Switching antiretroviral regimens does not help with weight loss

Switching from an integrase inhibitor (INI)-based antiretroviral treatment (ART) regimen to a protease inhibitor (PI)-based regimen falls short of reversing weight gain while on the INI-based regimen, according to the results of the open-label phase IV DEFINE trial.

DEFINE included 103 virologically suppressed HIV-1-infected adults who had gained at least 10 percent of their body weight while on the INI-based regimen. Those who switched to a PI-based regimen had similar percent change in body weight from baseline to week 24, which was the primary endpoint, as those who remained on the INI-based regimen, reported principal investigator Dr William Short of Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States.

Over 24 weeks, body weight increased by 0.63 percent for switchers and decreased by –0.24 percent for nonswitchers (p=0.2394). [IAS 2023, abstract 5962]

“Most participants in each arm had body weight changes of not more than 3 percent and remained within baseline body mass index (BMI) and waist circumference categories,” Short noted.

“Importantly, this study included a high representation of women and Black people living with HIV-1, and similar body weight changes were seen across treatment arms within these important subgroups at increased risk of weight gain,” he added.

The changes in body weight at week 24 were consistent in the following subgroups: BMI (≥30 kg/m2: –0.34 percent vs 0.25 percent), sex (female: 0.73 percent vs 0.16 percent; male: 0.43 percent vs 0.99 percent), and race (Black/African American: –0.15 percent vs 0.16 percent; non-Black/African American: 0.66 percent vs 0.51 percent; Black/African American female: 0.03 percent vs 0.18 percent).

“Body composition by dual X-ray absorptiometry (DEXA) was stable over time for both study arms,” with DEXA measurements of fat mass, lean body mass, total mass, and appendicular and visceral fat showing minimal changes from baseline to week 24 and between the participants who switched from and remained on the INI-based regimen, Short said.

In terms of efficacy, virologic suppression and CD4+ cell counts were maintained in switchers and nonswitchers, according to Short. At week 24, virologic failure (HIV-1 RNA ≥50 copies/mL) was documented in five participants who continued with their INI-based regimen and in none of those who switched to a PI-based regimen.

Finally, switching to a PI-based regimen was safe and well tolerated, with a similar frequency of adverse events (AEs) between switchers and nonswitchers (57 percent vs 62 percent). Of note, gastrointestinal AEs were reported in 17 percent and 16 percent of participants, respectively.

“Although the DEFINE study is ongoing, results at week 24 suggest that INI-related weight gain may not be reversible through ART switch and highlight the importance of including body weight and associated weight risk factors for metabolic health as pretreatment considerations,” according to Short.

“These results are notable given the limited head-to-head comparison data available for boosted darunavir versus INIs,” he added.

DEFINE included 103 participants (median age 45.0 years, 30 percent women, 61 percent Black, median BMI 32.7 kg/m², median body weight 100.2 kg). Of these, 53 comprised the treatment arm assigned to switch to darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) while 50 were included in the arm assigned to continue with INI+TAF/emtricitabine. At 24 weeks, >90 percent of the participants were still in the study.