Randomized clinical trial to evaluate the longitudinal HIV-1 reservoir and inflammation in treatment-naïve people starting dolutegravir/lamivudine versus dolutegravir plus tenofovir alafenamide/emtricitabine

Objective There is limited evidence on whether dolutegravir/lamivudine (DTG/3TC) reduces the viral reservoir, immune activation, and inflammation as a three-drug regimen. This study aims to clarify possible differences in these outcomes in PHIV starting DTG plus tenofovir alafenamide/emtricitabine (DTG+TAF/F) versus DTG/3TC. Methods A phase IV, controlled, open-label, multicenter clinical trial in which treatment-naïve PHIV were randomized to DTG+TAF/F or DTG/3TC. The primary endpoint was changes in CD4 + T-cells associated HIV-1-DNA and -RNA after 12 and 24 months (Intact Proviral DNA and Intact Viral RNA Assays). Secondary endpoints included immune recovery and changes in T cell phenotypes and plasma inflammatory markers. Statistics: χ 2 , Mann-Whitney U test, and general linear model for repeated measures. Results Sixty-six participants were randomized, of whom 30 (DTG/3TC) and 29 (DTG +TAF/F) completed follow-up. Overall, the median baseline CD4 + /μL count was 401 (293-540), the CD4 + /CD8 + ratio 0.47 (0.34-0.76), and the viral load 57,250 copies/mL (16,189-180,500) Results are reported as medians (interquartile ranges) in the DTG+TAF/F and DTG/3TC groups at baseline and month 24, respectively. Intact HIV-1-DNA: 1,210 (412-3,508) copies/10 6 CD4 + and 1,230 (335-2,502), which decreased to 65 (24-236) and 71 (32-110) (F= 0.253; p=0.691). Total defective HIV-1-DNA: 831 copies/10 6 CD4 + (315-1636) and 726 (273-1770), decreasing to 143 copies/10 6 CD4 + (82-368) and 266 (67-353) (F= 1.840, p=0.201). Likewise, no significant differences were observed between the groups in immune recovery, decrease in activation, proliferation, and exhaustion markers of T-cells, as well as in the reduction of plasma levels of IL-1β, IL-6, TNF-α, IFN-γ, sCD14, and sCD163. Conclusions These data suggest that starting treatment with DTG+TAF/F does not confer benefits over DTG/3TC.