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Lipodystrophy syndrome in HIV-infected patients – a cohort study in Lower Silesia, Poland

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Introduction: Human immunodeficiency virus (HIV)-associated lipodystrophy syndrome (LS) is defined as a redistribution of adipose tissue, metabolic and endocrine abnormalities, resulting from combined antiretroviral therapy (cART). Aim of this study was to evaluate LS in HIV-infected patients from Lower Silesia, Poland. Material and methods: One hundred and ten HIV-infected patients on cART for at leat 2 years were included. Two subgroups of patients were established: patients with no or slight symptoms of lipodystrophy – LS1; and patients with moderate and severe changes – LS2. The patients were also divided according to the type of LS: lipoatrophy, lipoaccumulation, both lipoatrophy and lipohypertrophy. Results: LS2 subgroup was significantly older, had much lower body weight, lower WHR, more advanced atherosclerotic changes. Patients with advanced lipodystrophy syndrome had very high pack-year values. LS1 group had hypertension much more frequently than controls. Comparing with controls, LS2 had significantly lower low-density lipoprotein (LDL) cholesterol, higher triglyceride levels, longer time of HIV infection, longer time of cART and cumulative time on cART (including PIs and NRTIs). A higher current CD4+ T-lymphocyte count and more frequent HCV infection in patients with more severe adipose tissue changes were of little statistical significance. Fat loss of face, limbs, buttocks and together with lipoaccumulation of abdomen were most common. Conclusions: Lipodystrophy syndrome is still observed in the vast majority of HIV-positive patients receiving antiretroviral therapy, especially those older and with longer time of cumulative NRTI and PI treatment. A great concern is needed to evaluate body composition and risk factors for metabolic changes to prevent their progression and healthy consequences.
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HIV & AIDS Review 2017/Volume 16/Number 1 HIV & AIDS Review 2017/Volume 16/Number 1
Lipodystrophy syndrome in HIV-infected
patients – a cohort study in Lower Silesia,
Poland
Justyna Drelichowska1,2, Wiesława Kwiatkowska1,2, Brygida Knysz1,3, Katarzyna Arczyńska1,
Marcin Czarnecki1,3, Jacek Gąsiorowski1,3, Maciej Karczewski1, Wojciech Witkiewicz1,2
1
Wrovasc – Integrated Cardiovascular Centre, Regional Specialist Hospital, Research and Development Center in Wroclaw,
Wroclaw, Poland
2
Department ofAngiology, Regional Specialist Hospital in Wroclaw, Research and Development Center in Wroclaw,
Wroclaw, Poland
3
Department ofInfectious Diseases, Wroclaw Medical University, Wroclaw, Poland
Abstract
Introduction: Human immunodeciency virus (HIV)-associated lipodystrophy syndrome (LS) is
dened as aredistribution ofadipose tissue, metabolic and endocrine abnormalities, resulting from
combined antiretroviral therapy (cART). Aim ofthis study was to evaluate LS in HIV-infected patients
from Lower Silesia, Poland.
Material and methods: One hundred and ten HIV-infected patients on cART for at leat 2 years were
included. Two subgroups ofpatients were established: patients with no or slight symptoms oflipodys-
trophy – LS1; and patients with moderate and severe changes – LS2. epatients were also divided
according to thetype ofLS: lipoatrophy, lipoaccumulation, both lipoatrophy and lipohypertrophy.
Results: LS2 subgroup was signicantly older, had much lower body weight, lower WHR, more ad-
vanced atherosclerotic changes. Patients with advanced lipodystrophy syndrome had very high pack-
year values. LS1 group had hypertension much more frequently than controls. Comparing with con-
trols, LS2 had signicantly lower low-density lipoprotein (LDL) cholesterol, higher triglyceride levels,
longer time ofHIV infection, longer time ofcART and cumulative time on cART (including PIs and
NRTIs). A higher current CD4+ T-lymphocyte count and more frequent HCV infection in patients
with more severe adipose tissue changes were oflittle statistical signicance. Fat loss offace, limbs,
buttocks and together with lipoaccumulation ofabdomen were most common.
Conclusions: Lipodystrophy syndrome is still observed in thevast majority ofHIV-positive patients
receiving antiretroviral therapy, especially those older and with longer time ofcumulative NRTI and
PI treatment. A great concern is needed to evaluate body composition and risk factors formetabolic
changes to prevent their progression and healthy consequences.
HIV AIDS Rev 2017; 16: 40-49
DOI: https://doi.org/10.5114/hivar.2017.65114
Key words: HIV, antiretroviral therapy, lipodystrophy syndrome, metabolic abnormalities.
Address for correspondence: Brygida Knysz,
Department of Infectious Diseases, Wroclaw Medical University,
5 Koszarowa St., 51-149 Wroclaw, Poland,
e-mail: brygida.knysz@gmail.com
Article history
Received: 11.07.2016
Received in revised form: 20.10.2016
Accepted: 31.10.2016
Available online: 20.01.2017
RESEARCH PAPER
Lipodystrophy syndrome in HIV-infected patients 41
HIV & AIDS Review 2017/Volume 16/Number 1
Table 1. Virological and immunological characteristics ofpatients on antiretroviral therapy
Infection data Results
Mode oftransmission HET/IDU/MSM, n [%] 31/51/28 (28.2/46.4/25.5)
Time ofHIV infection [years]* 8 (3.4-12.0)
AIDS, n [%] 32 (29.1)
HCV infection, n [%] 59 (53.6)
HBV infection, n [%] 26 (23.6)
CD4+ T-lymphocytes [cells/μl]* 515 (388-693)
CD4+ T-lymphocyte nadir [cells/μl]* 200 (66-280)
Log10 HIV RNA at themoment oftest [copies/ml]* 1.7 (1.6-1.7)
HIV RNA below thesensitivity ofthemethod, n [%] 93 (84.5%)
Log10 HIV RNA zenith, copies/ml, n =84* 4.7 (3.6-5.3)
cART Results
Time ofARV treatment [years]* 4 (2-8)
Cumulative time on PI [years]* 3.79 (0.71-7.37)
Cumulative time on NNRTI [years]* 0 (0-1.6)
Cumulative time on NRTI [years]* 8.79 (4.03-13.98)
Cumulative time on cART [years]* 16.6 (8.13-24.97)
*Median, IQR, n (%) – absolute number (percentage), other data – arithmetic mean
HET – heterosexual contacts, IDU – intravenous drug users, MSM – men who have sex with men
Introduction
Human immunodeciency virus (HIV)-associated lipo-
dystrophy syndrome (LS) is dened as aredistribution ofad-
ipose tissue accompanied by metabolic and endocrine ab-
normalities, resulting from combined antiretroviral therapy
(cART) [1-5].
e term was rst used in 1998 by Andrew Carr et al.
to describe morphological and metabolic abnormalities
observed in HIV-infected patients treated with protease in-
hibitors (PIs) [2]. However, further studies also discovered
the inuence of other antiretroviral drugs, mostly nucleo-
side reverse transcriptase inhibitors (NRTIs), and of HIV
infection itself [6-11]. Most authors emphasize thesigni-
cant role ofadipose tissue in pathogenesis ofthis condition;
therole ofthe immune system, proinammatory cytokines
such as TNF-α and interleukin (IL)-6 and genetic predispo-
sition are also mentioned [2, 3, 8, 12, 13].
e morphological abnormalities observed in clinical
presentation of patients with LS include: lipoatrophy (loss
of subcutaneous adipose tissue in the face, limbs, and but-
tocks), isolated or accompanied by lipoaccumulation (growth
of adipose tissue in the abdomen, waist, neck and growth
ofvisceral adipose tissue) [14-19].
