Cardiometabolic impact of dolutegravir as second-line therapy: secondary analysis of a randomized controlled trial

Objectives: To examine changes in weight after initiating different dolutegravir-based second-line antiretroviral regimens and to measure the impact of observed weight change on blood pressure and serum lipids. Design: Secondary analysis of the D2EFT trial, a randomised open-label trial in people with HIV Methods: In D 2 EFT, ritonavir-boosted darunavir plus dolutegravir (DTG + DRV/r) and dolutegravir with tenofovir disoproxil fumarate plus either lamivudine or emtricitabine (DTG + TDF/XTC) were compared to ritonavir-boosted darunavir plus two nucleoside reverse transcriptase inhibitors (DRV/r + 2NRTIs). We used linear mixed effects models for weight, blood pressure and lipid changes and generalized estimating equations for ≥5% weight gain. Results: 826 participants were included. Significantly greater body weight and BMI gains at 48 and 96 weeks were observed in individuals taking DTG + DRV/r or DTG + TDF/XTC than in individuals taking DRV/r + 2NRTIs. Treatment arm (DTG + DRV/r and DTG + TDF/XTC), female gender, Black and Hispanic/Latino ethnicity, lower baseline CD4 count, and higher baseline HIV RNA were all associated with weight gain in multivariable analysis. There was no significant difference between treatment arms in blood pressure changes at 96 weeks after adjustment for weight gain. Both darunavir containing arms demonstrated greater increases in LDL cholesterol than DTG + TDF/XTC, with the greatest increase in the non-NRTI containing arm. Conclusions: Dolutegravir-based second-line regimens were associated with weight gain, which was further influenced by gender, ethnicity and HIV-related factors. DTG-based second-line regimens had no significant effect on blood pressure at 96 weeks; DTG + TDF/XTC was associated with a more favourable lipid profile than darunavir-containing regimens. Clinical Trial Registration number: NCT03017872