CD4 and HIV-1 infection: Desai and Landay propose a multifaceted model for accelerated aging in HIV-1 infection (13): residual HIV-1 replication in activated immune cells despite ART; HIV-1 depletion of Th17 lymphocytes at GI epithelial mucosa causes microbial translocation and antigenic burden; thymic dysfunction causes loss of naïve T lymphocytes and regulatory CD4+ T lymphocytes, suppressing T lymphocyte activation; clonal expansion of activated immune cells with T lymphocyte loss of CD28 and telomere shortening, causing non-functional, senescent T lymphocytes (9, 14–17).