Hiv/Aids

Contemporary antiretrovirals and body-mass index: a prospective study of the RESPOND cohort consortium

Background

Weight gain effects of individual antiretroviral drugs are not fully understood. We
investigated associations between a prespecified clinically significant increase (>7%)
in body-mass index (BMI) and contemporary antiretroviral use.

Methods

The International Cohort Consortium of Infectious Diseases (RESPOND) is a prospective,
multicohort collaboration, including data from 17 well established cohorts and over
29 000 people living with HIV. People with HIV under prospective follow-up from Jan
1, 2012, and older than 18 years were eligible for inclusion. Each cohort contributed
a predefined minimum number of participants related to the size of the specific cohort
(with a minimum of 1000 participants). Participants were required to have CD4 cell
counts and HIV viral load measurement in the 12 months before or within 3 months after
baseline. For all antiretroviral drugs received at or after RESPOND entry, changes
from pre-antiretroviral BMI levels (baseline) were considered at each BMI measurement
during antiretroviral treatment. We used logistic regression to identify individual
antiretrovirals that were associated with first occurrence of a more than 7% increase
in BMI from pre-antiretroviral BMI. We adjusted analyses for time on antiretrovirals,
pre-antiretroviral BMI, demographics, geographical region, CD4 cell count, viral load,
smoking status, and AIDS at baseline.

Results

14 703 people were included in this study, of whom 7863 (53·5%) had a more than 7%
increase in BMI. Compared with lamivudine, use of dolutegravir (odds ratio [OR] 1·27,
95% CI 1·17–1·38), raltegravir (1·37, 1·20–1·56), and tenofovir alafenamide (1·38,
1·22–1·35) was significantly associated with a more than 7% BMI increase, as was low
pre-antiretroviral BMI (2·10, 1·91–2·31 for underweight vs healthy weight) and Black ethnicity (1·61, 1·47–1·76 vs White ethnicity). Higher CD4 count was associated with a reduced risk of BMI increase
(0·97, 0·96–0·98 per 100 cells per μL increase). Relative to lamivudine, dolutegravir
without tenofovir alafenamide (OR 1·21, 95% CI 1·19–1·32) and tenofovir alafenamide
without dolutegravir (1·33, 1·15–1·53) remained independently associated with a more
than 7% increase in BMI; the associations were higher when dolutegravir and tenofovir
alafenamide were used concomitantly (1·79, 1·52–2·11, and 1·70, 1·44–2·01, respectively).

Interpretation

Clinicians and people with HIV should be aware of associations between weight gain
and use of dolutegravir, tenofovir alafenamide, and raltegravir, particularly given
the potential consequences of weight gain, such as insulin resistance, dyslipidaemia,
and hypertension.

Funding

The CHU St Pierre Brussels HIV Cohort, The Austrian HIV Cohort Study, The Australian
HIV Observational Database, The AIDS Therapy Evaluation in the Netherlands national
observational HIV cohort, The EuroSIDA cohort, The Frankfurt HIV Cohort Study, The
Georgian National AIDS Health Information System, The Nice HIV Cohort, The ICONA Foundation,
The Modena HIV Cohort, The PISCIS Cohort Study, The Swiss HIV Cohort Study, The Swedish
InfCare HIV Cohort, The Royal Free HIV Cohort Study, The San Raffaele Scientific Institute,
The University Hospital Bonn HIV Cohort and The University of Cologne HIV Cohorts,
ViiV Healthcare, and Gilead Sciences.


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