Weight Gain and Metabolic Effects in Persons With HIV Who Switch to ART Regimens Containing Integrase Inhibitors or Tenofovir Alafenamide

Frank J. Palella, MD; Qingjiang Hou, MS; Jun Li, MD; Jonathan Mahnken, PhD; Kimberly J. Carlson, MPH; Marcus Durham, MS; Douglas Ward, MD; Jack Fuhrer, MD; Ellen Tedaldi, MD; Richard Novak, MD; Kate Buchacz, PhD


J Acquir Immune Defic Syndr. 2023;92(1):67-75. 

In This Article

Abstract and Introduction


Background: The timing and magnitude of antiretroviral therapy–associated weight change attributions are unclear.

Setting: HIV Outpatient Study participants.

Methods: We analyzed 2007–2018 records of virally suppressed (VS) persons without integrase inhibitor (INSTI) experience who switched to either INSTI-based or another non–INSTI-based ART, and remained VS. We analyzed BMI changes using linear mixed models, INSTI- and tenofovir alafenamide (TAF) contributions to BMI change by linear mixed models–estimated slopes, and BMI inflection points.

Results: Among 736 participants (5316 person-years), 441 (60%) switched to INSTI-based ART; the remainder to non–INSTI-based ART. The mean follow-up was 7.15 years for INSTI recipients and 7.35 years for non-INSTI. Preswitch, INSTI and non-INSTI groups had similar median BMI (26.3 versus 25.9 kg/m2, P = 0.41). INSTI regimens included raltegravir (178), elvitegravir (112), and dolutegravir (143). Monthly BMI increases postswitch were greater with INSTI than non-INSTI (0.0525 versus 0.006, P < 0.001). A BMI inflection point occurred 8 months after switch among INSTI users; slopes were similar regardless of TAF use immediately postswitch. Among INSTI + TAF users, during 8 months postswitch, 87% of BMI slope change was associated with INSTI use, 13% with TAF use; after 8 months, estimated contributions were 27% and 73%, respectively. For non-INSTI+TAF, 84% of BMI gain was TAF-associated consistently postswitch. Persons switching from TDF to TAF had greater BMI increases than others (P < 0.001).

Conclusion: Among VS persons who switched ART, INSTI and TAF use were independently associated with BMI increases. During 8 months postswitch, BMI changes were greatest and most associated with INSTI use; afterward, gradual BMI gain was largely TAF-associated.


The precise magnitude, timing, and persistence of antiretroviral therapy (ART)–associated weight gain observed with use of integrase strand transfer inhibitors (INSTIs) and/or tenofovir alafenamide (TAF) remain unclear. Similarly unclear is whether such weight gain is associated with adverse metabolic changes and if, among virally suppressed people with HIV (PWH) switching ART, it matters whether the prior regimen included drugs that could potentially exert a suppressive effect upon weight gain[1–3] including efavirenz or tenofovir disoproxil fumarate (TDF).[1–3] In the current report, we studied diverse virally suppressed INSTI-naïve PWH who switched to ART that did or did not include INSTIs and/or TAF.