Lipoatrophy should be distinguished from cachexia
and malnutrition observed in advanced stages ofAIDS and
chronic infections accompanying HIV infection. erapy
with PI is considered by many authors as an independent risk
factor for the development of insulin resistance, abnormal
glucose tolerance and diabetes mellitus type 2 [20-24]. Other
metabolic abnormalities include: increased triglyceride concen-
tration, low-density lipoprotein (LDL) and very-low-density
lipoprotein (VLDL) cholesterol and apolipoproteins B and E
levels, lower high-density lipoprotein (HDL) cholesterol level
[25-27].
e aim ofthis study was to evaluate thelipodystrophy
syndrome in HIV-infected patients living in Lower Silesia,
Poland.
Material and methods
Material
One hundred and ten HIV-infected patients, treated
in the Acquired Immunodeciency Syndrome Outpatient
Clinic in Wroclaw were included in theobservational study.
e same study population was analyzed in our previous
publications [28]. epreliminary inclusion criteria were:
documented HIV infection and antiretroviral therapy, of no
less than 2 years. eexclusion criteria were: AIDS diag-
nosis, acute medical condition (fever, severe infection, in-
ammation), serum creatinine level over 2 mg% and over
vefold increase in the alanine aminotransferase level, body
mass index (BMI) > 30 kg/m2, age over 65 years old, diabe-
tes, treatment with such drugs as metphormin. efollow-
ing patient data were known at thebeginning ofthestudy:
current virological and immune status, history of the in-
fection and information about coinfection with hepatitis B
and/or hepatitis C virus (Table 1).
All patients were on antiretroviral treatment for 2-8
years, 4 years on average. etime ofcumulative antiretrovi-
ral treatment with medications from all antiretroviral classes
Justyna Drelichowska, Wiesława Kwiatkowska, Brygida Knysz et al.42
HIV & AIDS Review 2017/Volume 16/Number 1
was from about 8 to 25 years, 16.6 years on average; thelon-
gest cumulative time oftreatment concerned NRTI. We did
not analyze contribution ofcertain antiretroviral drugs and
their classes in the LS. Before the beginning of this study
there were changes in thecART in many patients because
ofdrug toxicity and viral failure.
e control group included 42 healthy individuals living
in Lower Silesia, matched for age and sex with thepatients,
with negative medical history ofchronic diseases and car-
diovascular disease events (Table 2).
Characteristics ofthe study group (SG) and control group
(CG) are presented in Table 2.
Methods
e study protocol included collecting anamnesis and
data from medical documentation, especially information
about HIV infection and antiretroviral treatment (in years
and cumulative treatment with NNRTI, NRTI, PI). Physical
examination was performed with particular emphasis on an-
thropometric measurements – weight, height, waist and hip
circumferences, BMI and waist-hip ratio (WHR). eevalu-
ation ofclinical features ofLS was carried out using theme-
thodology of HIV Outpatient Study (HOPS), a multi-site
clinical study of over 4800 patients receiving ambulatory
care in theUSA in 1992-1998 [18].
Table 2. Characteristics of the study group (SG) and control group (CG)
Feature SG, n = 110 CG, n = 42 p-value
Age [years] (a, sd) 39.8 ± 9.3 (20-62) 41 ± 11.5 (20-58) 0.48
Sex (male), n [%] 70 (63.6) 26 (61.9) 0.99
BMI* 22.86 (21-25) 25.6 (24-27) 0.0001
Waist [cm]* 82.75 (76.5-91.0) 86.75 (75-95)
Hips [cm]* 94 (88-98) 100 (95-105)
WHR* 0.9 (0.84-0.96) 0.89 (0.78-0.94) 0.055
Smokers, n [%] 46 (84.6) 28 (47.6) 0.0001
Pack-years* 18 (8.875-27.125) 13.375 (4-27.5) 0.33
cIMT [mm]* 0.66 (0.58-0.78) 0.54 (0.46-0.62) 0.0001
cIMT mean-max [mm]* 0.99 (0.84-1.18) 0.81 (0.67-0.99) 0.0001
Atherosclerotic plaques, n [%] 35 (31.8) 7 (16.7) 0.12
Hypertension, n [%] 49 (44.5) 10 (23.8) 0.039
TC [mg/dl] (a,sd) 195.3 ± 45.4 212.67 ± 38.7 0.03
Non-HDL [mg/dl] 139.2 ± 42.4 150.41 ± 35.7 0.13
LDL [mg/dl] (a,sd) 110.13 ± 38.1 126.34 ± 31.7 0.016
HDL [mg/dl]* 51 (40-64) 58.5 (47-71) 0.012
TG [mg/dl]* 131.5 (93-189) 100.5 (68-137) 0.0077
Fasting glucose [mg%]* 91 (86.0-96.5) 93.5 (87-101) 0.11
Insulin [UI/ml]* 7.15 (5.2-10.4) 7 (4.4-10.9) 0.64
HOMA-IR*,** 1.63 (1.1-2.23) 1.48 (0.98-2.67) 0.9
Insulin resistance, n [%] 21 (19.4) 11 (27.5) 0.55
CRP [mg/l]* 0.62 (0.19-1.53) 0.72 (0.19-1.52) 0.89
Fibrinogen [g/l]* 2.7 (2.3-3.2) 2.9 (2.6-3.3) 0.037
D-dimers [ng/ml]* 216.6 (169-319) 245.7 (170-349) 0.78
Positive family history, n [%] 35 (31.8) 5 (11.9) 0.022
Metabolic syndrome, n [%] 22 (20) 5 (11.9) 0.35
Diabetes, n [%] 3 (2.7) 0 (0) 0.66
Obesity/overweight/underweight, n [%] 6/21/7 (5.5/19.1/6.3) 5/23/0 (12/54.8/0) 0.0001
Cardiovascular disease risk factors, n [%] 3 (2.7)
CV – ATP III risk*,*** 2 (1-6) 2 (1-5) 0.38
*Median, IQR, n (%) – absolute number (percentage), other data – arithmetic mean
**Homeostatic Model Assessment of Insulin Resistance
***Cardio-vascular risk according Adult Treatment Panel III
Lipodystrophy syndrome in HIV-infected patients 43
HIV & AIDS Review 2017/Volume 16/Number 1
eLS features were evaluated by two physicians – re-
searchers, taking into consideration patients’ opinions.
e physical examination included evaluation of upper
and lower limbs, buttocks, hips and face regarding fat loss
and ofvisceral regions, trunk and neck with regard to fat
accumulation. eresearchers graded all thechanges from
0 points (absent) to 3 points (the most severe). emaxi-
mum possible score was 15 points.
equantitative parameter for lipodystrophy was used
for analyzing dependencies between lipodystrophy and
atherosclerosis. All changes were classied in afour-degree
scale reecting theseverity oflipodystrophy syndrome: no
LS symptoms, subtle changes – noticeable only if specically
looked for, with no change in clothing t (up to 3 points),
moderate changes – easily noted by the patient or physician,
oen requiring achange in clothing size (3-7 points), severe
changes obvious to thecasual observer, requiring achange
in clothing size (over 7 points) (Figure 1).
