Mechanism of Viral Suppression among HIV Elite Controllers and Long-Term Nonprogressors in Nigeria and South Africa

Abstract

A subgroup among people living with HIV (PLHIV) experience viral suppression, sometimes to an undetectable level in the blood and/or are able to maintain a healthy CD4+ T-cell count without the influence of antiretroviral (ARV) therapy. One out of three hundred PLHIV fall into this category, and a large sample of this group can be found in areas with a high prevalence of HIV infection such as Nigeria and South Africa. Understanding the mechanism underpinning the nonprogressive phenotype in this subgroup may provide insights into the control of the global HIV epidemic. This work provides mechanisms of the elite control and nonprogressive phenotype among PLHIV in Nigeria and South Africa and identifies research gaps that will contribute to a better understanding on HIV controllers among PLHIV.

Keywords: HIV elite controllers; Nigeria; South Africa; long-term nonprogressors; viraemic controllers.

Figure 1

Understanding the mechanism of viral suppression and favorable disease outcomes among HIV elite controllers and other HIV controllers. (A) Without the influence of barriers, such as antiretroviral drugs, or unique features that contribute to viral suppression among the elite controllers, viraemic controllers, or long-term nonprogressors, HIV replicates successfully and infects new CD4⁺ T cells. This eventually causes a high viral load in the host system. (B) In HIV controllers, such as elite controllers and viraemic controllers, one or more of the stages of HIV’s life cycle is inhibited or interrupted by (i) host unique features such as potent immune responses that are capable of effectively neutralizing, engulfing, or lysing HIV-infected cells; favorable genetic variants that do not support HIV replication; viral restriction factors that are host-acting proteins that provide first-line protection against infection of new host cells; (ii) viral factor, specifically, deleterious mutations in the HIV genome that may cause loss of fitness during viral replication. The mechanism of the nonprogressive phenotype in HIV infection can therefore be explicitly delineated when specific features that favor positive disease outcomes among the HIV controllers are identified.