Abstract

HIV-infected individuals who maintain control of virus without antiretroviral therapy (ART) are called HIV controllers. The immune responses of these individuals suppress HIV viral replication to low levels or, in the case of elite controllers, to undetectable levels. Although some research indicates a role for inferior virulence of the infecting viral strain in natural control, perhaps by way of defective Nef protein function, we find that the majority of research in HIV controllers highlights CD8 T cells as the main suppressor of viral replication. The most convincing evidence for this argument lies in the strong correlation between certain HLA-I alleles, especially B*57, and HIV control status, a finding that has been replicated by many groups. However, natural control can also occur in individuals lacking these specific HLA alleles, and our understanding of what constitutes an effective CD8 T-cell response remains an incomplete picture. Recent research has broadened our understanding of natural HIV control by illustrating the interactions between different immune cells, including innate immune effectors and antigen-presenting cells. For many years, the immune responses of the natural HIV controllers have been studied for clues on how to achieve functional cure in the rest of the HIV-infected population. The goal of a future functional cure to HIV is one where HIV-infected individuals’ immune responses are able to suppress virus long-term without requiring ART. This review highlights recent advances in our understanding of how HIV controllers’ natural immune responses are able to suppress virus.

Highlights

  • This review aims to summarize the field’s current understanding of natural HIV controllers, with a focus on recent advances examining the CD8 T-cell response in these individuals and harnessing this knowledge for future therapies

  • We will assume the following definitions and specify any deviations: HIV controllers maintain viral loads of less than 2,000 RNA copies per milliliter of plasma off-antiretroviral therapy (ART). This group of HIV controllers can be further divided into elite controllers, individuals who maintain undetectable viremia (HIV RNA

  • Some studies focus on long-term non-progressors (LTNPs), who are HIVinfected individuals who remain asymptomatic for a prolonged period time off-ART with CD4 cell counts higher than 500, and do not restrict based on viral load

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Summary

Invited Reviewers

F1000 Faculty Reviews are written by members of the prestigious F1000 Faculty. They are commissioned and are peer reviewed before publication to ensure that the final, published version is comprehensive and accessible. The reviewers who approved the final version are listed with their names and affiliations. Any comments on the article can be found at the end of the article

Introduction
Number Percent Number Percent Number
Characteristics Associated with the Clinical Nonprogressor Phenotype Are
Elite Controllers Reduce HIV Replication In Vitro and Modulate HIV Restriction
Among HIV Elite Controllers and Persons With Medically Controlled HIV
Findings
Node Inflammation With Distinct Inflammatory Pathways in Human

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