Lower HIV reservoir size in individuals who maintain higher CD4+ T cells counts prior to antiretroviral therapy initiation: the Strategic Timing of Antiretroviral Treatment (START) HIV reservoir study


BACKGROUND: HIV cure strategies may be enhanced by identifying factors that determine the frequency of latently infected CD4+ T cells on antiretroviral therapy (ART). We investigated the role of the CD4+ T cell count in people initiating ART with > 500 CD4 cells/mm3 for HIV persistence on ART.
METHODS: In this study nested within START, we enrolled people with HIV (PWH) who were randomised to commence immediate ART at enrolment with CD4+ T cell counts of either 500-599, 600-799 or '¥800 cells/mm3. Samples for HIV reservoir analyses were collected after 36-44 months on ART. Total HIV DNA, cell-associated unspliced HIV-RNA (CA-US HIV RNA) and 2-long terminal repeat HIV DNA in CD4+ T cells and measured plasma HIV RNA by single-copy assay were quantified We measured T cell expression of HLA-DR, programmed death-1 (PD-1) and phosphorylated signal transducer and activator of transcription-5 (pSTAT5). Virological and immunological measures were compared across CD4+ strata and analysed for associations with clinical characteristics at ART initiation.
RESULTS: A total of 146 study participants were enrolled, 36 in the 500-599, 60 in the 600-799 and 50 in the '¥800 CD4+ T cell strata. Of these, 59 (40%) were males, 87 (60%) were females, 124 (89%) were Black and 20 (13.7%) were Hispanic. Following 36-44 months of ART, total HIV DNA, plasma HIV RNA and HLA-DR expression was significantly lower in PWH with CD4+ T cell count '¥800 cells/mm3 at ART initiation compared to 600-799 or 500-599 cells/mm3. Expression of pSTAT5 did not differ across CD4+ strata but was highly correlated with lower levels of HIV DNA and CA-US HIV RNA. Virological measures were significantly lower in females compared to males.
CONCLUSIONS: We report that commencing ART with a CD4+ T cell count '¥800 cells/mm3 compared to 600-799 or 500-599 cells/mm3 was associated with a significantly lower level of total HIV DNA, plasma HIV RNA and T cell activation after 36-44 months of suppressive ART. Our study revealed considerable differences between women and men in measures of HIV persistence and that pSTAT5 is associated with a reduced frequency of latently infected cells.