The Effect of Expanded Antiretroviral Treatment Strategies on the HIV Epidemic Among Men Who Have Sex With Men in San Francisco

HIV/AIDS Division, Department of Medicine, San Francisco General Hospital, California, USA.
Clinical Infectious Diseases (Impact Factor: 8.89). 04/2011; 52(8):1046-9. DOI: 10.1093/cid/cir085
Source: PubMed


(See editorial commentary by DeGruttola and Schooley on pages 1050–1052.)
Modeling of expanding antiretroviral treatment to all HIV-infected adults already in care in San Francisco predicts reductions in new HIV infection at 5 years of 59% among men who have sex with men. Addition of annual HIV testing for men who have sex with men to universal treatment decreases new infections by 76%.


Available from: Moupali Das
The Effect of Expanded
Antiretroviral Treatment Strategies
on the HIV Epidemic among Men
Who Have Sex with Men in San
Edwin D. Charlebois,
Moupali Das,
Travis C. Porco,
and Diane
V. Havlir
HIV/AIDS Division, Department of Medicine, San Francisco General Hospital, and
Center for AIDS Prevention Studies, Department of Medicine, University of
California, and
San Francisco Department of Public Health, and
Francis I. Proctor
Foundation for Research in Ophthalmology, Department of Epidemiology and
Biostatistics, University of California, San Francisco, California
(See editorial commentary by DeGruttola and Schooley on pages
Modeling of expanding antiretroviral treatment to all HIV-
infected adults already in care in San Francisco predicts re-
ductions in new HIV infection at 5 years of 59% among men
who have sex with men. Addition of annual HIV testing for
men who have sex with men to universal treatment decreases
new infections by 76%.
A model of annual testing and immediate initiation of anti-
retroviral therapy (ART) in South Africa predicted a dramatic
reduction in incidence of HIV infection [1]. In response, critics
highlighted the practical applicability of such an approach in
South Africa, and the debate about the optimum timing of ART
initiation continues. In San Francisco, which has a generalized
epidemic among men who have sex with men (MSM; 24%
prevalence), challenges exist but are far less significant than those
in South Africa. More than 72% of MSM report annual testing,
and .85% of MSM are aware of their HIV status. Linkage to
primary care is high (88%) even among individuals who receive
a diagnosis at a public health clinic [2]. Of most significance, the
San Francisco Department of Public Health estimates that 78%
of all known HIV-infected persons were receiving care in 2008
[3]. With the public health resources and political will to support
wide availability of antiretroviral medications, including Healthy
San Francisco, a city-wide public health insurance safety net,
high population-level rates of virologic suppression are achiev-
able. In the context of this setting and early 2009 guidelines for
starting ART at CD4 cell counts ,350, we sought to determine
the potential impact on incident HIV infection in the MSM
population of offering ART to all patients in care—a strategy
that maximizes the individual and public health benefit for those
already receiving care without requiring additional investment
in outreach and expanded HIV testing.
We developed an ordinary differential equation simula-
tion model for HIV testing and treatment among MSM in San
Francisco extending previous models [1, 4, 5]. We tested 3 ART
expansion strategies: (1) treatment of all individuals currently
receiving HIV care with CD4 cell counts ,500 cells/mm
; (2)
treatment of all individuals receiving care; and (3) intensified
annual HIV testing combined with treatment of all HIV-in-
fected persons (the full test-and-treat strategy). Inputs to the
model were based on comprehensive surveillance information
on prevalence and incidence of HIV infection, testing rates, and
treatment outcomes data available for San Francisco from the
local health department and electronic patient databases of the
San Francisco General Hospital outpatient HIV treatment
clinics that contain information on 95% of individuals known
to be HIV infected in San Francisco [6]. We stratified the
population of MSM according to risk groups, HIV status, CD4
cell count group, and treatment, as follows. We classified in-
dividuals as either uninfected or infected. Infected men, in turn,
are classified according to the untreated nadir CD4 cell count
into 1 of 4 stages: CD4 cell count .500 cells/mm
, CD4 cell
count of 350–500 cells/mm
, CD4 cell count of 200–350 cells/
, and CD4 cell count ,200 cells/mm
. Individuals in the
model may (1) have unknown serostatus and not be receiving
treatment; (2) have known HIV infection but not receiving
ART; (3) be receiving ART but not yet achieved suppression; or
(4) be receiving long-term antiretroviral therapy. Eighty per-
cent of individuals receiving long-term therapy were assumed
to have achieved durable virological suppression. Untreated
Received 8 October 2010; accepted 12 December 2010.
