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

Abstract

BackgroundPersistence 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. MethodsResidual 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.ResultsResidual 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. ConclusionsThese 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.

Immune Activation, Inflammation, and Non-AIDS Co-Morbidities in HIV-Infected Patients under Long-Term ART

“…On the other hand, the impact of an early start to therapy on immunological recovery was debated by Amu et al, who showed that the expression of activation (HLA-DR and CD38 on CD4+ T cells) and terminal differentiation (CD127 on CD8+ T cells) markers in T cells were abnormal but comparable between early- and late-treated patients [68]. Similarly, Ruggiero et al demonstrated that there was no difference in levels of soluble and cellular markers of activation measured in patients that started ART at different times after diagnosis [69,70]. These characteristics, alongside early treatment, minimize HIV reservoir size and diversity, prevent the quantitative loss of Th17 cells, and positively impact on local and systemic T cell activation [71,72,73,74,75].…”

Factors associated with high-risk low-level viremia leading to virologic failure: 16-year retrospective study of a Chinese antiretroviral therapy cohort

“…All subjects received first-line ART regimen according to Chinese guidelines for diagnosis and treatment of HIV/AIDS [26]. This included two nucleoside reverse transcriptase inhibitors (NRTIs) and a non-nucleoside reverse transcriptase inhibitor (NNRTI) that are widely used globally [27][28][29][30][31]. All participants were followed up every 3 to 6 months for evaluation of VL, CD4 + T cell counts, and other routine clinical parameters.…”

Association of Viral Persistence and Atherosclerosis in Adults With Treated HIV Infection

“… 21 , 22 Notably, much of the HIV DNA is defective and cannot support the production of replication-competent virions, but it can support the production of viral proteins. 23 , 24 The amount of cell-associated DNA and RNA in blood has been associated with levels of T-cell activation, T-cell proliferation, and soluble markers of inflammation in many 25 , 26 , 27 , 28 , 29 but not all 30 studies.…”