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

Kassem Bourgi; Aihua Bian; Lakeisha Boyd; Samir K Gupta; Cal Cohen; Jean C Lee; Timothy R Sterling; Richard D Moore; Catherine Lesko; Jordan E Lake; George A Yendewa; Michael A Horberg; Michael J Silverberg; Frank J Palella Jr; Keri Althoff; Joseph Margolick; Peter R Rebeiro; John R Koethe

doi:10.1093/infdis/jiag271

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

J Infect Dis. 2026 May 29:jiag271. doi: 10.1093/infdis/jiag271. Online ahead of print.

Authors

Kassem Bourgi^{1

2

3}, Aihua Bian³, Lakeisha Boyd², Samir K Gupta², Cal Cohen⁴, Jean C Lee⁴, Timothy R Sterling³, Richard D Moore⁵, Catherine Lesko⁶, Jordan E Lake⁷, George A Yendewa⁸, Michael A Horberg⁹, Michael J Silverberg¹⁰, Frank J Palella Jr¹¹, Keri Althoff⁶, Joseph Margolick⁶, Peter R Rebeiro³, John R Koethe³

Affiliations

¹ Nashville CARES, Nashville, TN, USA.
² Indiana University School of Medicine, Indianapolis, IN, USA.
³ Vanderbilt University Medical Center, Nashville, TN, USA.
⁴ Gilead Sciences, Foster City, CA, USA.
⁵ Johns Hopkins School of Medicine, Baltimore, MD, USA.
⁶ Johns Hopkins School of Public Health; Baltimore, MD, USA.
⁷ UTHealth, Houston, TX, USA.
⁸ Case Western Reserve University School of Medicine, Cleveland, OH, USA.
⁹ Mid-Atlantic Permanente Research Institute, Kaiser Permanente Mid-Atlantic Permanente Medical Group, Washington, District of Columbia, USA.
¹⁰ Kaiser Permanente Northern California, Oakland, CA, USA.
¹¹ Northwestern University, Chicago, IL, USA.

PMID: 42216675
DOI: 10.1093/infdis/jiag271

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-naïve adults in the North American AIDS Cohort Collaboration on Research and Design initiating ART between 2007-2020 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 sub-analyses excluding EFV and stratifying by INSTI agent, NRTI, sex, and race.

Results: 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: Antiretroviral Therapy; HIV; Integrase Inhibitors; Tenofovir Alafenamide; Weight Gain.

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