Following the HOPS method, two main subgroups
ofpatients were established:
1) patients with no or slight symptoms oflipodystrophy
(57 individuals) – LS1,
2) patients with moderate and severe changes (53 indi-
viduals) – LS2.
e purpose of this division was to compare their vi-
rological, immunological and clinical state and to evaluate
thedata concerning cART in both subgroups. epatients
were also divided according to thetype of lipodystrophic
changes, into thefollowing subgroups: lipoatrophy (n = 34),
lipoaccumulation (n = 14), mixed forms – features ofboth
lipoatrophic and lipohypertrophic changes (n = 46). In
thecontrol group, no features oflipoatrophic or mixed lipo-
dystrophic changes were observed; 15 controls had symp-
toms ofvisceral obesity.
In all patients, aduplex ultrasound ofcarotid was per-
formed in order to evaluate subclinical atherosclerosis
by means of computer-measured cIMT. Carotid ultra-
sound was performed using a high-resolution ultrasound
GE LOGIQ 7 GE with broadband linear probe 6-12 MHz.
emain parameters for each patient were cIMT (the aver-
age IMT value obtained for all theseries) and IMT mean-
max (dened as theaverage of12 maximal IMT measure-
ments from each projection) [29].
Statistical analysis
Quantitative variables were presented as an arithmetic
mean, geometric mean or median, depending on normal-
ity of distribution. To achieve normality, the logarithmic
transform was applied to thevariable elements. For each
estimator, 95% condence intervals were calculated. Qual-
itative variables are presented as thenumber ofpatients in
each group. Dierences in quantitative features between
groups were analyzed by Student’s t-test, the Mann-Whit-
ney test or Kruskal-Wallis wit post-hoc analysis. Dierences
in thequalitative features were analyzed using theχ2 test or
Fisher’s exact test (for small groups). e eect of clinical
features on lipodystrophy was assessed using logistic regres-
sion. eanalysis was made using R and MedCalc statistical
packages. All results with asignicance level p < 0.05 were
found signicant.
e study was conducted with theapproval oftheBio-
ethics Committee. All participants provided their written
informed consent to participate in thestudy, according to
theHelsinki Declaration.
Results
At thebeginning ofthestudy, thepatients were classied
according to theseverity of lipodystrophy syndrome, from
no LS symptoms to severe changes in adipose tissue distri-
bution. e subgroups with subtle and moderate changes
were themost numerous (Figure 1).
Table 3 presents and compares thecharacteristics ofboth
subgroups. e patients from LS2 subgroup were signi-
cantly older, had much lower body weight and smaller hip
circumference and, as aresult, lower WHR.
Patients from LS2 subgroup had noticeably more ad-
vanced atherosclerotic changes, expressed by higher cIMT
values. Both LS1 and LS2 patients had signicantly high-
er IMT mean-max values in comparison with thecontrol
group. Among traditional risk factors, there was anotice-
able dierence concerning smoking. Patients with advanced
lipo dystrophy syndrome had very high pack-year values.
Aer further post-hoc analysis ofsubgroups and the control
group, it was discovered that LS1 had hypertension much
more frequently than controls (0.033). In comparison with
the control group, LS2 had signicantly lower LDL choles-
terol and higher triglyceride values (p = 0.015, p = 0.028
respectively). No other statistically signicant dierences in
basic laboratory parameters or concerning cardiovascular
disease risk factors were observed (Table 3).
Patients in LS2 subgroup had noticeably longer doc-
umented time ofHIV infection (Table 4). General time
ofcART and cumulative time on antiretroviral drugs, in-
cluding cumulative time on PIs and cumulative time on
Figure 1. Classification of patients according to the severity
of lipodystrophy syndrome
45
40
35
30
25
20
15
10
5
0
Number ofpatients
Severity oflipodystrophy syndrome
1 2 3 4
Justyna Drelichowska, Wiesława Kwiatkowska, Brygida Knysz et al.44
HIV & AIDS Review 2017/Volume 16/Number 1
NRTIs, were significantly longer in LS2. Some interesting
findings oflittle statistical significance indicate ahigher
current CD4+ T-lymphocyte count and more frequent
HCV infection in patients with more severe adipose tissue
changes.
Various combinations of fat distribution abnormalities
were observed in LS patients. emost common one was
cumulative fat loss in areas ofthe face, limbs, waist and hips
(lipo atrophy); another frequent pattern was lipoatrophy
combined with lipoaccumulation in the visceral area (mixed
lipodystrophy). epercentages ofparticular combinations
are presented in Figure 2.
Within thewhole group, all types ofdystrophic chang-
es were observed: lipoatrophy (30.9%), lipoaccumulation
(12.7%) and, most frequently, mixed forms (41.7%). Figure 3
shows numbers ofpatients in specic subgroups, according
to various dystrophic changes.
Table 5 presents statistically signicant dierences ob-
served in patients with dierent types of lipodystrophy.
