Objective: To compare the effects of first-line antiretroviral treatment (ART) with dolutegravir plus lamivudine (DTG+3TC) versus DTG plus emtricitabine/tenofovir alafenamide (FTC/TAF) on the evolution of the HIV-1 reservoir and immune activation biomarkers in people with HIV (PWH).
Methods: DUALITY was a 48-week, single-center, randomized, open-label clinical trial in ART-naïve PWH. Participants were randomized (1:1) to receive ART with DTG+3TC (2DR group) or DTG+FTC/TAF (3DR group). Total and intact proviral HIV-1 DNA, cell-associated RNA in CD4+ T cells, the frequency of HIV-infected CD4+ T cells able to produce p24, plasma soluble inflammatory markers (IL-6, sCD14, TRAIL, IP-10, FABP2, CRP and D-dimer), and activation and exhaustion markers in CD4+ and CD8+ T cells were longitudinally determined.
Results: Forty-four participants (22 per study arm) were enrolled. Baseline mean (SD) log10 plasma viral load (pVL) and CD4+ T cell counts were 4.4 (0.7) copies/mL and 493 (221) cells/mm3, respectively. All participants completing the study (2DR n=20; 3DR n=21) had pVL <50 copies/mL at week 48, except for one in the 2DR group who was resuppressed after treating syphilis. Changes from baseline to week 48 in all reservoir parameters or in levels of soluble inflammatory biomarkers and activated or exhausted CD4+ and CD8+ T cells were similar between 2DR and 3DR groups.
Conclusion: First-line ART with DTG+3TC resulted in a similar reduction of HIV-1 persistence parameters in peripheral blood, and comparable changes in immune-associated soluble and T-cell markers compared with DTG+FTC/TAF. These findings support recommendation of DTG/3TC among preferred options for first-line ART in PWH.
Keywords: Dolutegravir/lamivudine; Dual antiretroviral therapy; HIV infection; HIV reservoir.
This study, named DUALITY, looked at how two different initial HIV treatments affect the amount of hidden HIV in the body and immune system activity. The treatments compared were dolutegravir plus lamivudine (DTG+3TC) and dolutegravir plus emtricitabine/tenofovir alafenamide (DTG+FTC/TAF). The study included 44 people with HIV who had never been treated before. Participants were randomly assigned to one of the two treatments and followed for 48 weeks. The amount of HIV in the participants’ CD4+ T cells, as well as markers of immune system activity and inflammation were measured during the study. By the end of the study, almost all participants had their viral load reduced to very low levels, regardless of which treatment they received. Also, there were no significant differences between the two treatment groups in terms of reducing hidden HIV or changes in immune system markers. Overall, the study showed that both treatments were equally effective, supporting the use of DTG+3TC as a preferred option for initial HIV treatment.
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