Correspondence: Edwin D. Charlebois, MPH, PhD, Center for AIDS Prevention Studies,
University of California, San Francisco, 50 Beale St, 13th Fl, San Francisco, CA 94105
Clinical Infectious Diseases 2011;52(8):1046–1049
Ó The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases
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DOI: 10.1093/cid/cir085
CID 2011:52 (15 April)
Page 1
individuals progress forward through successive HIV stages
according to rates estimated from previous studies [7]. In-
dividuals who have achieved virologic suppression proceed
through nadir CD4 cell count stages at a slower rate (zero in the
baseline scenario). Individuals in either the short-term in-
complete suppression classes have ongoing HIV progression
through stages at a rate intermediate between the untreated and
completely suppressed groups. The mean time between initia-
tion of therapy and achievement of full suppression was 3
Individuals with complete or incomplete suppression may stop
therapy at rates estimated from observed fractions of therapy
(mean of 1% per year). The rate of starting therapy (or restarting
therapy) depends on the HIV stage. Individuals with a CD4 cell
count ,200 are assumed to start therapy with a mean waiting
time of 3 months. The time to initiation of therapy for individuals
in other stages is assumed to be 3 months when a test-and-treat
program has been initiated and is longer otherwise. The rate of
stopping therapy was higher for individuals with incomplete
suppression than for individuals with complete virological sup-
pression. Finally, individuals undergo HIV testing at a rate of 1 test
per 3 years in the absence of a treatment program (and, thus,
transition from unknown status to known status) at this rate.
We assumed 2 risk groups (high and low) distinguished by
more unprotected contacts per unit time. The transmission
probability per uninfected contact was assumed to be 0.1[8].
Eighty percent of the population was assumed to be in the low-
risk group. The transmission probability was assumed to be
lower if the infected person was receiving treatment; we assumed
20% relative transmission for infected persons with incomplete
virological suppression and 1% for persons with complete vi-
rological suppression [9]. We assumed nonrandom mixing be-
tween the high- and low-risk groups, with a mixing parameter
of 0.6 ( 0 for completely random mixing to 1 for completely
positive assortative [like only with like] mixing). The number
of contacts per unit time and the mixing parameter were chosen to
give a prevalence of 0.24 in 2007, in agreement with data. Finally,
the total population at risk was assumed to be 67,000 and the mean
sexually active residence time to be 30 years [4].
We performed sensitivity analyses on key variable inputs
to assess model results variability by repeating model runs
with inflated and deflated inputs for single variable s chosen
from the range of likely values as estimated f rom the litera-
ture and clinic databases. Change in model results were
evaluated by calculating percent change in reduction in new
HIV i nfections.
All 3 expanded ART strategies resulted in reduction of pre-
dicted prevalence of HIV infection and new HIV infections,
compared with the 2008–2009 standard of care of starting ART
for HIV-infected persons with CD4 cell counts ,350 cells/mm
(see Table 1). Significant reductions in new HIV infections
were predicted in as early as 5 years from the implementation
of expanded ART for all 3 strategies. The test-and-treat all
strategy had the largest effect of the 3 expanded ART strategies,
eventually doubling the number of new HIV infections averted,
compared with the least ambitious strategy. However, signifi-
cant gains in averting new HIV infections were seen for both
of the expanded ART strategies (,500 and treat all) that in-
volved changing ART initiation practices without implement-
ing additional HIV testing and linkage to care programs. The
model does not predict elimination o f the HIV epidemic
among MSM in San Francisco (reduction of prevalence and
incidence of HIV infection to negligible or zero levels). How-
ever, at 20 years, the test-and-treat strategy predicts reduction
in prevalence of HIV infection among MSM in San Francisco
from 26.2% to 12.8%, greater than reducing the prevalence of
HIV infection by half in the absence of changes in 2008–2009
ART practices.