ere were signicant dierences between thesubgroups,
concerning anthropometric measurements: BMI and waist
circumference were noticeably higher in lipoaccumula-
tion and mixed subgroups than in the lipoatrophy group;
hip circumference was signicantly lower in the atrophy
Table 3. Clinical and laboratory characteristics of patients from subgroups LS1 and LS2
Feature LS1, n = 57 LS2, n = 53 p-value
Age [years] (a,sd) 39 (31.75-43) 42 (35-48) 0.048
Sex (male), n [%] 33 (57.9) 37 (69.8) 0.38
BMI* 23.9 (21.6-25.7) 22 (20.6-24.0) 0.015
Waist [cm]* 81 (75.6-90.0) 84 (79.0-91.5) 0.29
Hips [cm]* 95 (90-100) 90.5 (87-95) 0.014
WHR* 0.88 (0.80-0.94) 0.93 (0.88-1.00) 0.0024
cIMT [mm]* 0.64 (0.56-0.76) 0.71 (0.61-0.82) 0.026
cIMT mean-max [mm]* 0.93 (0.83-1.12) 1.06 (0.90-1.21) 0.076
Atherosclerotic plaques, n [%] 15 (26.3) 20 (37.7) 0.28
Smokers, n [%] 45 (79.0) 48 (90.6) 0.18
Pack-years* 12 (5.75-21.50) 23.375 (13.3-29.5) 0.0017
Hypertension, n [%] 28 (50.9) 20 (37.7) 0.23
TC [mg/dl] (a, sd) 204 (164-226) 187 (156-223) 0.82
Non HDL-C [mg/dl] 143 (105-168.75) 128 (100.75-166) 0.71
LDL-C [mg/dl] (a, sd) 114 (82.75-145.75) 101.8 (80.00-124.5) 0.36
HDL-C [mg/dl]* 53 (40-62) 49 (40.5-68.0) 0.75
TG [mg/dl]* 131 (95.25-183.25) 132 (91.50-196.75) 0.75
Fasting glucose [mg%]* 91 (86.00-97.53) 91 (85.75-96.00) 0.71
Insulin [IU/ml]* 6.7 (5.45-8.93) 7.8 (4.80-11.43) 0.15
HOMA-IR*,** 1.46 (1.14-1.91) 1.91 (1.08-2.59) 0.13
Insulin resistance, n [%] 7 (12.7) 14 (26.4) 0.18
CRP [mg/l]* 0.47 (0.18-1.40) 0.89 (0.2-2) 0.13
Fibrinogen [g/l]* 2.61 (2.3-3.1) 2.71 (2.28-3.40) 0.47
D-dimers [ng/ml]* 201.8 (169.0-316.0) 253.2 (171.9-331.0) 0.18
Positive family history, n [%] 18 (31.6) 17 (32.1) 0.89
Metabolic syndrome, n [%] 12 (21.1) 10 (18.9) 0.96
Diabetes, n [%] 1 (1.8) 2 (3.8) 0.94
Obesity/overweight/underweight, n [%] 5/11/5 (8.8/19.3/8.8) 1/10/4 (1.9/18.9/7.5) 0.43
Cardiovascular disease risk factors, n [%] 0 (0) 3 (5.7) 0.23
CV – ATP III risk*, *** 2 (1-6) 2 (1-8) 0.45
*Median, IQR, n (%) – absolute number (percentage), other data – arithmetic mean
**Homeostatic Model Assessment of Insulin Resistance
***Cardio-vascular risk according Adult Treatment Panel III
Lipodystrophy syndrome in HIV-infected patients 45
HIV & AIDS Review 2017/Volume 16/Number 1
group, compared with accumulation and mixed subgroups;
it was thehighest in the accumulation subgroup in com-
parison to mixed and no-LS groups. WHR was noticeably
higher in the mixed subgroup than in no-LS and atrophy
groups. Patients with mixed changes were signicantly old-
er and had more advanced atherosclerotic changes (cIMT
mean-max), compared with no-LS group. cIMT values and
pack-years were oflittle statistical signicance. Metabolic
syndrome was observed among thepatients with adipose
tissue accumulation and with mixed forms. esubgroups
ofpatients with various dystrophic changes did not dier
in: occurrence of atherosclerotic plaques, results oflabo-
Table 4. Infection characteristics in subgroups LS1 and LS2
Infection data LS1 LS2 p-value
Mode of transmission HET/IDU/MSM**, n [%] 16/24/17
(28.1/42.1/29.8)
15/27/11
(28.3/50.9/20.8) 0.51
Time of HIV infection [years]* 4.5 (2.5-9.0) 11 (5.75-17.00) 0.0003
AIDS, n [%] 15 (26.3) 17 (32.1) 0.65
HCV infection, n [%] 25 (43.9) 34 (64.2) 0.071
HBV infection, n [%] 11 (19.3) 15 (28.3) 0.37
CD4+ T-lymphocytes [cells/µl]* 488 (386.5-632.25) 609 (400.75-760.25) 0.053
CD4+ T-lymphocyte nadir [cells/µl]* 200 (49.00-267.75) 198 (77.25-293.00) 0.68
Log10 HIV RNA at the moment of test [copies/ml]* 1.69 (1.6-1.7) 1.6 (1.6-1.7) 0.28
HIV RNA below the sensitivity of the method, n [%] 45 (78.9) 48 (90.6) 0.21
Log10 HIV RNA zenith, copies/ml* (n = 84) 4.27 (3.31-5.13) 4.93 (4.06-5.38) 0.14
cART LS1 LS2 p-value
Time of cART [years]* 3 (1-7) 6 (3-10) 0.0007
Cumulative time on PI [years]* 2.25 (0.10-5.67) 5.27 (2.14-8.44) 0.01
Cumulative time on NNRTI [years]* 0 (0-1.3) 0 (0-2.65) 0.42
Cumulative time on NRTI [years]* 6.22 (2.3-11.7) 10.59 (6.00-14.50) 0.0049
Cumulative time on cART [years]* 12.43 (4.7-21.2) 19.92 (12.40-28.00) 0.0021
*Median, IQR, n (%) – absolute number (percentage), other data – arithmetic mean
HET – heterosexual contacts, IDU – intravenous drug users, MSM – men who have sex with men
Figure 3. Numbers of patients with various dystrophic changes
50
45
40
35
30
25
20
15
10
5
0
Number ofpatients
Type oflipodystrophy syndrome
No LD Atrophy Accumulation Mixed
Lipoatrophy ofthe face, limbs and buttocks
Lipoatrophy ofthe face, limbs and buttocks + lipoaccumulation ofabdomen
Lipoaccumulation ofabdomen
Lipoatrophy ofthe face and limbs
Lipoatrophy ofthe face and lipoaccumulation ofabdomen
Lipoatrophy ofthe face, limbs and buttocks + lipoaccumulation ofabdomen
and neck
Lipoaccumulation ofabdomen and neck
Lipoatrophy ofthe face and limbs + lipoaccumulation ofabdomen and neck
Lipoatrophy ofthe face and limbs + lipoaccumulation ofabdomen
Lipoatrophy ofthe face
Other combinations
Figure 2. Combinations of dystrophic changes in lipodystrophy
syndrome patients
23%
21%
11%
7%
5%
5%
4%
3%
3%
3% 16%
Justyna Drelichowska, Wiesława Kwiatkowska, Brygida Knysz et al.46
HIV & AIDS Review 2017/Volume 16/Number 1
ratory tests (lipid prole, glucose, insulin, CRP, brinogen,
D-dimers), and in such risk factors as: cardiovascular dis-
ease risk factors, hypertension, diabetes or positive family
hi s tory.
e time ofHIV infection, cumulative time ofNRTIs and
cumulative time on cART were signicantly longer in the
mixed subgroup than in no-LS group (Table 5). No signi-
cant dierences were discovered in the mode ofHIV trans-
mission and immunological or virological state. e time
ofantiretroviral treatment and total time ofPIs and NNRTIs
treatment were similar.
In further analysis of logistic regression cumulative
cART and smoking had an inuence on theseverity oflipo-
dystrophy syndrome (Table 6). In subsequent models, aer
disregarding cumulative cART and including cumulative
NRTIs and PIs treatment, and then NNRTIs treatment, it was
discovered that cumulative NRTIs treatment and smoking
had an independent inuence on severity oflipodystrophy
syndrome (p = 0.004 and p = 0.0152, respectively) (Table 6).
Adding the current number of CD4+ T-lymphocytes to
themodel did not change theresult and had no impact on
theseverity ofLS.
Discussion
Prevalence of LS in HIV-infected patients varies from
8% to 84% in dierent studies; it is usually correlated to
thecharacteristics ofthe research project, inclusion criteria
and observation time [1, 10, 18, 19, 22, 30-32].
In this study, 94 out of110 patients were diagnosed with
LS, which represents 85% ofthe study group. is is not an
isolated case ofsuch a high percentage ofLS diagnosis. Sim-
ilar results were observed by Rozenbaum et al. (84%) and by
Carr et al. (83%) [14, 19].
