Journal
OPEN FORUM INFECTIOUS DISEASES
Volume 5, Issue 2, Pages -Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/ofid/ofy032
Keywords
2-LTR circular DNA; activation; drug concentration; sCD27; viral load
Categories
Funding
- European AIDS Treatment Network (NEAT)
- British HIV Association
- CARE and BEAT Martin Delaney Collaboratories of the National Institute of Allergy and Infectious Diseases (NIAID)
- National Institute of Neurological Disorders and Stroke (NINDS)
- National Institute on Drug Abuse (NIDA)
- National Institute of Mental Health (NIMH) of the National Institutes of Health [1UM1AI126619, 1UM1Al126620]
- University of California San Diego Centre for AIDS Research (CFAR) [AI306214]
- Department of Veterans Affairs
- James B. Pendleton Charitable Trust
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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 log 10 copies/mL higher with each log 10 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.
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