measured, the
team uses a grading system that has the following categories:
Research design;
Statistical significance;
Direction of effect;
28 Available at: www.chbrp.org/analysis_methodology/docs/medeffect_methods_detail.pdf.
Analysis of California Senate Bill 221
Current as of April 3, 2017 www.chbrp.org B-2
Size of effect; and
Generalizability of findings.
The grading system also contains an overall conclusion that encompasses findings in these five domains.
The conclusion is a statement that captures the strength and consistency of the evidence of an
intervention’s effect on an outcome. The following terms are used to characterize the body of evidence
regarding an outcome:
Clear and convincing evidence;
Preponderance of evidence;
Limited evidence
Conflicting evidence; and
Insufficient evidence.
A grade of clear and convincing evidence indicates that there are multiple studies of a treatment and that
the large majority of studies are of high quality and consistently find that the treatment is either effective
or not effective.
A grade of preponderance of evidence indicates that the majority of the studies reviewed are consistent in
their findings that treatment is either effective or not effective.
A grade of limited evidence indicates that the studies had limited generalizability to the population of
interest and/or the studies had a fatal flaw in research design or implementation.
A grade of conflicting evidence indicates that although some studies included in the medical effectiveness
review find that a treatment is effective, a similar number of studies of equal quality suggest the treatment
is not effective.
A grade of insufficient evidence indicates that there is not enough evidence available to know whether or
not a treatment is effective, either because there are too few studies of the treatment or because the
available studies are not of high quality. It does not indicate that a treatment is not effective.
The search terms used to locate studies relevant to SB 221 were as follows:
Major MeSH terms used to search PubMed
HIV Associated Lipodystrophy Syndrome [Majr]
Subheadings used with above heading:
/surgery
/rehabilitation
/drug therapy
/therapy
/economics
/statistics and numerical data
/ethnology
/epidemiology
Age Factors
Costs and Cost Analysis [EXP]
Epidemiologic Factors [EXP[
Outcome Assessment [EXP]
Vital Statistics [EXP]
Analysis of California Senate Bill 221
Current as of April 3, 2017 www.chbrp.org B-1
Keywords used to search Embase, Cochrane Library, Web of Science, and relevant websites:
“HIV Associated Lipodystrophy”
(HIV AND Lipodystrophy) in Title
Age Factors
Comorbidities
Cost or Costs
Demand
Drug Therapy
Economics
Epidemiologic Factors or Epidemiology
Ethnicity
Morbidity
Mortality
Outcome*
Prevalence
Quality of Life
Racial Disparities
Savings
Statistics
Supply
Surgery
Therapy
Utilization
Vital Statistics
* = Truncation
Analysis of California Senate Bill 221
Current as of April 3, 2017 www.chbrp.org C-1
APPENDIX C COST IMPACT ANALYSIS: DATA
SOURCES, CAVEATS, AND ASSUMPTIONS
The cost analysis in this report was prepared by the members of the cost team, which consists of CHBRP
task force members and contributors from the University of California, Los Angeles, and the University of
California, Davis, as well as the contracted actuarial firms, PricewaterhouseCoopers (PwC).29
Information on the generally used data sources and estimation methods, as well as caveats and
assumptions generally applicable to CHBRP’s cost impacts analyses are available at CHBRP’s website.30
This appendix describes any analysis-specific data sources, estimation methods, caveats and
assumptions used in preparing this cost impact analysis.
Analysis Specific Caveats and Assumptions
This subsection discusses the caveats and assumptions relevant to the analysis of SB 221.
The population with health insurance that would be subject to SB 221 includes enrollees by DMHC-
regulated commercial insurance plans (including plans with enrollees associated with CalPERS and
Medi-Cal and CDI-regulated policies and would further impact the benefit coverage of Medi-Cal
beneficiaries whose health insurance is through the COHS and FFS programs). Health plans and insurers
could comply with this mandate) as part of their basic benefit package.
CHBRP assumed that the mandate would not impact any forms of cost sharing, such as deductibles,
copays, and coinsurance. It is also assumed that the bill would not affect plan/insurer methods of
utilization management that may impact postmandate coverage of medical and drug treatments between,
such as use of prior authorization requirements and medical review for medical treatments, and use of
formularies, tiered copayments, or mandatory generic substitutions for drug treatments.
Additionally, the following is a description of methodology and assumptions used to develop the estimates
of cost impacts:
For medical treatment of HIV associated lipodystrophy, Healthcare Common Procedure Coding
System (HCPCS) and Current Procedural Terminology (CPT) codes were identified with carrier
coverage guidelines and reviewed by a content expert. Additionally, for drug treatment of HIV
associated lipodystrophy, National Drug Codes (NDC) codes were identified using the Truven
Health Analytics Red Book™ and reviewed by a content expert.