However, some studies indicate amuch lower prevalence
ofLS, e.g. Martinez et al. diagnosed it in 17% of patients,
Mercie et al. – in 26% ofpatients [25, 27].
All types of dystrophic changes were observed in our
study, with themajority ofmixed forms (41.7%), lipoatro-
phy (30.9%) and, least frequently, lipoaccumulation (12.7%).
ese results are consistent with the ndings of the HIV
Outpatient Study, where LS was diagnosed in 49% of pa-
tients, mixed forms were most frequent (22.7%) and preva-
lence oflipoatrophy (13.3%) and lipoaccumulation (13.2%)
were similar [18]. Dierent ndings were presented by ie-
baut et al. in aFrench cohort, where mixed forms were least
Table 5. Statistically significant differences in subgroups depending on LS type
Feature
(0)
No LS
n=16
(1)
Atrophy
n=34
(2)
Accumulation
n=14
(3)
Mixed
n=46
p-value Post hoc
Age
(years) (a,sd) 33 (26.5-42.0) 40 (31.0-48.0) 33.5 (32.0-41.0) 41.5 (38.0-47.0) 0.015 0 vs. 3, p = 0.052
BMI* 23.6 (20.9-25) 21.1 (19.4-23.0) 25.4 (24.2-28.1) 23.4 (21.6-25.3) 0.0001 1 vs. 2, p = 0.0001
1 vs. 3, p = 0.006
Waist (cm)* 78 (73.5-85.5) 78.5 (74.0-86.0) 86 (81.0-101.0) 85 (80.5-95.0) 0.0001
0 vs. 3, p = 0.023
1 vs. 3, p = 0.003
1 vs. 2, p = 0.042
Hips (cm)* 94.5 (88.5-1.0) 90 (84.0-94.0) 100.5 (98.0-103.0) 94 (88.0-98.0) 0.0001
1 vs. 2, p = 0.0001
2 vs. 3, p = 0.003
1 vs. 3, p = 0.056
0 vs. 2, p = 0.054
WHR* 0.846 (0.79-0.91) 0.882 (0.84-0.94) 0.886 (0.8-0.93) 0.944 (0.88-1.01) 0.001 0 vs. 3, p = 0.002
1 vs. 3, p = 0.033
Smokers, n (%) 15 (93.7) 32 (94.1) 12 (85.7) 34 (73.9) 0.06
cIMT (mm)* 0.613 (0.54-0.75) 0.657 (0.57-0.81) 0.631 (0.54-0.82) 0.7 (0.61-0.81) 0.099
cIMT mean-
max (mm)* 0.859 (0.75-1.8) 0.96 (0.84-1.26) 0.968 (0.83-1.26) 1.062 (0.91-1.19) 0.039 0 vs. 3, p = 0.029
Metabolic
syndrome, n (%) 2 (12.5) 0 (0) 5 (35.7) 15 (32.6) 0.001 1 vs. 2, p = 0.002
1 vs. 3, p = 0.002
Time of HIV
infection, years* 4 (2.050-8.0) 7 (3.0-12.0) 3 (1.0-9.0) 11 (5.0-17.0) 0.006 0 vs. 3, p = 0.027
Cumulative
NRTI (years)* 2.49 (0.2-12.40) 8.54 (4.9-12.7) 4.41 (3.2-10.7) 11.04 (5.7-14.2) 0.03 0 vs. 3, p = 0.05
Cumulative
cART (years)* 6.75 (2.3-21.3) 17.15 (9.6-21.9) 9.28 (6.4-22.5) 20.2 (11.2-27.9) 0.045 0 vs. 3, p = 0.073
*Median, IQR, n (%) – absolute number (percentage), other data – arithmetic mean, post-hoc analysis
Lipodystrophy syndrome in HIV-infected patients 47
HIV & AIDS Review 2017/Volume 16/Number 1
frequent (10%), lipoatrophy was most common (16%) and
isolated lipoaccumulation was observed in 12% out of38%
ofpatients diagnosed with LS [26].
Trevisol et al. observed high frequencies of lipoaccu-
mulation (46%) and lipoatrophy (53.2%) in agroup where
53.2% ofHIV-infected patients were diagnosed with LS [33].
In the presented cohort, signicant dierences in an-
thropometric measurements were observed, depending on
the type and severity of LS. Patients with more advanced
LS had lower BMI and higher WHR. ehigher WHR was
aconsequence ofa signicantly lower hip circumference, re-
sulting from adipose tissue loss in this region.
A higher BMI and waist circumference was observed
in patients with lipoaccumulation and with mixed forms.
Patients with lipoatrophy had a noticeably lower hip cir-
cumference. Patients with mixed forms had signicantly
higher WHR in comparison to no-LS and atrophy sub-
groups. e relation between dystrophic changes and an-
thropometric measurements was studied by iebaut et al.
Among patients receiving cART, theprevalence oflipoatrophy
grew with age and was higher in males and in patients with
BMI ≤ 25. Lipoaccumulation was correlated to higher BMI and
WHR; no signicant relationship between lipoaccumulation
and age has been discovered. epercentage ofmixed forms
was correlated to older age and higher WHR [26]. However,
Alencastro et al. observed a dierent correlation between dys-
trophic changes and age or BMI. In their research, patients on
antiretroviral therapy were older and had signicantly higher
BMI. Lipodystrophy and lipohypertrophy were correlated to
age and BMI, whereas lipoatrophy was only correlated to BMI,
without any signicant inuence ofage [6]. Mercie et al. ob-
served signicantly older age ofpatients diagnosed with LS and
noticeably lower BMI and CD4+ T-lymphocyte count in com-
parison with cART-using patients with no LS [25]. In thema-
jority ofndings, LS features are found in patients treated
with antiretroviral therapy [6, 7].
One ofthemain inclusion criteria for thepresent study
was antiretroviral treatment. Its signicant inuence was ob-
served especially in thesubgroup ofpatients with severe LS.
einuence ofboth total and cumulative time ofcART on
LS types and severity has been discovered. Cumulative pro-
tease inhibitors treatment was related to LS severity, but not
to LS types. NRTIs medications were correlated to LS devel-
opment. Cumulative time ofNRTIs treatment had inuence
on severity oflipodystrophy and occurrence ofmixed forms.
e inuence of time of cART on LS and its relationship
with various types oflipodystrophy have been observed in
numerous clinical studies [1, 7, 11, 18, 26, 27].
However, iebaut et al. did not observe asignicant re-
lationship between LS and particular antiretroviral medica-
tions, except for theinuence oftime on cART on LS types
and severity ofsymptoms [26].
In many clinical studies, theinuence ofvarious classes
of antiretroviral drugs and of specic antiretroviral drugs
on LS in HIV-infected patients was observed. Since thein-
troduction ofantiretroviral treatment, PIs has been therst
class whose side eects have been described as lipodystro-
phy syndrome. einuence of this class of medications,
specic drugs and time ofPI treatment on LS development
and severity have been widely described [1, 2, 6, 11, 14, 27].
