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.

Informations de copyright

Copyright © 2021 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests JMM received a personal 80:20 research grant from Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain, during 2017–21. JMM also reports grants and personal fees from AbbVie, Angelini, Contrafect, Cubist, Genentech, Gilead Sciences, Jansen, Lysovant, Medtronic, MSD, Novartis, Pfizer, and ViiV Healthcare, outside the submitted work. DLB reports honoraria from ViiV Healthcare, Gilead Sciences, and Merck, outside the submitted work. OK reports personal fees from Gilead Sciences, ViiV Healthcare, and Merck, outside the submitted work. ML reports grants from Gilead Sciences, Janssen-Cilag, and ViiV Healthcare, outside the submitted work. JH reports reimbursement to their institute from Gilead Sciences, ViiV Healthcare, and MSD, outside the submitted work. HFG reports grants from the Swiss National Science Foundation, National Institutes of Health (NIH), and the Swiss HIV Cohort Study, unrestricted research grants from Gilead Sciences, Roche, and Yvonne Jacob Foundation, personal fees from consulting or advisory boards or data safety monitoring boards for Merck, Gilead Sciences, ViiV Healthcare, Mepha, and Sandoz. HFG's institution received money for participation in the following clinical COVID-19 studies: 540-7773/5774 (Gilead), TICO (ACTIV-3, INSIGHT/NIH), and the Morningsky study (Roche). CSt reports personal fees and non-financial support from Gilead Sciences, ViiV Healthcare, and Janssen, outside the submitted work. VV is a salaried employee of ViiV Healthcare and receives GlaxoSmithKline stock. CD reports grants and personal fees from MSD, Gilead Sciences, and ViiV Healthcare, outside the submitted work. SDW reports grants from Gilead Sciences, MSD, Janssen, and ViiV Healthcare, outside the submitted work. FW reports membership of advisory boards for ViiV Healthcare and Gilead Sciences. JL reports personal fees from ViiV Healthcare, Gilead Sciences, and Janssen Cilag, outside the submitted work. CSm reports personal fees from Gilead Sciences, outside the submitted work. AdM reports grants from Gilead Sciences and ViiV Healthcare, during the conduct of the study, and personal fees from ViiV Healthcare, Gilead Sciences, Eiland, and Bonnin, outside the submitted work. NC reports personal fees from Virology Education, outside the submitted work. CO reports personal fees from ViiV Healthcare, Neola, and MSD, outside the submitted work. CO is also an elected member of the European AIDS Society governing body and of the EuroSIDA Steering Committee. JJV reports personal fees from MSD, Gilead Sciences, Pfizer, Astellas Pharma, Basilea, German Centre for Infection Research, University Hospital Freiburg, Congress and Communication, Academy for Infectious Medicine, University of Manchester, German Society for Infectious Diseases, Arztekammer Nordrhein, University Hospital Aachen, Back Bay Strategies, German Society for Internal Medicine, Shionogi, Molecular Health, Netzwerk Universitätsmedizin, Janssen, and NordForsk, and grants from MSD, Gilead Sciences, Pfizer, Astellas Pharma, Basilea, German Centre for Infection Research, German Federal Ministry of Education and Research, University of Bristol, and Rigshospitalet Copenhagen. JG is a paid employee of Gilead Sciences. ND reports he is a board member of non-governmental associations and initiatives (not for profit) that receive financial support from pharmaceutical companies and foundations for various projects. Those that have contributed are: GlaxoSmithKline, ViiV Healthcare, AbbVie, BMS, Gilead, Janssen-Cilag, MSD, AIDS Healthcare Foundation, Positive Action, Novartis, Roche, Mylam ELPEN, Cepheid, IPSEN, AstraZeneca, Amgen, Bayer, Pamaserve-Lilly, Roche Diagnostics, Sanofi, Pfizer, Theratechnologies, Vianex, Boehringer-Ingelheim, Chiesi, Takeda, and Leo Pharma. All other authors declare no competing interests.