ART reduces T cell activation and immune exhaustion markers in HIV controllers

BACKGROUND: Despite low plasma HIV RNA, HIV controllers have evidence of viral replication and elevated inflammation. We assessed the effect of antiretroviral therapy (ART) on HIV suppression, viral reservoir, immune activation, and quality of life in this population. METHODS: A5308 was a prospective, open-label study of rilpivirine/emtricitabine/tenofovir disoproxil fumarate in ART-naïve HIV controllers (N=35), defined as having HIV RNA < 500 copies/mL for =12 months. The primary outcome measured change in %CD38+HLA-DR+ CD8+ T cells. Residual plasma viremia was measured by the integrase single-copy assay (iSCA) and reservoir size by total HIV DNA in CD4+ T cells. Quality of life (QoL) was measured by the EQ-5D questionnaire. Outcomes were evaluated by repeated measures GEE models. RESULTS: Before ART, HIV controllers with undetectable residual viremia < 0.6 HIV-1 RNA copies/mL had higher CD4+ counts and lower levels of T cell activation than those with detectable residual viremia. ART use was effective in further increasing the proportion of individuals with undetectable residual viremia (pre-ART vs. after 24-48 weeks of ART: 19% vs. 94%, P< 0.001). Significant declines were observed in the %CD38+HLA-DR+CD8+ T cells at 24-48 (-4.0%, P=0.001) and 72-96 (-7.2%, P< 0.001) weeks after ART initiation. ART use resulted in decreases of several cellular markers of immune exhaustion and in a modest but significant improvement in self-reported QoL. There were no significant changes in CD4+ counts or HIV DNA. CONCLUSIONS: ART in HIV controllers reduces T cell activation and improves markers of immune exhaustion. These results support the possible clinical benefits of ART in this population.

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