In one ofthe rst LS studies in 1999, Carr et al., aer
an over twenty-month long observation, discovered fat dis-
tribution disorders in PI-treated patients in comparison to
HIV-infected, untreated patients [14]. PIs were closely as-
sociated with visceral adipose tissue growth and adverse
changes in patients’ metabolic prole. Since LS was also
observed in patients never treated with PIs, further studies
proved the negative inuence of other classes of antiret-
Table 6. Influence of various factors on severity of lipodystrophy
Variable OR 95% CI pVariable OR 95% CI p
MODEL 1 MODEL 2
Age 1.0479 0.9912-1.1078 0.099 Age 1.0518 0.9936-1.1134 0.08
Sex 1.4816 0.5399-4.0658 0.45 Sex 1.6447 0.5851-4.6234 0.35
Pack-years 1.0245 0.9908-1.0594 0.16 Pack-years 1.0247 0.9910-1.0595 0.15
Hypertension 2.0866 0.7542-5.7732 0.16 Hypertension 1.9614 0.7019-5.4810 0.2
HOMA-IR* 1.4392 0.9025-2.2952 0.13 HOMA-IR* 1.3715 0.8629-2.1799 0.18
HCV 0.4784 0.1806-1.2678 0.14 HCV 0.4993 0.1868-1.3344 0.17
Cumulative cART 1.0571 1.0128-1.1033 0.011 Cumulative NRTI 1.0856 1.0027-1.1754 0.0428
Cumulative PI 1.094 0.9653-1.2398 0.16
Stepwise
Variable OR 95% CI pVariable OR 95% CI p
Pack-years 1.0373 1.0066-1.0689 0.0168 Pack-years 1.0377 1.0072-1.0693 0.0152
Cumulative cART 1.0628 1.0198-1.1076 0.0039 Cumulative NRTI 1.1148 1.0353-1.2003 0.004
Logistic regression
*Homeostatic Model Assessment of Insulin Resistance
Justyna Drelichowska, Wiesława Kwiatkowska, Brygida Knysz et al.48
HIV & AIDS Review 2017/Volume 16/Number 1
roviral drugs on LS development [7, 8, 11, 31]. Peripheral
lipo atrophy is mostly associated with some NRTIs [5, 8,
11, 34]. Mallal et al. also found independent inuence of
NRTIs on LS; moreover, they discovered acorrelation be-
tween thetime ofNRTIs treatment, theuse oftwo dierent
medications ofthis class and theincreased risk oflipoatro-
phy. In their study of an Australian cohort ofHIV-infect-
ed patients, evident inuence ofPIs on faster development
ofNRTI-induced atrophic changes, even in comparison to
treatment with two dierent NRTI drugs, without PI, was
observed. ey discovered a slow development oflipoatro-
phy in NRTI-treated patients and progression of atrophic
changes when combination therapy ofNRTIs and PIs was
used [11]. einuence ofcART on LS prevalence was also
studied by van der Valk et al. In their research, LS was more
frequently diagnosed in patients on PIs and NRTIs treat-
ment than in patients on PIs treatment alone [7]. In thepres-
ent study, more severe LS and mixed forms were observed in
patients with a signicantly longer documented time ofHIV
infection. ese patients were also older. ese observations
are consistent with most publications. ecorrelation be-
tween the time of HIV infection, its severity, patients’ age
and prevalence and severity ofdystrophic changes is undis-
putable [6, 18, 27]. Mercie et al. discovered avisibly lower
CD4+ T-lymphocyte count in agroup ofsignicantly old-
er patients with LS than in ano-LS group [25]. In thestudy
of1240 patients, Alencastro et al. observed acorrelation be-
tween LS and cART treatment with longer time since HIV
diagnosis, older age and CD4+ T-lymphocyte count below
350 cells/µl [6]. But we did not nd any signicant correla-
tion between CD4 Tcell count (nadir and present) and LS
severity, probably because ofthe low number of patients.
e lipid prole ofthe study group diered signicantly
from theprole ofthe control group. In thestudy group, total
cholesterol, LDL and HDL levels were signicantly lower, and
triglyceride concentration was signicantly higher. In compar-
ison with the control group, the LDL cholesterol level was no-
ticeably lower and TG concentration was signicantly higher
in patients with severe lipodystrophy (LS2). evast majority
ofauthors describing lipid dysfunction in HIV-infected patients
also observe hypertriglyceridemia [1, 25, 26, 30, 35-37]. Mercie
et al. also discovered asignicantly higher TG concentration in
LS patients than in no-LS subgroup [25]. Moreover, Hsue et al.
observed arelationship between ahigh TG concentration and
PI treatment [38]. Another metabolic dysfunction frequently
observed in HIV-infected patients is ahigher total cholesterol
level, contrary to thendings ofthis study [25, 26, 30].
Mercie et al. conrmed therelation between ahigh TC
level and LS diagnosis [25]. Hsue et al. did not observe sig-
nicant dierences in TC levels between HIV-patients and
healthy controls. ey have, however, discovered a notice-
ably lower HDL level in comparison to the control group,
which was also observed in other studies and in theresearch
presented here [25, 38]. Mercie et al. demonstrated high to-
tal cholesterol and LDL levels, apart from thelow HDL level,
which is interpreted as arisk factor for atherosclerosis and
cardiovascular diseases, especially in patients with LS [25].
Conclusions
Lipodystrophy syndrome is still observed in thevast ma-
jority ofHIV-positive patients receiving antiretroviral ther-
apy, especially those older and with longer time ofcumula-
tive NRTI and PI treatment. Smoking is an independent risk
factor of the severity of adipose tissue redistribution. Agreat
concern is needed to evaluate body composition and risk
factors formetabolic changes to prevent their progression
and healthy consequences.
Acknowledgment
is publication is a part oftheProject “Wrovasc – Inte-
grated Cardiovascular Centre, co-nanced by the European
Regional Development Fund, within Innovative Economy Op-
erational Program, 2007-2013, realized in the Regional Special-
ist Hospital, Research and Development Center in Wroclaw.
Conict of interest
e author’s declared no potential conicts ofinterest
with respect to theresearch, authorship, and/or publication
ofthis article.
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... One very positive aspect is the subjects' avoidance or very rare consumption of fast food. In view of the generally high proportion of fats in the diet and the risk of lipid disorders in people with HIV, 21,22 it is a good sign that the respondents are limiting highly-processed fast foods. Considering the current recommendations in terms of fish consumption for healthy people, 20,33 it is worth focusing on problem of how rarely of these products are consumed. ...
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Background: The aim of this study was to determine the consumption of specific food groups by people with HIV and to determine the quality of their diets. Objectives: To assess the relationship between selected eating habits and lifestyles of people infected with HIV. The research was conducted at the HIV/AIDS Preventative and Therapeutic Clinic of the Infectious Disease Prevention and Therapy Center at Wrocław Health Center (SPZOZ Wrocław), Poland. Material and methods: The study was conducted in 2019 among 31 patients of a counselling center in Wrocław. To determine the frequency of food consumption and eating habits, the KomPAN® questionnaire, prepared by employees of the Polish Academy of Sciences, was used. Results: All study participants were characterized by a small degree of unhealthy features in their diets; 87% of the respondents also demonstrated a small degree of healthy features in their diets, although the responses they gave showed that they assessed their nutritional knowledge and diet highly. Consumption of sweet snacks and adding salt to cooked meals were prevalent. The respondents took part in moderate physical activity and rarely consumed highly processed fast food products, though they ate fish and legumes - an important part of the diet - with similar frequency. Conclusions: More attention should be given to the nutritional issues of patients treated for HIV, and emphasis should be placed on promoting healthy eating habits among this population. In the scientific literature, few such studies are available that address issues related to the diet of HIV-infected people.