The model was most sensitive to assumptions of the effec-
tiveness of ART in reducing HIV transmission probabilities. A
reduction in the effectiveness of ART in reducing HIV trans-
mission from 99% to 90% resulted in a .30% reduction in the
percentage of new HIV infections averted over 20 years. The
model was less sensitive to changes in the proportion of in-
dividuals who are able to achieve virological suppression, with
a 10% decrease in the proportion achieving suppression re-
sulting in a ,10% decrease in the percentage of new infections
averted. Other model input parameters evaluated in sensitivity
analyses (treatment cessation rates, mortality rates, in-
fectiousness with incomplete viral suppression, testing rates, and
the proportion in the high-risk group) demonstrated similar
relative effects between the strategies over the range of likely
San Francisco is one of the original epicenters of the HIV
epidemic and remains the site of one of the largest concen-
trated epidemics of HIV infection in the United States, with
a 24% prevalence among MSM, exceeding levels reported in
other concentrated epidemics, such as MSM in New York City
and African-American men in Washington, DC [10]. Despite
advancements in treatment a nd expanded outreach efforts,
600 incident HIV infections occurred in San Francisco in
2008 [11]. New strategies of combination prevention that
include both behavioral and biomedical interventions are t hus
needed [12].
Our model demonstrates that expansion of ART to those
already in care with CD4 cell counts ,500 cells/mm
or at any
CID 2011:52 (15 April)
Page 2
CD4 cell count is likely to significantly reduce the number of
future HIV infections. Further reductions could be gained by
the addition of routine annual testing and linkage to care.
These findings extend other models of San Francisco a nd
Vancouver by anchoring the analysis to empirical data re-
garding engagement in care and the new Department of
Health & Human Services (DHHS) guidelines for A RT initi-
ation [13].
It is instructive to contrast our findings to those of a recent
modeling analysis of the HIV epidemic in Washington, DC. Our
model predicts greater reductions in new HIV infections,
compared with analysis from Washington, DC. Although the
deterministic model with its inherent limitations differed from
the stochastic simulation model used by Walensk y et al may
have contributed to these differences, the critical difference is
that only 50% of pe rsons in the DC model are linked to care
after a positive HIV test result [14]. Indeed, these authors and
other modeling reports from South Africa emphasize the
importance of linkage to care as a limiting factor in ART
expansion strategies reducing incident HIV infections [15].
When the DC model includes nearly complete linkage to care,
results of the models converge. Testing and linkage to care are
appropriately one of the highest public health priorities in
populations with high prevalence worldwide. In San Fran-
cisco, with the high rates of HIV testing and linkage to care,
we have the opportunity to reduce HIV t ransmission by ex-
panding ART to those already receiving care while we
determine the most cost-effective approaches to further ex-
pand testing.
Of importance, realization of the prevention benefits of ex-
panded ART strategies depend on a number of components.
Retention in care and expanded financial, clinical, social, and
structural adherence and support measures for treatment, in-
cluding specific support for psychiatric and substance use co-
morbid conditions, and addressing homelessness and marginal
housing all need to be components of the strategy in a city such
as San Francisco. Also of concern is the potential for changes in
behavior among MSM leading to increased transmission risk,
thereby offsetting any potential gains and the specter of drug-
resistant strains of HIV. However, these obstacles are not in-
surmountable, as evidenced by the recent public health com-
mitment and movement to universal ART and a comprehensive,
multi-level HIV prevention strategy in San Francisco [16]. It is
possible that such strategies are comparatively cost-effective
and should be evaluated as data become available. Of note,
there is little observed evidence of significant increases in HIV
transmission risk behavior [9], and contrary to recent mod-
eling exercises, transmitted drug resistant HIV strains have
remained stable or even decreased in San Francisco and in
similar cities, such as Vancouver, where ART has rapidly ex-
panded [17–19].
Modeling of complex phenomena, such as a local HIV
epidemic and making cogent predictions about the future, are
subject to numerous limitations. In essence, modeling is
Table 1. Model Results
Prevalence of HIV infection,%
Baseline CD4 cell
count ,350 cells/mm
ART initiation, CD4
cell count ,500 cells/mm
Treat all in care
2009 24.7 24.7 24.7 24.7
2014 25.1 22.9 21.9 20.9
2019 25.5 21.7 19.4 17.5
2029 26.2 21.8 17.1 12.8
New HIV infections since 2009 Baseline (CD4,350) ART start CD4,500 Treat all in care Test-and-treat all
2014 3703 2149 1534 893
2019 7446 4344 2896 1406
2029 14,960 10,020 6739 2771
HIV Infections Averted* ART start CD4,500 Treat all in care Test-and-treat all
2014 Reference 1554 2169 2810
2019 Reference 3102 4550 6040
2029 Reference 4940 8221 12,189
Percent reduction in new HIV
Reference ART start CD4,500 Treat all in care Test-and-treat all
2014 Reference 42 59 76
2019 Reference 42 61 81
2029 Reference 33 55 81
HIV infections averted and percent reduction in new infections are relative to 2009 model estimates. Expansion of ART treatment strategies are assumed to
start in 2009.