The estimated unit cost per service of HIV associated lipodystrophy treatment services, both for
baseline and postmandate, used 2014 and 2015 MarketScan® Commercial Claims and
Encounters Database, which reflects the most recent periods that are available. Two years of
data were used to increase data credibility.
Because lipodystrophy treatments were similar between HIV and non-HIV members, unit cost per
service were analyzed using claims from members identified with lipodystrophy regardless of HIV
29 CHBRP’s authorizing statute, available at www.chbrp.org/docs/authorizing_statute.pdf, requires that CHBRP use a
certified actuary or “other person with relevant knowledge and expertise” to determine financial impact.
30 See 2017 Cost Impact Analyses: Data Sources, Caveats, and Assumptions, available at
www.chbrp.org/analysis_methodology/cost_impact_analysis.php.
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status. From the 2014 and 2015 MarketScan® Commercial Claims and Encounters Database,
utilization and unit cost information was developed for each service category.
Baseline unit costs were trended at 3.1% annual rate of increase from 2015 to 2017 based on
2016 medical CPI rate, for a total increase of 9.6% over the time period. Baseline drug cost was
trended at 6.5% annual rate of increase from 2014 to 2017 based on 2016 CPI rate, for a total
increase of 20.8%.
The analysis assumed that the unit cost per service do not change postmandate.
The analysis assumed that utilization rates per 1,000 enrollees change postmandate only due to
increased coverage.
Baseline utilization rates per 1,000 enrollees were developed based on MarketScan® data for
members diagnosed with HIV associated lipodystrophy. These members were identified by
isolating incurred claims containing lipodystrophy and HIV ICD-9 and ICD-10 diagnosis codes
between 2014 and 2015. Despite different treatments for those with lipoatrophy and those with
lipodeposition, ICD-9 and ICD-10 codes do not distinguish between these two conditions.
Prevalence assumptions were made for the population 65 and older, due to absence of
MarketScan® data for this segment. Kaiser Family Foundation estimates HIV prevalence for
Medicare beneficiaries to be 0.5%. Using the 0.5% HIV prevalence rate, CHBRP applied
lipodystrophy prevalence among HIV patients age 60 to 64 observed in Truven data to estimate
number of HIV- associated lipodystrophy patients 65 and older.
Carrier surveys were administered to estimate the percentage of enrollees who had HIV-
associated lipodystrophy treatment coverage in the baseline period.
In the baseline and postmandate period, all enrollees with HIV are assumed to have outpatient
drug coverage.
There are likely out-of-pocket cost savings to enrollees postmandate who were in plans not
compliant with SB221 and were paying for treatments out of pocket because their coverage was
denied. However, there are no data to suggest what the current prevalence is for HIV associated
lipodystrophy patients who pay for treatment out of pocket when treatment is denied and how
much they pay out of pocket. Thus, CHBRP is unable to determine out-of-pocket cost savings
estimates for these users.
Due to the elasticity of demand for lipodystrophy treatments, in the baseline period, the analysis
assumed individuals without coverage for treatments is 50% as likely to pay for treatment as
individuals with coverage for treatments unless they are enrolled in Medi-Cal. In the baseline
period, Medi-Cal individuals without coverage for treatments will not pay for treatments.
Determining Public Demand for the Proposed Mandate
This subsection discusses public demand for the benefits SB 221 would mandate. Considering the criteria
specified by CHBRP’s authorizing statute, CHBRP reviews public demand for benefits relevant to a
proposed mandate in two ways. CHBRP:
Considers the bargaining history of organized labor; and
Compares the benefits provided by self-insured health plans or policies (which are not regulated
by the DMHC or CDI and therefore not subject to state-level mandates) with the benefits that are
provided by plans or policies that would be subject to the mandate.
Analysis of California Senate Bill 221
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On the basis of conversations with the largest collective bargaining agents in California, CHBRP
concluded that unions currently do not include cost-sharing arrangements for description treatment or
service. In general, unions negotiate for broader contract provisions such as coverage for dependents,
premiums, deductibles, and broad coinsurance levels.
Among publicly funded self-insured health insurance policies, the preferred provider organization (PPO)
plans offered by CalPERS currently have the largest number of enrollees. The CalPERS PPOs currently
provide benefit coverage similar to what is available through group health insurance plans and policies
that would be subject to the mandate.
To further investigate public demand, CHBRP used the bill-specific coverage survey to ask carriers who
act as third-party administrators for (non-CalPERS) self-insured group health insurance programs
whether the relevant benefit coverage differed from what is offered in group market plans or policies that
would be subject to the mandate. The responses indicated that there were no substantive differences.
Analysis of California Senate Bill 221
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APPENDIX D INFORMATION SUBMITTED BY OUTSIDE
PARTIES