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Background: Cardio-metabolic risk factors are of increasing concern in HIV-infected individuals, particularly with the advent of antiretroviral therapy (ART) and the subsequent rise in longevity. However, the prevalence of cardio-metabolic abnormalities in this population and the differential contribution, if any, of HIV specific factors to their distribution, are poorly understood. Therefore, we conducted a systematic review and meta-analysis to estimate the global prevalence of metabolic syndrome (MS) in HIV-infected populations, its variation by the different diagnostic criteria, severity of HIV infection, ART used and other major predictive characteristics. Methods: We performed a comprehensive search on major databases for original research articles published between 1998 and 2015. The pooled overall prevalence as well as by specific groups and subgroups were computed using random effects models. Results: A total of 65 studies across five continents comprising 55094 HIV-infected participants aged 17-73 years (median age 41 years) were included in the final meta-analysis. The overall prevalence of MS according to the following criteria were: ATPIII-2001:16.7% (95%CI: 14.6-18.8), IDF-2005: 18% (95%CI: 14.0-22.4), ATPIII-2004-2005: 24.6% (95%CI: 20.6-28.8), Modified ATPIII-2005: 27.9% (95%CI: 6.7-56.5), JIS-2009: 29.6% (95%CI: 22.9-36.8), and EGIR: 31.3% (95%CI: 26.8-36.0). By some MS criteria, the prevalence was significantly higher in women than in men (IDF-2005: 23.2% vs. 13.4, p = 0.030), in ART compared to non-ART users (ATPIII-2001: 18.4% vs. 11.8%, p = 0.001), and varied significantly by participant age, duration of HIV diagnosis, severity of infection, non-nucleoside reverse transcriptase inhibitors (NNRTIs) use and date of study publication. Across criteria, there were significant differences in MS prevalence by sub-groups such as in men, the Americas, older publications, regional studies, younger adults, smokers, ART-naïve participants, NNRTIs users, participants with shorter duration of diagnosed infection and across the spectrum of HIV severity. Substantial heterogeneities across and within criteria were not fully explained by major study characteristics, while evidence of publication bias was marginal. Conclusions: The similar range of MS prevalence in the HIV-infected and general populations highlights the common drivers of this condition. Thus, cardio-metabolic assessments need to be routinely included in the holistic management of the HIV-infected individual. Management strategies recommended for MS in the general population will likely provide similar benefits in the HIV-infected.
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The highly active antiretroviral therapy (HAART) has altered the course of HIV infection, transforming it from a fatal illness to a chronic condition, reducing morbidity and mortality. However, this therapy has led to an increased incidence of metabolic problems such as insulin resistance, dyslipidemia, lipodystrophy and impaired glucose metabolism. The objectives of this study are to determine the prevalence of insulin resistance (IR) in a cohort of human immunodeficiency virus (HIV)-infected patients on highly active antiretroviral therapy (HAART) and to investigate the potentially associated factors. We conducted a cross-sectional study including 219 adult patients with HIV on HAART. IR was determined through the homeostasis model assessment (HOMA-IR) mathematical model, using fasting plasma glucose (FPG) and insulin. Bivariate and multivariate analyses were performed to assess the association between demographic information, clinical characteristics and laboratory results, and IR. 75 (34.2 %) [95 % confidence interval (CI) 28.9-40.9] HIV-patients on HAART showed IR. 61 (81 %) of these patients were on HAART for more than one year, which was mainly composed by non-protease inhibitors drugs (88 %). Metabolic syndrome (MS) was found in 59 (26.9 %) subjects. In the multivariate analysis, the factors associated with IR were age ≥ 46 years (Prevalence ratio = 2.767, 95 % CI 1.325 to 5.780) and greater body mass index (BMI) (Prevalence ratio = 1.148, 95 % CI 1.054 to 1.250). The prevalence of IR was 34.2 %. Factors associated with IR were age and BMI. We did not find any significant association between IR and protease inhibitors (PI), which may be explained by the small number of patients using PI as part of their HAART regimen included in our study.
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Peripheral arterial disease (PAD) is a clinical manifestation of atherosclerosis and mainly refers to elderly patients, having a negative impact on their functionality and quality of life. The findings of previous studies in HIV-infected patients have shown that cardiovascular risk is higher and PAD occurs more frequently than in the general population. There are also contradictory observations. Much less is known about the ankle-brachial index (ABI) value in asymptomatic HIV-infected patients. The aim of this study was to evaluate the prevalence of PAD and ankle-brachial index abnormalities as well as to determine risk factors related to the disease in a group of Polish HIV-positive patients. One hundred and eleven young to middle aged HIV-positive subjects and 40 noninfected subjects were enrolled into the study. Resting ABI measurements were performed and cardiovascular risk was analysed as well. Subgroups were created according to the ABI values: low (PAD), borderline, normal, high and altered ABI. Symptomatic PAD was observed in 2 HIV-positive patients, asymptomatic PAD was not diagnosed. The ABI value is lower and more varied, in 22.5% of the study group altered ABI values were found. Six subjects demonstrated borderline ABI, and 15 high ABI, including >1.4. In the control group no low or very high values were reported. A relation between low ABI and cardiovascular family history and between altered ABI and high-density-lipoprotein cholesterol (HDL-C) level was demonstrated. In young and middle-aged HIV-positive patients, symptomatic PAD prevalence is comparable to that observed in the overall population. Among asymptomatic patients PAD is not reported. The ABI value in HIV-positive patients is more varied compared to the HIV-negative subjects; the altered ABI shows a strong relation with low HDL-C levels and metabolic syndrome.
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Abstract We report a case of a 17-year-old girl with a history of congenital human immunodeficiency virus (HIV) infection and lipodystrophy secondary to highly active antiretroviral therapy (HAART). She developed severe worsening of preexisting hypertriglyceridemia after treatment with oral contraceptive pills (OCP) for polycystic ovary syndrome. Her hypertriglyceridemia improved upon OCP discontinuation. Although it is known that estrogen combined with progestins have a negative effect on triglycerides and high-density lipoprotein (HDL) cholesterol levels, to our knowledge the association of HAART-related lipodystrophy and severe hypertriglyceridemia after OCP use has not been reported in the literature. We recommend avoiding the use of OCPs in patients with lipodystrophy due to the increased risk of worsening hypertriglyceridemia.
