Learning from Persistent Viremia: Mechanisms and Implications for Clinical Care and HIV-1 Cure
Date:
11/13/2023
Topics:
Citation:
Wu F, Simonetti FR. Learning from Persistent Viremia: Mechanisms and Implications for Clinical Care and HIV-1 Cure. Curr HIV/AIDS Rep. 2023 Nov 13. doi: 10.1007/s11904-023-00674-w. Epub ahead of print. PMID: 37955826.
Abstract
Purpose of Review: In this review, we discuss what persistent viremia has taught us about the biology of the HIV-1 reservoir during antiretroviral therapy (ART). We will also discuss the implications of this phenomenon for HIV-1 cure research and its clinical management.
Recent Findings: While residual viremia (RV, 1–3 HIV-1 RNA copies/ml) can be detected in most of people on ART, some individuals experience non-suppressible viremia (NSV, > 20–50 copies/mL) despite optimal adherence. When issues of drug resistance and pharmacokinetics are ruled out, this persistent virus in plasma is the reflection of virus production from clonally expanded CD4+ T cells carrying proviruses. Recent work has shown that a fraction of the proviruses source of NSV are not infectious, due to defects in the 5′-Leader sequence. However, additional viruses and host determinants of NSV are not fully understood.
Summary: The study of NSV is of prime importance because it represents a challenge for the clinical care of people on ART, and it sheds light on virus-host interactions that could advance HIV-1 remission research.
Recent Findings: While residual viremia (RV, 1–3 HIV-1 RNA copies/ml) can be detected in most of people on ART, some individuals experience non-suppressible viremia (NSV, > 20–50 copies/mL) despite optimal adherence. When issues of drug resistance and pharmacokinetics are ruled out, this persistent virus in plasma is the reflection of virus production from clonally expanded CD4+ T cells carrying proviruses. Recent work has shown that a fraction of the proviruses source of NSV are not infectious, due to defects in the 5′-Leader sequence. However, additional viruses and host determinants of NSV are not fully understood.
Summary: The study of NSV is of prime importance because it represents a challenge for the clinical care of people on ART, and it sheds light on virus-host interactions that could advance HIV-1 remission research.