Switch to PI-based ART may reverse INSTI-related weight gain in HIV

For patients with HIV infection who experience weight gain on integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART), weight loss may occur over time after switching to protease inhibitor (PI)-based ART with darunavir (DRV)/cobicistat (c)/emtricitabine (FTC)/tenofovir alafenamide (TAF). These findings were published in Clinical Infectious Diseases.

Previous research suggests that INSTI-based ART is associated with weight gain in patients with HIV infection. Therefore, researchers conducted a randomized, open-label, prospective, phase 4 study (ClinicalTrials.gov identifier: NCT04442737) to determine whether a switch to PI-based ART can mitigate or reverse INSTI-related weight gain.

The study included patients (N=103) who were virologically suppressed and experienced a 10% or greater increase in body weight within the previous 36 months while on INSTI-based ART with TAF/FTC. Data for the analysis were captured across 28 sites in the United States between 2020 and 2023. Patients were randomly assigned 1:1 to either switch to fixed-dose DRV/c/FTC/TAF for 48 weeks (n=53) or remain on INSTI-based ART with TAF/FTC for 24 weeks and then switch regimens for weeks 24 through 48 (n=50). The primary endpoint was the change in body weight from baseline to 24 weeks, with a percent change in body weight of more than 5% defined as a clinically meaningful.

Among patients who switched to PI-based ART vs continued INSTI-based ART, the median ages were 42 (IQR, 22-73) vs 49 (IQR, 22-69) years, 30% vs 30% were women, 62% vs 60% were Black, 52.8% vs 78.0% had obesity, and the median duration of INSTI-based ART with TAF/FTC was 2.3 (IQR, 0.7-5.8) vs 2.5 (IQR, 0.6-5.7) years.

In patients who continued INSTI-based ART, median BMI increased from baseline to week 24 (from 34.7 [IQR, 30.8-40.1] to 35.2 [IQR, 30.0-40.7] kg/m²). In patients who switched to PI-based ART, reductions from the median BMI recorded at baseline (31.4 [IQR, 27.6-39.0] kg/m²) were observed at 24 weeks (30.9 [IQR, 28.0-37.6] kg/m²) and at 48 weeks (30.4 [IQR, 27.6-37.9] kg/m²).

The rate of clinically meaningful weight loss was 11% in patients who remained on INSTI-based ART and 4% and 24% among those who switched to PI-based ART at weeks 24 and 48, respectively.

The occurrence of weight loss among patients who switched to PI-based ART was more evident with prolonged use. The median percent change in body weight increased over time (0-24 vs 24-48 weeks), particularly in those with a BMI of 30 kg/m² at baseline (-0.34% vs -1.07%), women (0.73% vs -1.75%), men (0.43% vs -0.82%), Black patients (-0.15% vs -1.11%), and non-Black patients (0.66% vs -0.84%).

In regard to safety, patients who switched to PI-based ART and those who continued INSTI-based ART exhibited similar rates of adverse events between baseline and 24 weeks (57% and 58%, respectively). The most common adverse events included COVID-19 infection, hypertension, diarrhea, and nausea.

Study limitations include the relatively small sample size and the imbalance in BMI between the groups at baseline.

According to the researchers, “Additional studies with longer follow-up are warranted to continue exploring the impact of treatment switching on ARV [antiretroviral]-related weight gain in PLWH [people living with HIV].”

Disclosure: This study was supported by Janssen Scientific Affairs, LLC., and multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

By Jessica Nye, PhD

References:

Anderson D, Ramgopal M, Hagins DP, et al. DEFINE: a prospective, randomized, phase 4 trial to assess a protease inhibitor–based regimen switch strategy to manage integrase inhibitor–related weight gain. Clin Infect Dis. Published online September 4, 2024. doi:10.1093/cid/ciae449