DISTRIBUTION AND REDUCTION MAGNITUDE OF HIV-DNA BURDEN IN CD 4 + T CELL SUBSETS DEPEND ON ART INITIATION TIMING Running head : HIV-DNA in CD 4 + T-cell subsets on ART

Objective: The aim of our study was to analyze the dynamics of HIV-DNA levels in CD4+ Tcell subsets in individuals starting successful dolutegravir-based regimens. Design: Twenty-seven individuals with acute (AI, n=8) or chronic (CI, n=5) infection and patients in virological success (VS, n=10) or failure (VF, n=4) on ART who initiated a dolutegravir-based regimen were enrolled (NCT02557997). Methods: CD4+ T-cells from baseline and week 48 of successful treatment were sorted into effector memory (TEM), transitional memory (TTM), central memory (TCM) and naïve (TN) cell groups for total HIV-DNA measurements by qPCR. Bayesian methods were used to estimate the posterior probability of a HIV-DNA decrease >0.25 log copies/10 cells at week 48. Results: All patients achieved HIV-RNA suppression at 48 weeks. At baseline and week 48, the highest contributions to the HIV-DNA-infected pool from CD4+ T-cells were observed in TTM cells in the AI group (62.4% and 60.2%, respectively), but in TCM cells for the CI, VS and VF groups (54.6% and 59.4%, 58.2% and 62.9%, 62.4% and 67.2%), respectively. HIV-DNA burden declined in all subsets after 48 weeks of treatment in the AI (probability (Pr)>91%), CI (Pr>52%) and VF (Pr>52%) groups, but only in TEM cells in the VS group (Pr=95%). Conclusions: Our study showed that dolutegravir-based treatment reduced the HIV-DNA cellular burden in individuals from the AI, CI and VF groups, though the reduction levels differed between the patient subgroups. Early treated patients had the highest probability of HIVDNA reduction. Interestingly, in the aviremic VS group, HIV-DNA reduction was limited to TEM cells. Copyright © 2018 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.