Brief Report: Weight Gain Following ART Initiation in ART-Naïve People Living With HIV in the Current Treatment Era

Abstract

Objectives: Evaluate differences in weight change by regimen among people living with HIV (PLWH) initiating antiretroviral therapy (ART) in the current era. Methods: Between 2012 and 2019, 3232 ART-naïve PLWH initiated ≥3-drug ART regimens in 8 Centers for AIDS Research Network of Integrated Clinical Systems sites. We estimated weight change by regimen for 11 regimens in the immediate (first 6 months) and extended (all follow-up on initial regimen) periods using linear mixed models adjusted for time on regimen, interaction between time and regimen, age, sex, race/ethnicity, hepatitis B/C coinfection, nadir CD4, smoking, diabetes, antipsychotic medication, and site. We included more recently approved regimens [eg, with tenofovir alafenamide fumarate (TAF)] only in the immediate period analyses to ensure comparable follow-up time. Results: Mean follow-up was 1.9 years on initial ART regimen. In comparison to efavirenz/tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC), initiating bictegravir/TAF/FTC {3.9 kg [95% confidence interval (CI): 2.2 to 5.5]} and dolutegravir/TAF/FTC [4.4 kg (95% CI: 2.1 to 6.6)] were associated with the greatest weight gain in the immediate period, followed by darunavir/TDF/FTC [3.7 kg (95% CI: 2.1 to 5.2)] and dolutegravir/TDF/FTC [2.6 kg (95% CI: 1.3 to 3.9)]. In the extended period, compared with efavirenz/TDF/FTC, initiating darunavir/TDF/FTC was associated with a 1.0 kg (95% CI: 0.5 to 1.5) per 6-months greater weight gain, whereas dolutegravir/abacavir/FTC was associated with a 0.6-kg (95% CI: 0.3 to 0.9) and dolutegravir/TDF/FTC was associated with a 0.6-kg (95% CI: 0.1 to 1.1) per 6-months greater gain. Weight gain on dolutegravir/abacavir/FTC and darunavir/TDF/FTC was significantly greater than that for several integrase inhibitor-based regimens. Conclusions: There is heterogeneity between regimens in weight gain following ART initiation among previously ART-naïve PLWH; we observed greater gain among PLWH taking newer integrase strand transfer inhibitors (DTG, BIC) and DRV-based regimens.

Assessment of Obesity and Cardiometabolic Status by Integrase Inhibitor Use in REPRIEVE: A Propensity-Weighted Analysis of a Multinational Primary Cardiovascular Prevention Cohort of People With Human Immunodeficiency Virus

“…Our data extend findings from prior studies demonstrating greater weight gain associated with INSTI-based regimens as observed in several cohort studies and RCTs including ADVANCE [ 4 , 6 ], NAMSAL [ 13 ], and other studies [ 3 , 5 , 7 , 14–16 ]. Our analysis has one of the largest sample sizes to date and includes a multinational population.…”

Excess Weight Gain With Integrase Inhibitors and Tenofovir Alafenamide: What Is the Mechanism and Does It Matter?

“…Data demonstrating INSTI-associated excess weight gain have most consistently implicated DTG and BIC; fewer studies have demonstrated an association with raltegravir (RAL) or elvitegravir/cobicistat (EVG/c) [ 55–64 ]. Several analyses have found that individuals born female have greater likelihood of INSTI-associated weight gain than individuals born male [ 16 , 56 , 61 ].…”

“…It has been argued that the exaggerated weight gain identified when comparing INSTIs with other classes may stem from viral kinetics and faster viral load reduction with INSTIs, leading to faster or more pronounced return-to-health changes. However, several studies that analyzed differences in weight over time after initiation of INSTIs vs other agents found differential weight gain at time points when the viral suppression rates were equivalent, so this seems unlikely to be the explanation [ 55 , 62 ].…”

Apples to Apples? A Comparison of Real-World Tolerability of Antiretrovirals in Patients with Human Immunodeficiency Virus Infection and Patients with Primary Biliary Cholangitis

“…The newer formulation, tenofovir alafenamide (TAF), does not cause renal dysfunction but is associated with weight gain, an unwanted side effect in those with normal or elevated weight prior to starting therapy. Indeed, weight gain appears to be amplified with TAF in combination with second-generation integrase strand transfer inhibitors (INSTIs) such as dolutegravir or bictegravir [ 47 , 48 , 49 , 50 ]. Unlike some other antiretroviral drug classes, NRTIs are not specifically linked with diarrhea or other GI symptoms [ 51 ].…”

“…Dolutegravir and bictegravir are also both available in coformulations with NRTIs as single-tablet regimens for HIV treatment. While weight gain can occur after the initiation of any antiretroviral regimen and is at least in part associated with the “return to health” phenomenon, there is a clearly delineated association between the initiation of INSTI-based regimens—particularly dolutegravir and bictegravir—and weight gain compared with PI and NNRTI regimens [ 47 , 48 , 49 , 72 , 73 , 74 , 75 ]. Enhanced weight gain is a particular challenge in a population where diabetes, cardiovascular disease and other metabolic conditions are more prevalent than in the general population [ 72 ].…”