Novel Approaches Towards a Functional Cure of HIV/AIDS

Abstract

Therapeutic approaches towards a functional cure or eradication of HIV have gained renewed momentum upon encouraging data emerging from studies in SIV monkey models and recent results from human clinical studies. However, a multitude of questions remain to be addressed, including how to deal with the latent viral reservoir, how to boost the host immune response to the virus and what the hurdles are to reach relevant viral compartments in the body. Advances have been made especially with regard to identifying agents that can reactivate the latent virus in vivo and boost the cellular and humoral immunity, but it remains largely unclear whether any of these strategies can awaken a sufficiently large fraction of the viral reservoir and whether the boosted immunity can prevent rapid viral replication once antiretroviral treatments are stopped. Key PointsHIV cure remains a scientific challenge to this day.Viral control without antiretroviral treatment is the main goal of a functional cure for HIV. Combination approaches may be needed for successful virus control.

In Situ Characterization of Human Lymphoid Tissue Immune Cells by Multispectral Confocal Imaging and Quantitative Image Analysis; Implications for HIV Reservoir Characterization

“…HIV infection is a chronic infection that persists in lymphoid tissues even in the context of antiretroviral therapy causing profound tissue-specific alterations (15,55,(78)(79)(80). This characteristic of HIV pathogenesis has prompted several cure strategies aiming at viral reservoir elimination to be developed over the past years (81). In this context, we designed a panel that leverages the analytical strength of the RNAscope in situ hybridization platform (ACD) and resolving power of confocal microscopy for topological examination and quantification of HIV-specific RNA in tissues.…”

In the Era of mRNA Vaccines, Is There Any Hope for HIV Functional Cure?

“…Therefore, even in the hypothetical case that the most optimized therapeutic vaccine is obtained, this will probably not be enough to eliminate the reservoir. Co-administration of a therapeutic mRNA vaccine with drugs that could reactivate the reservoir of HIV (Kick-and-Kill strategy), immune checkpoint inhibitors, or broadly neutralizing antibodies are all promising approaches [ 92 ]. Maybe the functional cure of HIV is in one of those combined treatments, but first, every single strategy will need to be optimized separately to make a combination successful.…”

“…As it is now clear that a vaccine alone would not be enough to cure HIV, attention has turned into combining vaccines with other treatments, attacking the virus from multiple sides [ 91 , 92 ]. A strategy that has received much attention in recent years is the combination of therapeutic vaccines with latency reversal agents (LRA) and blocking antibodies.…”

Hydrogen sulfide blocks HIV rebound by maintaining mitochondrial bioenergetics and redox homeostasis

“…One of the aims of the HIV-1 functional cure is to identify small molecules that can be combined with ART to delay or halt virus replication, reactivation, and replenishment of the latent reservoir (59,60). Having shown that diminished levels of endogenous H2S is associated with HIV-1 reactivation, we next examined if elevating H2S levels using a small-molecule H2S donor-GYY4137 sustains HIV-1 latency.…”