Abstract Body

Small-size viral reservoirs are predominantly found in HIV-1 controllers and individuals treated during acute/early HIV-1 infection. However, other HIV+ subjects could naturally also harbor low viral reservoirs. We have established a cohort of "Low Viral Reservoir Treated" subjects" (LoViReT) to further explore the mechanisms associated with low reservoir levels.

42 HIV+ subjects on ART and <50 HIV-DNA copies/106 PBMCs constitute the LoViReT cohort; at least 66% of whom initiated ART during the chronic phase of HIV (>6 months since acquisition). In 12 LoViReTs, total HIV-DNA was longitudinally measured in cryopreserved CD4+ T cells by ddPCR, including a pre-ART time point. 14 LoViReTs underwent a leukapheresis to measure the replication-competent virus by qVOA (37×106 CD4+ T cells), and total HIV-DNA in sorted CD4+ T cell subsets. In 9 LoViReTs with <0.1 infectious units per million (IUPM), total HIV-DNA was measured in rectal and/or lymph node biopsies (LN). Clinically matched individuals with HIV-DNA >50 HIV-DNA copies/106 PBMCs were recruited as controls.

LoViReT harbored significantly lower total HIV-DNA in CD4+ T cells before ART initiation compared to controls (1,051 and 5,995 HIV-DNA copies/106 CD4+ T cells respectively, p=0.002) despite comparable pre-ART viral load. These differences became higher after 5 years on ART (16 vs 5-folds decay respectively, p<0.001). 10/14 LoViReTs had undetectable replication-competent virus (IUPM<0.0185) >10 years after ART. Among them, we detected low levels of HIV-DNA in rectum in 6/8 subjects with a median of 57 HIV-DNA copies/106 CD45+ T cells [IQR:37-114]. In LN, only 3/8 subjects had detectable reservoir (263[36-2,112] HIV-DNA copies/106 CD45RA T cells). Unexpected HIV reservoir distribution was observed in LoViReTs, being the short-live transitional memory (TTM) and effector memory (TEM) T cells the major contributors to the total reservoir (47% and 29% respectively). TCM presented limited contribution to the HIV reservoir (24%).

LoViReT individuals have abnormally low HIV reservoirs before ART initiation. 71% of LoViReTs did not have replication-competent virus and harbored limited provirus in tissue sanctuaries after a median of 15 years on ART. A cause of this exceptional low reservoir could be the high contribution of the short-live TTM and TEM cells in the total HIV reservoir. This unique group of individuals are of great interest as trial participants in eradication studies.