Georg Behrens

In PASO-DOBLE, switch to either DTF/3TC or BIC/FTC/TAF led to a significant increase in mean adjusted weight when on BIC/FTC/TAF compared to DTG/3TC but this was influenced by pre-switch TDF. The DEFINE Study shows that weight gain during integrase inhibitor therapy is difficult to revers with a switch to D/C/F/TAF.

In PASO-DOBLE, n=553 people with a median BMI of about 25 kg/m2 switched from their current regimen to either DTF/3TC or BIC/FTC/TAF. At 48 weeks, DTG/3TC was virologically non-inferior to BIC/FTC/TAF, but the mean adjusted weight increased significantly more with BIC/FTC/TAF (1.81kg, 95%CI 1.28-2.34) than with DTG/3TC (0.89kg, 95%CI 0.37-1.41). Interestingly, >5% weight gain in BIC/FTC/TAF varied by pre-switch NRTI and was more prevalent in those switching from TDF, followed by ABC. Any options for adults who had experienced ≥10% weight gain on an integrase strand transfer inhibitor (InSTI)–based antiretroviral regimen? In the DEFINE Study, a trend towards weight loss was observed at 48 weeks post–switch to darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF), including across key participant subgroups. Looking at the liver, PNPLA3 rs738409 CG/GG vs CC genotype is a known risk factor steatotic liver disease (SLD) and increased the risk of for SLD in lean people with HIV, but not in overweight/obese individuals. People with HIV with insomnia who switched from DTG to BIC-ART had improvements in brain function parameters (scores for sleep and quality of life), when compared to those on dolutegravir-ART.

PASO-DOBLE provides new evidence on the efficacy and safety of DTG/3TC versus BIC/FTC/TAF as maintenance antiretroviral therapy, but the evidence that TAF causes more weight gain remains indirect, since the intervention also was a switch away from TDF. In DEFINE 60% of participants were African Americans and only 103 participants were randomized. More importantly, the clinical relevance of a loss of -0.36% from baseline body weight after switch of the control arm is questionable. The CNS trial randomized just 19 participants but it provides some evidence for addressing DTG-associated insomnia.