@article{9794729f99cb471caaac523f70c7e077,
title = "Differential decay of intact and defective proviral DNA in HIV-1–infected individuals on suppressive antiretroviral therapy",
abstract = "BACKGROUND. The relative stabilities of the intact and defective HIV genomes over time during effective antiretroviral therapy (ART) have not been fully characterized. METHODS. We 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. RESULTS. We 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. CONCLUSION. The 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.",
author = "Peluso, {Michael J.} and Peter Bacchetti and Ritter, {Kristen D.} and Subul Beg and Jun Lai and Martin, {Jeffrey N.} and Hunt, {Peter W.} and Henrich, {Timothy J.} and Siliciano, {Janet D.} and Siliciano, {Robert F.} and Laird, {Gregory M.} and Deeks, {Steven G.}",
note = "Funding Information: This work was supported the Delaney AIDS Research Enterprise (DARE; AI096109, A127966). The SCOPE cohort receives support from the UCSF/Gladstone Institute of Virology & Immunology CFAR (P30 AI027763), the CFAR Network of Integrated Systems (R24 AI067039), and the amfAR Institute for HIV Cure Research (amfAR 109301). Additional support was provided by the I4C (UM1 AI126603) and Beat-HIV (UM1 AI126620) Collaboratories, the Howard Hughes Medical Institute, Gilead Sciences (unre- stricted research grant), and the Bill and Melinda Gates Foundation (OPP1115715). MJP receives funding on a training grant NIH/NIAID T32 AI60530-12. Accelevir Diagnostics acknowledges support from SBIR grants from NIH (R44AI124996) and NSF (1738428). Funding Information: Conflict of interest: AccelevirDx is a for-profit company; aspects of the IPDA are the subject of patent application PCT/US16/28822 filed by Johns Hopkins University and AccelevirDx holds an exclusive license for this patent application. MJP, SB, and JL have nothing to disclose. PB, JNM, and SGD report grants from the NIH during the conduct of the study. KDR is an employee of AccelevirDx. PWH reports grants and/or personal fees from Gilead Sciences, Viiv, Janssen, and Biotron, outside the submitted work. TJH reports grants and/or personal fees from Merck & Co. and Gilead Sciences, outside the submitted work. JDS reports personal fees from Gilead Sciences, outside the submitted work. RFS is an inventor on the IPDA patent application. He holds no equity interest in AccelevirDx. GML is an employee of and equity holder in AccelevirDx. SGD reports grants and/ or personal fees from Gilead Sciences, Merck & Co., Viiv, AbbVie, Eli Lilly, ByroLogyx, and Enochian Biosciences outside the submitted work. Funding Information: This work was supported the Delaney AIDS Research Enterprise (DARE; AI096109, A127966). The SCOPE cohort receives support from the UCSF/Gladstone Institute of Virology & Immunology CFAR (P30 AI027763), the CFAR Network of Integrated Systems (R24 AI067039), and the amfAR Institute for HIV Cure Research (amfAR 109301). Additional support was provided by the I4C (UM1 AI126603) and Beat-HIV (UM1 AI126620) Collaboratories, the Howard Hughes Medical Institute, Gilead Sciences (unrestricted research grant), and the Bill and Melinda Gates Foundation (OPP1115715). MJP receives funding on a training grant NIH/NIAID T32 AI60530-12. Accelevir Diagnostics acknowledges support from SBIR grants from NIH (R44AI124996) and NSF (1738428). Publisher Copyright: {\textcopyright} 2020, American Society for Clinical Investigation.",
year = "2020",
month = feb,
day = "27",
doi = "10.1172/jci.insight.132997",
language = "English (US)",
volume = "5",
journal = "JCI insight",
issn = "2379-3708",
publisher = "The American Society for Clinical Investigation",
number = "4",
}