Background:
Data on the effect of dual therapy with DTG/3TC as first-line ART on the evolution of the HIV-1 reservoir and inflammatory biomarkers are lacking. Our objective was to compare the effect of first-line ART with DTG+3TC versus one standard 3-drug regimen (3DR) on the dynamics of viral persistence in lymph nodes and peripheral blood and on immune activation biomarkers during the 1st year after ART initiation. Here, we present data on the evolution of HIV persistence and immune-associated parameters in peripheral blood.
Methods:
DUALITY is a 48-week, single-centre, randomized, open-label clinical trial in ART-naïve people with HIV (PWH). Participants were randomized (1:1) to receive DTG+3TC (2DR group), or with DTG+FTC/TAF (3DR group). Total and intact proviral HIV-1 DNA and cell-associated RNA (ca-RNA) in CD4+ T cells were longitudinally determined by ddPCR. The inducible reservoir was measured as the frequency of HIV-infected CD4+ T cells able to produce p24 by the VIP-SPOT assay. Soluble inflammatory markers (IL-6, sCD14, TRAIL, IP10, FABP2, CRP and D-dimer) were quantified by ELISA. Activation (HLA-DR/CD38) and exhaustion markers (PD-1/TIGIT) in CD4+ and CD8+ T cells were determined by multiparametric flow cytometry.
Results:
Fourty-for participants were included (22 per study arm). At baseline, mean (SD) log10 pVL and CD4+ T cell count were 4.4 (0.7) copies/mL and 493 (221) cells/mm3. Two participants were lost, and one withdrew informed consent before week 48. All participants completing the study (2DR n=20; 3DR n=21) had pVL <50 copies/mL at week 48, except one in the 2DR group who was resuppressed after treatment for syphilis. Changes from baseline to week 48 in all reservoir parameters were similar between 2DR and 3DR groups (Table). At week 48, levels of total and intact proviruses were similar between both groups, and correlated with pre-ART pVL (Rho 0.50, p=0.002 for intact HIV-1 DNA). Changes in soluble inflammatory biomarkers and in levels of activated/exhausted CD4+ and CD8+ T cells were also comparable between study groups. Complementary data on anatomic distribution of antiretroviral drugs and viral expression in lymph nodes are under study.
Conclusions:
First-line dual ART with DTG+3TC resulted in a similar decay in parameters of HIV-1 persistence in periphery as well as in immune-associated markers compared to 3DR with DTG+FTC/TAF. Our results further support recommendation of DTG/3TC as one preferred option for first-line ART in PWH.
