Factors Associated With Persistence of Plasma HIV-1 RNA During Long-term Continuously Suppressive Firstline Antiretroviral Therapy. (3rd February 2018)

• Record Type: Journal Article
• Authors: Ruggiero, Alessandra; Cozzi-Lepri, Alessandro; Beloukas, Apostolos; Richman, Douglas; Khoo, Saye; Phillips, Andrew; Geretti, Anna Maria
• Is Part Of: Open forum infectious diseases. Volume 5:Number 2(2018)
• Publication Date: 2018-02-03
• Subjects: 2-LTR circular DNA -- activation -- drug concentration -- sCD27 -- viral load; Communicable diseases -- Periodicals; Medical microbiology -- Periodicals; Infection -- Periodicals; 616.9
• DOI: 10.1093/ofid/ofy032
• Languages: English
• ISSNs: 2328-8957

Abstract

Abstract: Background: 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. Methods: 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. Results: 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 log10 copies/mL higher with each log10 U/mL increase in sCD27 (95% confidence interval, 0.01–0.73; P = .02). No significant association was found between residual plasma HIV-1 RNA and other explored parameters. Conclusions: 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.