Longitudinal study reveals HIV-1–infected CD4+ T cell dynamics during long-term antiretroviral therapy
Year: 2020
Type: article
Study design: Observational Study
Abstract: Proliferation of CD4+ T cells harboring HIV-1 proviruses is a major contributor to viral persistence in people on antiretroviral therapy (ART). To determine whether differential rates of clonal proliferation or HIV-1-specific cytotoxic T lymphocyte (CTL) pressure shape the provirus landscape, we performed an intact proviral DNA assay (IPDA) and obtained 661 near-full-length provirus sequences from 8 individuals with suppressed viral loads on ART at time points 7 years apart. We observed slow decay of intact proviruses but no changes in the proportions of various types of defective proviruses. The proportion of intact proviruses in expanded clones was similar to that of defective proviruses in clones. Intact proviruses observed in clones did not have more escaped CTL epitopes than intact proviruses observed as singlets. Concordantly, total proviruses at later time points or observed in clones were not enriched in escaped or unrecognized epitopes. Three individuals with natural control of HIV-1 infection (controllers) on ART, included because controllers have strong HIV-1-specific CTL responses, had a smaller proportion of intact proviruses but a distribution of defective provirus types and escaped or unrecognized epitopes similar to that of the other individuals. This work suggests that CTL selection does not significantly check clonal proliferation of infected cells or greatly alter the provirus landscape in people on ART.
DOI: 10.1172/jci135953
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
Funders: Howard Hughes Medical Institute, Bill and Melinda Gates Foundation, Yale University, Gilead Sciences, Johns Hopkins University, National Institutes of Health, Center for AIDS Research, University of Washington, Center for AIDS Research, Johns Hopkins University, National Institute of Allergy and Infectious Diseases, National Center for Advancing Translational Sciences, Los Alamos National Laboratory
Awards: G1044130170, G1359458754, G1393384650, G2483435703, G2598478226, BEAT-HIV: Delaney Collaboratory to Cure HIV-1 Infection by Combination Immunotherapy, G2958655443, G3537001456, G358483467, G378552126, G4573400019, Combined Immunologic Approaches to Cure HIV-1, Cell and Gene Therapy for HIV Cure, G653582874, G7178514535, G720459795, G7241966796, G8753336769, G9000008325, G9000106840, G9000107634, The Johns Hopkins Center for AIDS Research (JHU CFAR), Research Training in Microbial Diseases, G97119092
OpenAlex ID: W3011123312