Factors Associated With Persistence of Plasma HIV-1 RNA During Long-term Continuously Suppressive Firstline Antiretroviral Therapy

Ruggiero, Alessandra, Cozzi-Lepri, Alessandro, Beloukas, Apostolos ORCID: 0000-0001-5639-0528, Richman, Douglas, Khoo, Saye ORCID: 0000-0002-2769-0967, Phillips, Andrew and Geretti, Anna Maria ORCID: 0000-0002-3670-6588 (2018) Factors Associated With Persistence of Plasma HIV-1 RNA During Long-term Continuously Suppressive Firstline Antiretroviral Therapy. OPEN FORUM INFECTIOUS DISEASES, 5 (2). ofy032-.

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Official URL: http://dx.doi.org/10.1093/ofid/ofy032

Abstract

<h4>Background</h4>Persistence of plasma HIV-1 RNA during seemingly effective antiretroviral thereapy (ART) is incompletely understood. Using an ultrasensitive assay, this cross-sectional study investigated residual plasma HIV-1 RNA in subjects maintained on firstline ART with continuous viral load suppression <50 copies/mL for ≤15 years without recognized viral load blips or treatment interruptions and explored its relationship with the duration of suppressive ART, efavirenz concentrations in plasma, 2-LTR circular HIV-1 DNA (2-LTRc DNA) in peripheral blood mononuclear cells, and cellular (CD4 plus CD26/CD38/CD69; CD8 plus CD38/HLA-DR/DP/DQ) and soluble (sCD14, sCD27, sCD30, IL-6) markers of immune activation in peripheral blood.<h4>Methods</h4>Residual plasma HIV-1 RNA, total HIV-1 DNA and 2-LTRc DNA were quantified by real-time and digital droplet PCR. Cellular (CD4 plus CD26/CD38/CD69; CD8 plus CD38/HLA-DR/DP/DQ) and soluble (sCD14, sCD27, sCD30, IL-6) markers of immune activation were measured by flow cytometry and ELISA.<h4>Results</h4>Residual plasma HIV-1 RNA and 2-LTRc DNA were detected in 52/104 (50%) and 24/104 (23%) subjects, respectively. Among subjects with detectable HIV-1 RNA, 50/52 showed levels ≤11 copies/mL. In adjusted analyses, HIV-1 RNA levels were 0.37 log<sub>10</sub> copies/mL higher with each log<sub>10</sub> U/mL increase in sCD27 (95% confidence interval, 0.01-0.73; <i>P</i> = .02). No significant association was found between residual plasma HIV-1 RNA and other explored parameters.<h4>Conclusions</h4>These findings point to an ongoing relationship between plasma HIV-1 RNA and selected markers of immune activation during continuously suppressive ART. The novel direct association with levels of sCD27 warrants further investigation.

Item Type:	Article
Uncontrolled Keywords:	2-LTR circular DNA, activation, drug concentration, sCD27, viral load
Depositing User:	Symplectic Admin
Date Deposited:	09 Mar 2018 11:09
Last Modified:	19 Jan 2023 06:38
DOI:	10.1093/ofid/ofy032
Open Access URL:	https://academic.oup.com/ofid/article-lookup/doi/1...
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3018787