CID 2011:52 (15 April)
Page 3
a thought experiment, informed by data, but subject to the
validity and completeness of the model’s internal structures.
The model presented here w hile able to recapitulate the
observed HIV epidemic in San Francisco from its beginning
with high fidelity does not sp ecifically mode l the impact
of acutely HIV-infected persons, which may be a sig-
nificant d river of new HIV infections or account for p ertur-
bations arising from HIV drug r esistance which may affect
virological suppre ssion rates; however, the sensitivity analyses
performed ind irectly address these issues by varying the reach
of HIV testing and ART effectiveness in producing viral
In conclusion, our projections suggest that ensuring HIV-
infected patients in San Francisco already receiving care are
offered ART would significantly reduce the incidence of HIV
infection in San Francisco. These predictions are supported by
recent surveillance data from San Francisco and Vancouver that
show decreasing rates of new HIV infections that correlate with
ART expansion and lower community viral load [20, 21]. With
new national and San Francisco Health Department ART
guidelines supporting treatment for most HIV-infected persons
for their individual health, secondary benefits of reducing HIV
transmission could be realized if adequate support for care de-
livery are in place.
The authors would like to acknowledge Drs Grant Colfax, Brad Hare,
Mitch Katz, Willi McFarland, and Susan Scheer for their assistance with
surveillance and clinic data and advice. This work was presented in part at
the 17th Conference on Retroviruses and Opportunistic Infections
(CROI), San Francisco, 2010, paper #996.
Financial Support. E.D.C. received support from NIH/NIMH center
grant P30MH062246 (Stephen F. Morin. PhD. PI).
Potential Conflicts of interest. D.V.H. has conducted two NIH-
funded stu dies in Uganda that were provided antiretrovi ral drugs by
Abbott. All other authors: no conflicts.
1. Granich RM, Gilks CF, Dye C, De Cock KM, Williams BG. Universal
voluntary HIV testing with immediate antiretroviral therapy as
a strategy for elimination of HIV transmission: a mathematical model.
Lancet 2009; 373:48–57.
2. Zetola NM, Bernstein K, Ahrens K, et al. Using surveillance data to
monitor entry into care of newly diagnosed HIV-infected persons: San
Francisco, 2006–2007. BMC Public Health 2009; 9:17.
3. HIV/AIDS Statistics and Epidemiology Section. HIV/AIDS Epidemi-
ology Annual Report 2008. San Francisco: San Francisco Department
of Public Health, 2009.
4. Blower SM, Gershengorn HB, Grant RM. A tale of two futures: HIV and
antiretroviral therapy in San Francisco. Science 2000; 287:650–4.
5. Dodd PJ, Garnett GP, Hallett TB. Examining the promise of HIV
elimination by ‘test and treat’ in hyperendemic settings. AIDS 2010;
6. HIV/AIDS Statistics and Epidemiology Section. HIV/AIDS Epidemi-
ology Annual Report 2008. San Francisco: San Francisco Department
of Public Health, 2009.
7. Schechter MT, Le N, Craib KJ, Le TN, O’Shaughnessy MV, Montaner JS.
Use of the Markov model to estimate the waiting times in a modified
WHO staging system for HIV infection. J Acquir Immune Defic Syndr
Hum Retrovirol 1995;8:4749.
8. Grant RM, Wiley JA, Winkelstein W. Infectivity of the human im-
munodeficiency virus: estimates from a prospective study of homo-
sexual men. J Infect Dis 1987; 156:189–93.
9. Donnell D, Baeten JM, Kiarie J, et al. Heterosexual HIV-1 transmission
after initiation of antiretroviral therapy: a prospective cohort analysis.
Lancet 2010; 375:2092–8.
10. El-Sadr WM, Mayer KH, Hodder SL. AIDS in America–forgotten but
not gone. N Engl J Med 2010; 362:967–70.
11. Scheer S, Chin CS, Buckman A, McFarland W. Estimation of HIV
incidence in San Francisco. AIDS 2009; 23:533–4.