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Background: Metabolic syndrome (MetS) is considered an independent risk factor for developing cardiovascular disease. It is well known that the prevalence of metabolic disorders have increased in pediatric HIV-infected children. The objective of this study is to assess the prevalence and characteristics of MetS in HIV-infected children and adolescents in Spain. Methods: A cross-sectional multicenter study in 152 patients from the pediatric cohort of the Spanish AIDS Research Network (CoRISpe) was performed. MetS was defined according to the new International Diabetes Federation (IDF) diagnostic criteria and the modified National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) criteria. Measurements included anthropometry, waist circumference, blood pressure, fasting lipids, glucose and insulin and lipodystrophy assessment. Demographic, clinical, immunological, virological and antiretroviral therapy data were obtained from the Network database. Results: An abnormally low high-density lipoprotein-cholesterol level was the most prevalent disturbance (21.05%) found. Three patients met IDF criteria for MetS (1.97%), and MetS was significantly associated with lipohypertrophy (P=0.029) in the analysis. When the modified NCEP-ATP III criteria were used, the prevalence of MetS was 5.92% (9 patients), and MetS was significantly associated with Tanner stage ≥2 (P=0.041), lipohypertrophy (P=0.001) and higher Z scores for weight and body mass index (P=0.002 and P<0.001). Insulin resistance was observed in 17 patients (11.18%) and was associated with MetS (as per the modified NCEP-ATP III criteria) (P=0.03) and lower high-density lipoprotein-cholesterol values (P=0.036). Conclusions: The prevalence of MetS in our cohort was 1.97% or 5.92%, depending on the diagnostic criteria used. MetS should be actively assessed, particularly in children who show lipohypertrophy.
Article
Background: The use of combination antiretroviral therapy (cART) has significantly decreased the morbidity and mortality associated with human immunodeficiency virus (HIV) infection. Lipid disorders, including lipodystrophy, hypertriglyceridemia, and hypercholesterolemia, remain the most commonly reported metabolic disorders among those treated with long-term cART. Mounting evidence suggests an association between drug abuse and poor glycemic control and diabetes complications. Substance related disorders (SRD) may increase the risk of metabolic syndrome. Materials and methods: The aim of this retrospective cohort study was to examine the relationship between SRD, cART, and lipid-lowering agent use in an HIV infected population. Patients received efavirenz or protease inhibitor-based cART for at least 6 months. Prescription information was retrieved from the medical records. The primary outcome was the use of lipid-lowering agents including statins, fibrates and fish oil. The impact of SRD and cART was assessed on the lipid-lowering agent use. Results: A total of 276 subjects with HIV infection were included, 90 (33%) received lipid-lowering agents, and 31 (34%) had SRD. Smoking was prevalent among subjects with SRD (84 vs 15%, p<0.001). Statins were the mainstay for the management of dyslipidemia (66%), followed by the fibrates (24%), omega-3 fatty acids (5%), nicotinic acid (3%) and the cholesterol absorption inhibitors (3%). Use of statins or fibrates was significantly higher among subjects without SRD than those with (40 vs 23%, p=0.005). The type of cART, including efavirenz and protease inhibitors, appeared to have no significant impact on the use pattern of lipid-lowering agents. Lopinavir/ritonavir (lopinavir/r) was mostly prescribed for subjects with SRD (25 vs 8%, p=0.02). Conclusion: Among HIV-infected patients, statins remain the mainstay for the management of dyslipidemia in routine clinical care, followed by fibrates. A significant high risk of metabolic disorders among patients with SRD is implicated by heavy tobacco use and prevalent lopinavir/r-based treatment. Significantly low rate of lipid-lowering agent use in this population underscores the importance of lipid disorder scrutiny and cART treatment optimization for HIV-infected patients with SRD.
Article
Context: Lipodystrophy (LD) is a relatively rare complex collection of diseases that can be congenital or acquired. It is commonly missed in the clinical setting. Thus, the spectrum of disease presentation mandates clinician expertise in the pathophysiology and management of all forms of LD, obesity, and insulin resistance. Methods and materials: An extensive literature search of clinical trials, systematic reviews, and narrative reviews was completed in PubMed for the years 1970 to 2013. The search terms were lipodystrophy, congenital LD, acquired LD, HIV-associated LD, severe insulin resistance, adiposity, obesity, and dyslipidemia. Evidence synthesis: Lipodystrophies are a heterogeneous group of disorders with abnormal adipose tissue distribution, utilization, and metabolism. Adipose tissue can undergo significant changes in composition (hypertrophy and atrophy) in response to a nutritional state. Paradoxically, both excess and deficient adipose tissue is associated with insulin resistance and the metabolic syndrome. Bone density scan (DEXA) for body fat composition analysis or magnetic resonance imaging are optimal modalities for the assessment of abnormal adipose tissue distribution. Ongoing clinical studies suggest thiazolidinediones, insulin like growth factor-1, leptin, and growth hormone-releasing hormone as possible treatment for LPD; however, none of them is approved to reverse fat loss or treat severe insulin resistance due to LPD. Conclusion: The underlying mechanisms for LPD causing insulin resistance may be lipotoxicity and derangements in adipose tissue-derived proteins (adipocytokines). However, the lack of evidence to support this model means that clinicians are on their own as they navigate through the phenotypic presentation of lipodystrophies, obesity, insulin resistance, and the metabolic syndrome.
Article
HIV-associated lipodystrophy is a heterogeneous, evolving condition associated with fundamental defects in adipose tissue differentiation, turnover and function. Although many antiretroviral drugs can affect adipose tissues adversely, clinical evidence suggests that factors associated with the virus per se could play a role. We have focused on the possibility that an HIV accessory protein, viral protein R (Vpr) could dysregulate metabolically critical transcription factors to cause the adipose dysfunction. In a recent study published in Science Translational Medicine, we utilized 2 animal models to show that Vpr, produced in tissues that sequester HIV after antiretroviral therapy, can act in a paracrine or endocrine fashion to disrupt adipocyte differentiation and function by inhibiting PPARγ target gene expression and activating glucocorticoid target gene expression. The phenotypic consequences included many features typical of the human syndrome, including accelerated lipolysis, increased macrophage infiltration in adipose tissue, diminished size of white adipose depots and hepatic steatosis. In this commentary, we summarize the background, results, and implications of these studies, and raise important questions for future investigation. More broadly, these studies suggest that chronic viral infections may be a causative factor in the pathogenesis of some forms of lipid metabolic disease, insulin resistance, and diabetes.
Article
Objective: Body image disturbance is a common experience for sexual minority men living with HIV, and is associated with poor self-care behaviors. However, to date, no known cohesive theoretical model has been advanced to understand the possible antecedents and outcomes of body image disturbance in this population. Thus, the goal of the current study was to test a biopsychosocial model of body image and self-care behaviors among sexual minority men living with HIV. Method: Participants were 106 gay and bisexual men living with HIV who completed a battery of self-report measures, including assessment of body image disturbance, depression, lipodystrophy, appearance orientation, condom use self-efficacy, antiretroviral therapy (ART) adherence, and HIV sexual transmission risk behaviors. Bayesian estimation was employed to assess model fit and direct and indirect pathways within the model. Results: The data fit the model well, with all theorized pathways being significant. Lipodystrophy severity and appearance orientation were associated with elevated body image disturbance. In turn, body image disturbance was related to poorer ART adherence and increased HIV sexual transmission risk behaviors, through the mechanisms of elevated depressive symptoms and poor condom use self-efficacy. Conclusions: Elevated body image disturbance among sexual minority men living with HIV is associated with important biopsychosocial variables, which in turn are related to poorer ART adherence and increased HIV sexual transmission risk behaviors. Integrative psychosocial interventions addressing co-occurring body image disturbance, depression, and HIV self-care behaviors may be a fruitful area for future clinical practice and research.