| Autor: |
Peluso MJ; Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, and., Bacchetti P; Department of Epidemiology and Biostatistics, UCSF, San Francisco, California, USA., Ritter KD; Accelevir Diagnostics, Baltimore, Maryland, USA., Beg S; Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Lai J; Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Martin JN; Department of Epidemiology and Biostatistics, UCSF, San Francisco, California, USA., Hunt PW; Division of Experimental Medicine, Department of Medicine, UCSF, San Francisco, California, USA., Henrich TJ; Division of Experimental Medicine, Department of Medicine, UCSF, San Francisco, California, USA., Siliciano JD; Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Siliciano RF; Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.; Howard Hughes Medical Institute, Chevy Chase, Maryland, USA., Laird GM; Accelevir Diagnostics, Baltimore, Maryland, USA., Deeks SG; Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, and. |
| Abstrakt: |
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. |
