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Review
. 2021 Aug 3;18(1):21.
doi: 10.1186/s12977-021-00565-1.

Addressing an HIV cure in LMIC

Sherazaan D Ismail #  1 , Joshua Pankrac #  2 , Emmanuel Ndashimye  2   3 , Jessica L Prodger  2   4   5 , Melissa-Rose Abrahams  1 , Jamie F S Mann  2   6 , Andrew D Redd  1   5   7 , Eric J Arts  8   9
Affiliations
Review

Addressing an HIV cure in LMIC

Sherazaan D Ismail et al. Retrovirology. .

Abstract

HIV-1 persists in infected individuals despite years of antiretroviral therapy (ART), due to the formation of a stable and long-lived latent viral reservoir. Early ART can reduce the latent reservoir and is associated with post-treatment control in people living with HIV (PLWH). However, even in post-treatment controllers, ART cessation after a period of time inevitably results in rebound of plasma viraemia, thus lifelong treatment for viral suppression is indicated. Due to the difficulties of sustained life-long treatment in the millions of PLWH worldwide, a cure is undeniably necessary. This requires an in-depth understanding of reservoir formation and dynamics. Differences exist in treatment guidelines and accessibility to treatment as well as social stigma between low- and-middle income countries (LMICs) and high-income countries. In addition, demographic differences exist in PLWH from different geographical regions such as infecting viral subtype and host genetics, which can contribute to differences in the viral reservoir between different populations. Here, we review topics relevant to HIV-1 cure research in LMICs, with a focus on sub-Saharan Africa, the region of the world bearing the greatest burden of HIV-1. We present a summary of ART in LMICs, highlighting challenges that may be experienced in implementing a HIV-1 cure therapeutic. Furthermore, we discuss current research on the HIV-1 latent reservoir in different populations, highlighting research in LMIC and gaps in the research that may facilitate a global cure. Finally, we discuss current experimental cure strategies in the context of their potential application in LMICs.

Keywords: Cure; HIV-1; LMICs; Low-and-middle income countries; Reservoir.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
ART regimen chosen for first-line therapy can affect eligibility for a therapeutic cure. The incidence of treatment failure and/or drug resistance on an NNRTI+2 NRTI regimen is greatly increased relative to individuals receiving DTG+2 NRTI treatment. As a result of failing first-line therapy, PLWH may initiate PI- and RAL-based regimens, which have heightened incidence of failure and resistance. Effective ART allows more PLWH to maintain first-line therapy and facilitates initiatives to achieve therapeutic cure. NNRTI non-nucleoside reverse transcriptase inhibitor, NRTI nucleoside reverse-transcriptase inhibitor, DTG dolutregravir, PI protease inhibitor, RAL raltegravir
Fig. 2
Fig. 2
Faster subtype D versus subtype A HIV-1 treatment failure observed over first- and second-line treatments. The Joint Clinical Research Centre in Kampala, Uganda follows approximately 12,000 HIV-infected patients treated with antiretroviral drugs. Resistance testing is performed in cases of treatment failure—VL > 1000 copies/ml or two CD4 cell counts < 200/ml. ~ 95% of all patients on first-line treatment maintain undetectable VL in Uganda. < 50% reach and maintain undetectable VL on salvage therapy. As part of standard of care, we subtype (C) and analyze drug resistance genotypes of all patients failing treatment (D) on first-line (E) or “salvage” therapy (F)
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