BACKGROUND: Integrase inhibitor (INI)-based antiretroviral (ARV) therapies are associated with greater weight gain than non-nucleoside reverse transcriptase inhibitor- or boosted protease inhibitor-based regimens, disproportionately affecting Black and Hispanic individuals and women. There are no prospective, randomized data exploring the impact of switching ARV classes to mitigate or reverse ARV-related weight gain.
METHODS: DEFINE (ClinicalTrials.gov: NCT04442737) is a randomized (1:1), prospective, 48-week, active-controlled, open-label, multicenter phase 4 study evaluating switching to darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) versus continuing INI+TAF/emtricitabine (FTC) in virologically-suppressed HIV-1-infected adults who had =10% weight gain while on the INI-based regimen. The primary objective was to assess percent change in body weight from baseline to Week 24 in both arms. Data through Week 24 are reported.
RESULTS: Overall, 103 adults were randomized to D/C/F/TAF (n=53) or continued INI+TAF/FTC (n=50); 30% were female and 61% were Black/African American (Table). At Week 24, there was no significant difference in percent change in body weight from baseline between the D/C/F/TAF and INI+TAF/FTC arms (Figure 1A). Most participants in each arm had body weight changes of =±3% and remained within baseline body mass index and waist circumference categories. Percent body weight changes for key subgroups are shown in Figure 1B. Switching to D/C/F/TAF was safe and well tolerated, and efficacy was maintained.



CONCLUSIONS: There was no significant difference in weight change through 24 weeks after switching from an INI-based regimen to D/C/F/TAF in adults with INI-related weight gain. Additional analyses are ongoing, including follow up through Week 48 and evaluation of changes in biomarkers and body composition (DEXA).