12. Coates TJ, Richter L, Caceres C. Behavioural strategies to reduce HIV
transmission: how to make them work better. Lancet 2008 ;
13. Department of Health & Human Services (DHHS). Panel on anti-
retroviral guidelines for adults and adolescents. Guidelines for the use of
antiretroviral agents in HIV-1-infected adults and adolescents. Available
pdf. Accessed 2010:1–161.
14. Walensky RP, Paltiel AD, Losina E, et al. Test and Treat DC: Fore-
casting the Impact of a Comprehensive HIV Strategy in Washington
DC. Clin Infect Dis 2010; 51:392–400.
15. Charlebois ED, Havlir DV. ‘‘A bird in the hand’’: a commentary on the
test and treat approach for HIV. Arch Intern Med 2010; 170:1354–6.
16. Okie S. Fighting H.I.V., a community at a time. New York Times, 2009.
October 26 2009.
17. Blower S, Volberding P. What can modeling tell us a bout the threat
of antiviral drug resistance? Curr Opin Infect Dis 2002; 15:609–14.
18. Jain V, Pilcher C, Deeks S, et al. Increasing prevalence of NNRTI-
associated drug-resistance mutations in patients with acute, early HIV
in San Francisco. 16th Conference on Retroviruses and Opportunistic
infections. Boston: Massachusetts, 2009.
19. Gill VS, Lima VD, Zhang W, et al. Improved virological outcomes in
British Columbia concomitant with decreasing incidence of HIV type 1
drug resistance detection. Clin Infect Dis 2010; 50:98–105.
20. Das M, Chu PL, Santos GM, et al. Decreases in community viral load
are accompanied by reductions in new HIV infections in San Francisco.
PLoS One 2010; 5:e11068.
21. Montaner JS, Lima VD, Barrios R, et al. Association of highly active
antiretroviral therapy coverage, population viral load, and yearly new
HIV diagnoses in British Columbia, Canada: a population-based study.
Lancet 2010; 376:532–9.
CID 2011:52 (15 April)
Page 4
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    • "Although nearly two-thirds of our sample of newly HIV-infected MSM had been previously tested, no data were collected on last test or frequency of testing. It is therefore crucial for HIV prevention efforts to focus on strategies that increase testing coverage and identify the majority of HIV-infected persons [4] in order to link them to and retain them in care so that they may access preventive and life-prolonging antiretroviral treatment and ultimately reduce HIV transmission to others. Another concerning finding of this study is that those who were unaware of being HIV-infected were engaging in exceedingly high risk behaviors that could result in transmission to others. "
    [Show abstract] [Hide abstract] ABSTRACT: This study compared the correlates of HIV risk among men who have sex with men (MSM) with newly diagnosed versus previously known HIV infection among 5,148 MSM recruited using modified snowball sampling in 5 Peruvian cities. Participants, if age ≥18 years and reporting sex with a male in the previous 12 months, underwent standardized computer-assisted risk assessments and HIV and syphilis testing. Overall, 420 (8.2 %) participants tested HIV seropositive, most of whom (89.8 %) were unaware of their HIV status. Compared to those who knew themselves to be HIV-infected, multivariate logistic regression demonstrated that unprotected anal intercourse at last encounter [AOR = 2.84 (95 % CI 1.09-7.40)] and having an alcohol use disorder (AUD) [AOR = 2.14 (95 % CI 1.01-5.54)] were independently associated with a newly diagnosed HIV infection. Being unaware of being HIV-infected was associated with high-risk sexual behaviors and AUDs, both of which are amenable to behavioral and medication-assisted therapy interventions.
    Full-text · Article · May 2013 · AIDS and Behavior
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    • "To the Editor—Considerable momentum is gaining in support of increasing the coverage of antiretroviral treatment for human immunodeficiency virus (HIV)–infected people in order to prevent new infections. The potential population-level impact of antiretroviral therapy (ART) for prevention has been investigated with mathematical transmission models, including the study recently published in Clinical Infectious Diseases and authored by Charlebois et al that considered the potential impact of this strategy's implementation among men who have sex with men (MSM) in San Francisco [1]. As stated in the accompanying editorial, such thought experiments can serve a useful purpose in providing plausible ranges for the impact of the expansion of ART [2]. "
    Full-text · Article · Sep 2011 · Clinical Infectious Diseases
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    Preview · Article · Apr 2011 · Clinical Infectious Diseases
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