women gain more weight than men following initiation of...
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Women Gain More Weight Than Men Following Initiation of Antiretroviral TherapySara H. Bares, Laura M. Smeaton, Ai Xu, Catherine Godfrey, and Grace A. McComsey
Study Rationale• Cross-sectional studies reveal a high prevalence of
obesity among HIV-infected individuals
• A number of studies have noted increases in weight gain after ART initiation with up to 20% of patients moving into a deleterious body mass index (BMI) category within 2 years of ART initiation in one study
• These short term gains in BMI have been directly linked to increases in the long term risk of both cardiovascular disease and diabetes mellitus
Crum-Cianflone N, et al. PLoS One 2010,5:e10106.Mulligan K, et al. Clin Infect Dis 2010,50:106-114.Taylor BS, et al. J Acquir Immune Defic Syndr 2014,65:e33-40.Tate T, et al. Antivir Ther 2012,17:1281-1289.Achhra AC, et al. HIV Med 2015.
BMI by year of HIV diagnosis
Crum-Cianflone N, et al. PLoS One 2010,5:e10106.
Are women living with HIV disproportionately affected? • Koethe and colleagues assessed temporal trends in
BMI among HIV-infected adults in NA-ACCORD and NHANES controls
– The BMI of NA-ACCORD participants caught up to the average BMI of matched NHANES controls after 3 years of ART
– Weight gain exceeded that of the general population in the case of HIV-infected females
Koethe J, et al. AIDS Research and Human Retroviruses 2016.
Prior studies with conflicting results• Observational cohort studies evaluating differences in
BMI increases following ART initiation in men and women have yielded conflicting results
• These studies have significant limitations: – Evaluated patients on a variety of ART regimens
that are no longer preferred– Not powered to look for sex differences in
changes in BMI
Amorosa V, et al. J Acquir Immune Defic Syndr 2005,39:557-561.Messina J, et al. J Assoc Nurses AIDS Care 2014,25:652-656.Hasse B, et al. J AIDS Clin Res 2014,5.Koethe JR, et al. AIDS Res Hum Retroviruses 2015.Lakey W, et al. AIDS Res Hum Retroviruses 2013,29:435-440.
Study Design• Three ACTG randomized trials (A5142 , A5202, and
A5257) assessed changes in BMI over 96 weeks in treatment-naïve individuals initiating ART with modern day regimens
• Opportunity to examine the relationship between sex and changes in BMI following ART initiation with scientific rigor
• A retrospective, cross-protocol, pooled analysis using data captured under ACTG protocols A5142, A5202, and A5257
Contributing Randomized Clinical TrialsStudy A5142 A5202 A5257
Enrollment and 96 week follow-up
Jan 2003 –Feb 2006
Sep 2005 –Sep 2009
May 2009 –June 2013
N 756 1857 1809
ART Regimens
EFV+NRTIs vs.
LPV/r+NRTIsvs.
EFV+LPV/r
EFV vs. ATV/r +
ABC/3TC vs. TDF/FTC
TDF/FTC + ATV/r vs.
TDF/FTC + DRV/rvs.
TDF/FTC + RAL
Riddler SA, et al. NEJM. 2008;358(20):2095-106.Daar ES, et al. Annals of internal medicine. 2011;154(7):445-56.Lennox JL, et al. Annals of internal medicine. 2014;161(7):461-71.
Study Objective• To evaluate whether BMI changes in the first 96
weeks following initiation of ART differ by sex
Between sex differences in the absolute and percent changes in BMI from baseline to week 96
Changes in the proportion of women in each of the BMI categories (obese/overweight/normal) after ART
Methods• Used multivariable linear regression to evaluate the
relationship between sex and change in BMI from baseline to 96 weeks
• Models were adjusted for the following demographic and clinical covariates assessed prior to ART initiation (baseline):
– Age – Race/ethnicity– CD4 cell count– HIV RNA level – Clinical trial and randomized ART regimen
Derivation of Analysis Sample• 4422 participants enrolled in the studies
• 3801 participants were included in the data analysis
• Participants excluded from this analysis if:
469 Left the study or died
71 Missed visit or missed BMI assessment
28 Pregnancy
22 Never started ART
20 Non-US enrollment
11 Sex at birth different from current gender
Baseline characteristics by inclusion in analysis
Included in analysis?No (n=621) Yes (n=3801) Total (n=4422) P-value
Age (years, mean) 36.0 38.3 38.0 <.001
BMI at baseline (kg/m2, mean) 25.6 25.9 25.8 0.2
Baseline CD4 (/mm3, mean) 247.1 261.0 259.1 0.08
Baseline HIV-1 RNA (log10 copies/mL, mean)
4.7 4.7 4.7 0.9
Sex
