Extremely low viral reservoir in treated chronically HIV-1-infected individuals

BACKGROUND: Small viral reservoirs are found predominantly in HIV-1 controllers and individuals treated during acute/early HIV-1 infection. However, other HIV(+) individuals could naturally also harbour low viral reservoirs. METHODS: We screened 451 HIV-1-infected treated-individuals with suppressed plasma viremia for at least 3 years and stored cryopreserved peripheral blood mononuclear cells (PBMCs). Total HIV-DNA was analysed in PBMCs with ddPCR. Individuals with <50 HIV-DNA copies/10(6) PBMCs constitute the ‘Low Viral Reservoir Treated’ cohort (LoViReT). Longitudinal samples were obtained from 12 chronically treated LoViReT and compared to 13 controls (>50 HIV-DNA copies/10(6) PBMCs) to analyse total HIV-DNA, T-cell and NK-cell populations, HIV-1 specific antibodies, and plasma inflammation markers. FINDINGS: We found that 9.3% of the individuals screened had <50 HIV-DNA copies/10(6) PBMCs. At least 66% initiated cART during the chronic phase of HIV-1 infection (cp-LoViReT). Cp-LoViReT harboured lower levels of HIV-DNA before cART and after treatment introduction the decays were greater compared to controls. They displayed a marked decline in quantity and avidity in HIV-specific antibodies after initiation of cART. Cp-LoViReT had fewer CD8(+) T(TM) and T(EMRA) in the absence of cART, and higher CD8(+) T(N) after 18 months on therapy. INTERPRETATION: Treated chronically HIV-1-infected LoViReT represent a new phenotype of individuals characterized by an intrinsically reduced viral reservoir, less impaired CD8(+) T-cell compartment before cART, and low circulating HIV-1 antigens despite being treated in the chronic phase of infection. The identification of this unique group of individuals is of great interest for the design of future eradication studies. FUNDING: MSD Spain