HIV cure strategies: which ones are appropriate for Africa?

Abstract

Although combination antiretroviral therapy (ART) has reduced mortality and improved lifespan for people living with HIV, it does not provide a cure. Patients must be on ART for the rest of their lives and contend with side effects, unsustainable costs, and the development of drug resistance. A cure for HIV is, therefore, warranted to avoid the limitations of the current therapy and restore full health. However, this cure is difficult to find due to the persistence of latently infected HIV cellular reservoirs during suppressive ART. Approaches to HIV cure being investigated include boosting the host immune system, genetic approaches to disable co-receptors and the viral genome, purging cells harboring latent HIV with latency-reversing latency agents (LRAs) (shock and kill), intensifying ART as a cure, preventing replication of latent proviruses (block and lock) and boosting T cell turnover to reduce HIV-1 reservoirs (rinse and replace). Since most people living with HIV are in Africa, methods being developed for a cure must be amenable to clinical trials and deployment on the continent. This review discusses the current approaches to HIV cure and comments on their appropriateness for Africa.

HIV cure: an acceptability scientific agenda

“…The first, termed ‘eradication cure’ or ‘sterilizing cure’ involves complete eradication of all replication-competent provirus from the infected person, including removal of viruses in cellular and anatomical reservoirs [ 2 , 3 ▪ , 10 , 25 , 26 ]. The second form is termed ‘functional cure’ or long-term remission whereby the viral reservoir is depleted to the extent that cessation of ART will not result in immediate viral rebound [ 2 , 3 ▪ , 10 , 25 , 26 ]. The gold standard of infectious disease cure is elimination of the pathogen; therefore, everyone will take eradication cure as the ideal.…”

“…Therefore, it is not clear what people living in Africa want from an HIV cure. Some of the strategies such as gene therapy, for example modification of T cell ex vivo and reinfusion into the patient, and some types of immunotherapy such as chimeric antigen receptor may not be feasible in Africa [ 2 ]. Although patients everywhere may be hesitant to undergo ATI, PLWH in Africa may have a lot more hesitation for unclear reasons [ 3 ▪ ].…”

“…Although antiretroviral therapy (ART) has been revolutionary in transforming HIV from a death sentence to a manageable chronic disease, it does not provide cure [ 1 , 2 , 3 ▪ , 4 , 5 , 6 ▪▪ , 7 ]. Patients must commit to lifelong medications and deal with issues such as incomplete viral suppression, social stigma, drug resistance, medication side effects and unsustainable costs.…”

High-resolution Inference of Multiplexed Anti-HIV Gene Editing using Single-Cell Targeted DNA Sequencing

“…2,3 As access to lifelong ART is extremely challenging in resourcelimited settings where HIV predominates, there is a desperate need for effective prophylactic and curative strategies. 4,5 Several HIV cure strategies are currently in development, including "shock-and-kill", 6 "block-andlock" 7 , and oncology-derived immunomodulatory 8 and bone marrow transplantation approaches targeting the latent HIV reservoir. [9][10][11] The discovery of the CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-Cas9 gene editing system has raised new hopes for gene therapy-based HIV cure strategies.…”

Retinoic Acid Boosts HIV-1 Replication in MacrophagesviaCCR5/SAMHD1-Dependent and mTOR-Modulated Mechanisms

“…Recent studies on autopsy tissues from ART-treated PLWH documented the presence of intact VRs in the majority of tissues investigated [6][7][8] . The persistence of VRs is well-documented in long-lived memory CD4 + T cells and multiple investigation efforts were made to purge VRs in this cellular compartment 3,9 . In addition, other immune cells such as macrophages residing in deep tissues may represent sanctuaries for VRs during ART, but remain poorly investigated due to restricted biological sample accessibility [10][11][12][13][14][15][16][17] .…”