Differential decay of intact and defective proviral DNA in HIV-1–infected individuals on suppressive antiretroviral therapy
Year: 2020
Type: article
Study design: Observational Study
Abstract: BACKGROUNDThe relative stabilities of the intact and defective HIV genomes over time during effective antiretroviral therapy (ART) have not been fully characterized.METHODSWe used the intact proviral DNA assay (IPDA) to estimate the rate of change of intact and defective proviruses in HIV-infected adults on ART. We used linear spline models with a knot at seven years and a random intercept and slope up to the knot. We estimated the influence of covariates on rates of change.RESULTSWe studied 81 individuals for a median of 7.3 (IQR 5.9-9.6) years. Intact genomes declined more rapidly from initial suppression through seven years (15.7% per year decline; 95% CI -22.8%, -8.0%) and more slowly after seven years (3.6% per year; 95% CI -8.1%, +1.1%). The estimated half-life of the reservoir was 4.0 years (95% CI 2.7-8.3) until year seven and 18.7 years (95% CI 8.2-infinite) thereafter. There was substantial variability between individuals in the rate of decline until year seven. Intact provirus declined more rapidly than defective provirus (P < 0.001) and showed a faster decline in individuals with higher CD4+ T cell nadirs.CONCLUSIONThe biology of the replication-competent (intact) reservoir differs from that of the replication-incompetent (non-intact) pool of proviruses. The IPDA will likely be informative when investigating the impact of interventions targeting the reservoir.FUNDINGDelaney AIDS Research Enterprise, UCSF/Gladstone Institute of Virology & Immunology CFAR, CFAR Network of Integrated Systems, amfAR Institute for HIV Cure Research, I4C and Beat-HIV Collaboratories, Howard Hughes Medical Institute, Gilead Sciences, Bill and Melinda Gates Foundation.
Source: JCI Insight
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,100
Funders: National Science Foundation, Howard Hughes Medical Institute, Bill and Melinda Gates Foundation, amfAR, The Foundation for AIDS Research, Gilead Sciences, Delaney AIDS Research Enterprise, National Institutes of Health, University of California, San Francisco, National Institute of Mental Health, National Institute of Allergy and Infectious Diseases
Awards: G1066646890, G1393384650, G1531094742, G1826974679, G1869768155, G2428225874, BEAT-HIV: Delaney Collaboratory to Cure HIV-1 Infection by Combination Immunotherapy, G3181090803, DARE: Delaney AIDS Research Enterprise to find a cure., G4250923135, G432530805, G4573400019, Combined Immunologic Approaches to Cure HIV-1, SBIR Phase II: Development and Optimization of a New Molecular Test to quantify Latent HIV-1 in Samples from HIV-1 Infected Individuals., Centralized Resource to Accurately Quantify Latent and Expressed HIV Reservoirs, G6121969458, G6444951560, G6759634997, G682474142, G6919811502, G864826021, G9000052507, CFAR Network of Integrated Clinical Systems (CNICS), G97119092
OpenAlex ID: W3005734087