Comparison of the Biological Basis for Non-HIV Transmission to HIV-Exposed Seronegative Individuals, Disease Non-Progression in HIV Long-Term Non-Progressors and Elite Controllers

Abstract

HIV-exposed seronegative individuals (HESIs) are a small fraction of persons who are multiply exposed to human immunodeficiency virus (HIV), but do not exhibit serological or clinical evidence of HIV infection. In other words, they are groups of people maintaining an uninfected status for a long time, even after being exposed to HIV several times. The long-term non-progressors (LTNPs), on the other hand, are a group of HIV-infected individuals (approx. 5%) who remain clinically and immunologically stable for an extended number of years without combination antiretroviral therapy (cART). Meanwhile, elite controllers are comprise a much lower number (0.5%) of HIV-infected persons who spontaneously and durably control viremia to below levels of detection for at least 12 months, even when using the most sensitive assays, such as polymerase chain reaction (PCR) in the absence of cART. Despite the fact that there is no universal agreement regarding the mechanisms by which these groups of individuals are able to control HIV infection and/or disease progression, there is a general consensus that the mechanisms of protection are multifaceted and include genetic, immunological as well as viral factors. In this review, we analyze and compare the biological factors responsible for the control of HIV in these unique groups of individuals.

New Insights into HIV Life Cycle, Th1/Th2 Shift during HIV Infection and Preferential Virus Infection of Th2 Cells: Implications of Early HIV Treatment Initiation and Care

“…Consequently, long-term non-progressor phenotypes are more commonly observed in HIV-2 infection. HIV-1 is more infective and highly transmissible than HIV-2, and it is more pathogenic and establishes higher virus loads during the asymptomatic phase of infection, referred to as clinical latency, resulting in faster disease progression [7]. HIV-1 encodes a vpu gene (unlike HIV-2, which encodes the vpx gene) that is vital during HIV-1 virion release from the infected cell surface during egress.…”

Genotypic and Phenotypic Characterization of Replication-Competent HIV-2 Isolated from Controllers and Progressors

“…Individuals who control HIV-1 infection without treatment are rare [4]. They are typically split into different groups, including aviremic elite controllers (ECs) who have no or little detectable viral RNA in their plasma and no CD4+ loss, viremic long-term non-progressors (LTNPs) with detectable viral loads but no CD4+ loss, and post-treatment controllers [5,6]. The precise mechanisms underlying the control of HIV-1 remain unclear [6].…”

“…They are typically split into different groups, including aviremic elite controllers (ECs) who have no or little detectable viral RNA in their plasma and no CD4+ loss, viremic long-term non-progressors (LTNPs) with detectable viral loads but no CD4+ loss, and post-treatment controllers [5,6]. The precise mechanisms underlying the control of HIV-1 remain unclear [6]. However, host factors, specific CD4+ and CD8+ T cell immune responses, and specific HLA class I alleles are known to play significant roles [7][8][9].…”

“…However, host factors, specific CD4+ and CD8+ T cell immune responses, and specific HLA class I alleles are known to play significant roles [7][8][9]. Additionally, intrinsic viral characteristics can also contribute to virologic control, including deletion in the long-terminal repeat and Nef [10,11], envelope sequences [12,13], low viral fitness [14], and the nature of integration sites [10][11][12]15] (reviewed in [6]). Gaining a deeper understanding of the mechanisms governing HIV control could potentially provide valuable insights into interventions aimed at enabling viral control in all people with HIV without the need for antiretroviral therapy.…”