HIV controllers suppress viral replication and evolution and prevent disease progression following intersubtype HIV-1 superinfection.
Published in AIDS, 2018
Abstract
OBJECTIVE:To investigate the impact of intersubtype HIV-1 superinfection (SI) on viremia, reservoir reseeding, viral evolution, and disease progression in HIV controllers (HIC). DESIGN:Longitudinal analysis of two Brazilian HIC subjects (EEC09 and VC32) previously identified as dually infected with subtypes B and F1 viruses. METHODS:Changes in plasma viremia, total HIV-1 DNA levels, CD4 T cell counts and HIV-1 quasispecies composition were measured over time. HIV-1 env diversity in PBMC and plasma samples was accessed by single genome amplification and next-generation sequencing approaches, respectively. Viral evolution was evaluated by estimating nucleotide diversity and divergence. RESULTS:Subject EEC09 was probably initially infected with a CCR5-tropic subtype B strain and sequentially superinfected with a CXCR4-tropic subtype B strain and with subtype a F1 variant. Subject VC32 was infected with a subtype B strain and superinfected with a subtype F1 variant. The intersubtype SI events lead to a moderate increase in viremia and extensive turnover of viral population in plasma but exhibited divergent impact on the size and composition of cell-associated HIV DNA population. Both subjects maintained virologic control (<2,000 copies/mL) and presented no evidence of viral evolution or immunologic progression for at least two years after the intersubtype SI event. CONCLUSION:These data revealed that some HIC are able to repeatedly limit replication and evolution of superinfecting viral strains of a different subtype with no signs of disease progression.
