The Role of Elite Controllers and Post-Treatment Controllers in Advancing HIV Cure Research

As of 2022, 39.0 million people were recorded to be living with HIV, with an estimated mortality of 40.4 million lives. Among people living with HIV, a minority demonstrate extraordinary control over viral replication without the need for antiretroviral therapy (ART), called elite controllers (ECs). Other individuals affected by HIV, known as post-treatment controllers (PTCs), maintain viral suppression after discontinuation of ART. This thesis analyses recent findings from relevant research papers in the field to explore the mechanisms that confer elite control and post-treatment control, as well as the implications for HIV cure research. Elite controllers demonstrate various immune mechanisms for viral control, including CD8+T cells targeting conserved HIV epitopes, HLA molecules facilitating effective immune recognition, and proviral integration in pseudogenic regions reducing viral transcription. Additionally, ECs exhibit characteristics such as preserved CD4+ T cell functionality and enhanced anti-HIV immune responses through factors like suppression of miR10a-5p and elevated α-ketoglutaric acid. Post-treatment controllers demonstrate distinct immune responses, restraining viral reservoir expansion and replication post-ART interruption. Mechanisms that confer post-treatment control are associated with limiting reservoir size, controlling CD4+ T cell activation, and activating NK cells to reduce viral replication. These controllers play a crucial role in advancing HIV cure research. This thesis discusses recent findings in the field, exploring novel strategies such as tHIVConsvX immunogen, anti-PD-1 antibodies to enhance CD8+ T cell functionality, miRNA inhibition to boost cytotoxic responses, and early ART administration to minimize viral reservoir size. Additionally, strategies like ART combined with immunotoxin treatment, Shock-and-kill approaches employing Latency Reversing Agents (LRAs), and Block-and- Lock strategies utilizing TAT inhibitors for deep latency induction are discussed. Moreover, probiotic supplementation emerges as a possible therapy for HIV, demonstrating positive effects on CD4+ T cell counts, disease manifestations, and inflammatory markers. By evaluating the mechanisms conferring elite and post-treatment control, this thesis sheds light on functional cures for HIV.