Weight Gain on Contemporary Integrase Strand Transfer Inhibitors and Tenofovir Alafenamide in Persons With HIV Starting Antiretroviral Therapy in the United States and Canada

Authors:

29 May 2026

journal article
Published by Oxford University Press (OUP) in The Journal of Infectious Diseases

Vol. 234 (3) , 352-360
DOI:10.1093/infdis/jiag271
PMID:42216675

Abstract

Background: Weight gain is common following antiretroviral therapy (ART) initiation. Integrase strand transfer inhibitors (INSTIs) and tenofovir alafenamide (TAF) have been associated with greater weight gain, though prior analyses may have been confounded by the weight-suppressive effects of efavirenz (EFV) and tenofovir disoproxil fumarate (TDF). Methods: Treatment-naive adults in the North American AIDS Cohort Collaboration on Research and Design initiating ART between 2007 and 2021 were analyzed. Predicted weight change was modeled using linear mixed effects models adjusted for demographic and clinical factors, and nucleoside reverse transcriptase inhibitor (NRTI) backbone, with subanalyses excluding EFV and stratifying by INSTI agent, NRTI, sex, and race. Results: A total of 32 514 persons were included. At 2 years, INSTIs (4.9 kg, 95% CI: 4.6–5.2) and protease inhibitors (PIs) (4.7 kg, 95% CI: 4.4–5.1) were associated with greater mean predicted weight gain compared to non-nucleoside reverse transcriptase inhibitors (NNRTIs) (2.7 kg, 95% CI: 2.4–2.9). Differences persisted when limiting analyses to TDF-containing regimens and excluding EFV. Among INSTIs, mean predicted weight gain was numerically highest with bictegravir (6.9 kg, 95% CI: 5.8–7.9), followed by dolutegravir (5.3 kg, 95% CI: 4.8–5.9), raltegravir (4.5 kg, 95% CI: 3.8–5.3), and elvitegravir (4.0 kg, 95% CI: 3.6–4.5). Participants receiving TAF with INSTIs gained more than those on TDF. Black females on bictegravir or dolutegravir with TAF had the highest gain at 2 years (10.0 kg, 95% CI: 7.4–12.6) Conclusions: Weight gain with non-EFV NNRTIs was lower than with PIs and INSTIs, with the greatest increases observed among Black females starting TAF with contemporary INSTIs.

Keywords

Funding Information

Gilead Sciences (GS-US-380-7018)
National Institutes of Health (U01AI069918)
National Institutes of Health (F31AI124794)
National Institutes of Health (F31DA037788)
National Institutes of Health (G12MD007583)
National Institutes of Health (K01AI093197)
National Institutes of Health (K01AI131895)
National Institutes of Health (K23EY013707)
National Institutes of Health (K24AI065298)
National Institutes of Health (K24AI118591)
National Institutes of Health (K24DA000432)
National Institutes of Health (KL2TR000421)
National Institutes of Health (N01CP01004)
National Institutes of Health (N02CP055504)
National Institutes of Health (N02CP91027)
National Institutes of Health (P30AI027757)
National Institutes of Health (P30AI027763)
National Institutes of Health (P30AI027767)
National Institutes of Health (P30AI036219)
National Institutes of Health (P30AI050409)
National Institutes of Health (P30AI050410)
National Institutes of Health (P30AI094189)
National Institutes of Health (P30AI110527)
National Institutes of Health (P30MH62246)
National Institutes of Health (R01AA016893)
National Institutes of Health (R01AG053100)
National Institutes of Health (R01AI177010)
National Institutes of Health (R01DA011602)
National Institutes of Health (R01DA012568)
National Institutes of Health (R24AI067039)
National Institutes of Health (R34DA045592)
National Institutes of Health (U01AA013566)
National Institutes of Health (U01AA020790)
National Institutes of Health (U01AI038855)
National Institutes of Health (U01AI038858)
National Institutes of Health (U01AI068634)
National Institutes of Health (U01AI068636)
National Institutes of Health (U01AI069432)
National Institutes of Health (U01AI069434)
National Institutes of Health (U01DA036297)
National Institutes of Health (U01DA036935)
National Institutes of Health (U10EY008057)
National Institutes of Health (U10EY008052)
National Institutes of Health (U10EY008067)
National Institutes of Health (U01HL146192)
National Institutes of Health (U01HL146193)
National Institutes of Health (U01HL146194)
National Institutes of Health (U01HL146201)
National Institutes of Health (U01HL146202)
National Institutes of Health (U01HL146203)
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National Institutes of Health (U01HL146205)
National Institutes of Health (U01HL146208)
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National Institutes of Health (U01HL146241)
National Institutes of Health (U01HL146242)
National Institutes of Health (U01HL146245)
National Institutes of Health (U01HL146333)
National Institutes of Health (U24AA020794)
National Institutes of Health (U54GM133807)
National Institutes of Health (UL1RR024131)
National Institutes of Health (UL1TR000004)
National Institutes of Health (UL1TR000083)
National Institutes of Health (UL1TR002378)
National Institutes of Health (Z01CP010214)
National Institutes of Health (Z01CP010176)
National Institute of Allergy and Infectious Diseases
Instituto Nacional do Câncer, Ministério da Saúde
National Heart, Lung, and Blood Institute
Eunice Kennedy Shriver National Institute of Child Health and Human Development
National Human Genome Research Institute
National Institute of Mental Health
National Institute on Drug Abuse
National Institute on Aging
National Institute of Dental and Craniofacial Research
National Institute of Neurological Disorders and Stroke
National Institute of Nursing Research
National Institute on Alcohol Abuse and Alcoholism
National Institute on Deafness and Other Communication Disorders
National Institute of Diabetes and Digestive and Kidney Diseases

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