Cumulative Antiretroviral Exposure Measured in Hair Is Not Associated With Measures of HIV Persistence or Inflammation Among Individuals on Suppressive ART

Abstract

Data on the relationship of antiretroviral exposure to measures of human immunodeficiency virus (HIV) persistence are limited. To address this gap, multiple viral, immunologic, and pharmacologic measures were analyzed from individuals with sustained virologic suppression on therapy (median 7 years) in the AIDS Clinical Trials Group A5321 cohort. Among 110 participants on tenofovir-(TFV)-disoproxil-fumarate (TDF)/emtricitabine (FTC)-containing regimens, we found no significant correlation between hair concentrations of individual antiretrovirals (ARVs) in the regimen and measures of HIV persistence (plasma HIV-1 RNA by single copy assay, cell-associated-DNA, cell-associated RNA) or soluble markers of inflammation. These findings suggest that higher systemic ARV exposure may not impact HIV persistence or inflammation.

Incomplete ART adherence is associated with higher inflammation in individuals who achieved virologic suppression in the START study

“…In addition, these studies were conducted in diverse observational and research cohorts vastly representative of real‐world clinical populations. This is in comparison to recent studies in participants who had very long‐standing and sustained viral suppression, where cumulative drug exposure was not associated with biomarkers of inflammation .…”

“…In addition, these studies were conducted in diverse observational and research cohorts vastly representative of real-world clinical populations. This is in comparison to recent studies in participants who had very long-standing and sustained viral suppression, where cumulative drug exposure was not associated with biomarkers of inflammation [35]. While treated HIV infection has been associated with persistent elevations of IL-6 and CRP in multiple cohorts and clinical trials [5,26,36], the role of SAA in this setting remains poorly understood.…”

Two‐drug vs. three‐drug combinations for HIV‐1: Do we have enough data to make the switch?

“…These data are compatible with the hypothesis that reducing the pression on viral replication might favour inflammation and monocyte activation even in the absence of virological failure. In contrast to this notion, a previously mentioned study did not find any correlation between hair concentration of antiretrovirals, a cumulative measure of drug exposure, and plasma levels of CRP, IL‐6, soluble CD14, soluble CD163, TNF α , or interferon gamma‐induced protein .…”

“…In contrast, Gandhi et al . looked at cumulative antiretroviral exposure in hair in 110 PLWH on tenofovir‐disoproxil fumarate/emtricitabine containing regimens and found it was not associated with measures of HIV persistence or inflammation. They concluded that this lack of correlation suggests that increasing exposure to currently available ART would not have a significant impact on HIV‐1 persistence or inflammation.…”

A Simpler and More Sensitive Single-Copy HIV-1 RNA Assay for Quantification of Persistent HIV-1 Viremia in Individuals on Suppressive Antiretroviral Therapy

“…RCAS internal control for viral RNA recovery. For this and previous studies, a known quantity of replication-competent avian leukosis virus (ALV) long terminal repeat (LTR) with a splice adaptor (RCAS) (12,15,(17)(18)(19) virions (1.2 ϫ 10 6 ) was spiked into each plasma sample and measured as an internal control for viral RNA recovery and amplification. The RCAS internal control was obtained from the HIV Dynamics and Replication Program (HIV DRP) at the National Cancer Institute courtesy of Stephen H. Hughes (https://home.ncifcrf.gov/hivdrp/rcas/contact.html).…”