Female 149 (24%) 760 (20%) 909 (21%) 0.02
Race/ethnicity <0.001
White Non-Hispanic 189 (30%) 1,447 (38%) 1,636 (37%)
Black Non-Hispanic 294 (47%) 1,390 (37%) 1,684 (38%)
Hispanic 118 (19%) 849 (22%) 967 (22%)
Other/Unknown missing 20 (3%) 115 (3%) 135 (3%)
Baseline characteristics by sexWomen (n=760)
Men (n=3041) Total (n=3801) P-value
Age (years, mean) 40.5 37.7 38.3 <.001
BMI at baseline (kg/m2, mean)
28.4 25.2 25.9 <.001
Baseline CD4 (/mm3, mean) 260.2 261.2 261.0 0.887
Baseline HIV-1 RNA (log10 copies/mL, mean)
4.5 4.7 4.7 <.001
Race/ethnicity <0.001
White Non-Hispanic 127 (17%) 1,320 (43%)
1,447 (38%)
Black Non-Hispanic 439 (58%) 951 (31%) 1,390 (37%)
Hispanic 180 (24%) 669 (22%) 849 (22%)
Other/Unknown missing
14 (2%) 101 (3%) 115 (3%)
Observed mean change in BMI from baseline to week 96
Women(n=760)
Men(n=3041)
Sex difference p-value
Observed mean change in BMI from baseline to week 96
1.91 (1.64, 2.19)
1.39(1.30, 1.48)
0.52(0.29, 0.75)
<.001
Observed mean changes in BMI by baseline BMI category and sex
n (%) Women(n=760)
Men(n=3041)
Sex difference
p-value(t-test)
Underweight(< 18.5) 126 (3) 3.51 2.12 1.4 0.016
Normal(18.5 -< 25) 1802 (47) 2.37 1.68 0.69 0.003
Overweight(25-< 30) 1230 (32) 1.71 1.04 0.67 <0.001
Obese (≥ 30) 643 (17) 1.41 0.99 0.43 <0.001
BMI Category Change for Women
BMI category for women (with row %)
After 96 weeks follow-up (columns)
@ baseline (rows) Underweight Normal Overweight Obese
Underweight 9 (24%) 23 (62%) 5 (14%) 0 (0%)
Normal 4 (2%) 142 (58%) 81 (33%) 18 (7%)
Overweight 0 (0%) 31 (14%) 120 (54%) 72 (32%)
Obese 0 (0%) 2 (1%) 18 (7%) 235 (92%)
Change in BMI (kg/m2) from baseline to week 96 by sex
*Covariates: age, race/ethnicity, CD4 cell count, HIV RNA, contributing clinical trial and randomized ART regimen
Women(n=760)
Men(n=3041)
Sex difference p-value
Observed mean change in BMI from baseline to week 96
1.91 (1.64, 2.19)
1.39(1.30, 1.48)
0.52(0.29, 0.75)
<.001
Estimated mean change in BMI adjusting for covariates*
0.59(0.37, 0.81)
Sex differences (women - men) in BMI changes at week 96, based on CD4 cell count and HIV viral load
Subgroup Analysis• Performed on A5257 study in order to adjust for socio-
economic status (SES) as defined by highest education attained, alcohol and illicit drug use, smoking, and history of metabolic syndrome.
• Characteristics of subgroup analysis: - Comprised 43% of the overall BMI analysis- Overall sex difference in BMI change was 0.59
• Difference in BMI change by sex was not modified by SES, alcohol or illicit drug use, or metabolic syndrome.
• Interaction of smoking and sex was observed (estimated difference in mean BMI change over 96 weeks : women-men)
• Non-smokers (n= 711 , 43%) 0.86• Former smokers (n= 313 , 19%) 0.52• Current smokers (n= 616, 38%) - 0.04
Conclusions• In unadjusted analyses, women gained an average of
0.52 kg/m2 more BMI over the first 96 weeks on ART compared to men.
• After adjusting for important prognostic and potential confounders, women were estimated to gain an average of 0.59 kg/m2 more BMI over the first 96 weeks on ART compared to men.
Conclusions• Subgroup analysis suggests this excess weight gain in
women persists after additional adjustments for SES, substance and alcohol use, and identifies female non-smokers as a potential target group for a weight loss intervention.
• The fact that these sex differences in BMI change exist suggests an issue of real clinical significance for both providers and women living with HIV.
Next Steps• Evaluate whether changes in regional body
composition (central versus peripheral fat, lean mass) in the first 96 weeks of initiation of ART differ by sex.
• Estimate the association between selected markers of immune activation and inflammation before and after ART initiation with changes in body composition.
• Assess whether the relationship between immune activation/inflammation and body composition differs by sex.
Acknowledgements• Laura Smeaton and Ai Xu, Harvard TH Chan School of Public Health
• Catherine Godfrey, Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health
• Grace McComsey, Case Western Reserve University
• AIDS Clinical Trials Group
• Protocol team members for A5142, A5202, and A5257
• Study coordinators and participants at each of the study sites
• Work was supported by grants from the National Institutes of Health UM1AI068634 and UM1AI068636.