No change in body weight with switching antiretroviral regimens in those who experience weight gain on integrase inhibitors
Presenter: William Short, MD, Perelman School of Medicine, University of Pennsylvania, Philadelphia
A prospective, randomized trial to assess a protease inhibitor-based regimen switch strategy to manage integrase inhibitor-related weight gain. Presented July 25,2023.
No significant change in body weight was observed 24 weeks after switching from an integrase strand transfer inhibitor (INSTI)-based regimen to darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/FTC/TAF) among adults with HIV-1 infection who had gained at least 10% of body weight during INSTI therapy. Findings were consistent across multiple endpoints, including body mass index (BMI) and waist circumference, and among key subgroups, according to findings from the phase 4 DEFINE study. The results were presented by William Short, MD, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
“INSTI-based antiretroviral therapies are associated with greater weight gain than non-nucleoside reverse transcriptase inhibitor or boosted protease inhibitor-based regimens, and these effects disproportionately impact Black and Hispanic individuals and women living with HIV-1,” said Dr. Short. “The mechanisms underlying INSTI-related weight gain are unknown, and whether this weight gain can be mitigated or reversed by switching antiretroviral classes is unclear and under investigation.”
DEFINE is a randomized active-controlled open-label multicenter study that enrolled 103 virologically suppressed adults with HIV and with at least a 10% increase in body weight within a 36-month period on an INSTI-plus-tenofovir alafenamide and emtricitabine (TAF/FTC) antiretroviral regimen. Patients were randomized to an early switch to D/C/FTC/TAF or to remain on an INSTI plus TAF/FTC. Strategies were implemented to ensure a diverse study population representative of women and Black people living with HIV-1, and 30% of the study participants were women and 61% were Black. Participants who initiated or discontinued concomitant medications associated with substantial weight change within 90 days of screening were excluded. The median age of study participants was 45.0 years, and their median body mass index was 32.7 kg/m2. The median percent weight they had gained on their current antiretroviral regimen at baseline was 14.2%. Most participants (81%) were on a bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) regimen at baseline.
There was no significant difference in weight change through 24 weeks after switching from an INSTI-based regimen to D/C/FTC/TAF. In those who switched early, the mean percent change in body weight from baseline to week 24 was a 0.63% increase, whereas those who remained on INSTI had a mean 2.4% decrease in body weight compared with baseline (P = .2394). Most participants in each study arm had body weight changes of 3% or less, and most remained within their baseline BMI and waist circumference categories.
Changes in body weight at week 24 were consistent among key subgroups that included those with a baseline BMI 30 kg/m2 or more, women, men, Black/African American, non-Black/African American, and Black/African American women. Body composition by dual-energy x-ray absorptiometry was stable over time in both study arms.
Efficacy at week 24 was maintained across both study arms. CD4+ cell counts were relatively stable over time and similar between arms. At week 24, virologic failure (HIV-1 RNA ≥ 50 copies/mL) was observed in 5 participants in the INSTI-plus-TAF/FTC arm and none in the D/C/FTC/TAF arm. Switching to D/C/FTC/TAF was safe and well tolerated.
The results are notable, given the limited head-to-head comparison data available for boosted darunavir versus INSTIs, said Dr. Short. “Although the DEFINE study is ongoing, results at week 24 suggest that INSTI-related weight gain may not be reversible through antiretroviral switch and highlight the importance of including body weight and associated risk factors for metabolic health as pretreatment considerations,” he added.
Dr. Short consults for Gilead Sciences, Inc. and has received honoraria from ViiV Healthcare. The DEFINE study was funded by Janssen Scientific Affairs, LLC.