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17 February 2021
HIV Research: Reducing The Reservoir, Preventing Reinfection

HIV-1 is the most common type of Human Immunodeficiency Virus, and remains a major global public health challenge that the COVID-19 pandemic has exacerbated especially in eastern and southern Africa – the epicentre of the HIV epidemic.

In this region there are 800,000 new HIV infections each year, just under half of the global total, according to current research reported on the online research and analysis platform, The Conversation. According to the report, progress towards eliminating AIDS in the region by 2030 was already behind schedule prior to the emergence of COVID-19, and government lockdowns have since slowed down testing, treatment and care.

But there is hope. The University of the Western Cape (UWC) forms part of an international team of researchers from the Institute of Infectious Diseases and Molecular Medicine in the Division of Medical Virology at the University of Cape Town (UCT) and Johns Hopkins University, School of Medicine in Baltimore, USA. 



Their research is entitled Characterizing intact proviral HIV-1 reservoir size and determinants of reservoir dynamics in African populations. According to previous research findings antiretroviral treatment (ART) is unable to clear HIV-1 infection because the virus remains dormant in cells and tissues referred to as the latent reservoir. 

Dr Gordon Harkins, senior lecturer at UWC’s South African National Bioinformatics Institute (SANBI), heads up the research at UWC. 



“HIV attacks immune system cells in the body and uses the cells' machinery to make copies of itself. This reservoir of HIV-infected cells and tissues is established very early after infection in certain immune cells (CD4 T cells). With early treatment the size of the reservoir can be reduced and viral variants that can form at early infection or around the period when ART was started, can be detected in this cellular reservoir,” he explained. 
“If treatment is interrupted, reseeding occurs, which is the process during which the viral numbers can rapidly rebound to attain pre-ART levels. This is why understanding the key factors of latent reservoir establishment, size and dynamics are critical to designing safe and effective eradication strategies.” 



Although much is known about these key areas of interest (reservoir establishment, size and dynamics) in HIV-1 subtype B-infected American men, there remains limited knowledge in the most affected population in the world: subtype C-infected South African women, which represents the current study group. 

“We have three main aims; First we will characterise reservoir size amongst HIV-1 subtypes C-infected women from South Africa and compare this to subtype A and D-infected individuals from Uganda to better understand the barrier to cure in African populations.

“Secondly we will investigate the potential role for viral genetic factors that are drivers of immune evasion and viral replication respectively, in determining reservoir size and composition.

“Thirdly, because it is unknown if different distinct compartments in the body contribute to the latent reservoir in different ways and to what extent the reservoir contributes to viral evolution during viremia by reseeding of infection, we will investigate the temporal dynamics of exchange between the latent reservoir, blood, and cervix compartments that may provide important insights into HIV infection dynamics,” said Dr Harkins.

Dr Harkins is grateful for the funding that will facilitate this research. The total funding awarded from the US National Institutes of Health (NIH) is R13.7 million, of which the UWC sub-award comprises R4.5 million over the next five years  Two UWC masters students, Siphosetu Mazitshana and Nkosazama Nyembezi, have been recruited to conduct this research as part of a larger study investigating reservoir dynamics that will also include measurement of reservoir size, viral promoter function and nef gene function. 

“The latent reservoir represents the single most important barrier to a potential HIV cure,” said Dr Harkins. “The proposed work has potential to make important contributions to HIV reservoir research in sub-Saharan Africa, with the aim of achieving a state of remission even in the absence of antiretroviral treatment.”