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Significant progress has been made in controlling HIV in South Africa, report shows
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Researchers from the South African Medical Research Council (SAMRC) and University of KwaZulu-Natal (UKZN) are inching closer to finding the answer to the natural control of HIV infection, leading to improved health outcomes and quality of life among South Africans.
According to the latest survey by the Human Sciences Research Council, in 2022, there were approximately 7.8 million people afflicted with HIV in South Africa, the highest absolute number of people living with HIV globally.
Yet despite having the largest genetic diversity in the world, African human genome sequences represent the lowest of all the human genomes that have been sequenced worldwide. There is a dire need to leverage genomics to back up and scale targeted intervention programmes to put more people living with HIV on effective treatment.
Of particular interest in the global investigations into HIV is “elite controllers” (ECs), a rare group of HIV‐1‐positive individuals whose immune systems can seemingly suppress the infection from developing without taking antiretrovirals (ARVs).
Elite controller research
For every 200 people living with HIV, around one may be an elite controller (0.5%). In South Africa, with its high rate of HIV infection, the prevalence of ECs also appears to be higher. By “unmasking” the secrets of ECs through research, clues can be revealed, and new therapies potentially developed to benefit broader groups of people living with the disease.
In order to identify the polymorphism and mutations within individuals of African descent, and understand how they are associated with HIV disease progression, Veron Ramsuran, associate professor at UKZN, and Thumbi Ndung'u, director for Basic & Translational Science at the Africa Health Research Institute, joined hands with SAMRC, MGI and local South African clinics in 2019 to take their 20+ years of work in EC research to the next level using whole genome sequencing (WGS).
“The HIV Host Genome project was started at the same time as we launched SAMRC’s African Genomics Centre in Cape Town with the support from MGI,” said project co-investigator Rizwana Mia, also co-founder of the SAMRC Genomics Centre and senior programme manager in Precision Medicine at SAMRC.
“The partnership saw MGI putting down a high-throughput sequencing workflow and assisted us with the specialised scaled infrastructure design in our lab. This was at a time when there was no real infrastructure for large-scale next-generation sequencing in Africa.
“More importantly, by moving our laboratory workflow to scale, we are hoping to develop genomic research to address this quadruple burden of disease that South Africa faces,” explained Mia. “Our project looks at a unique cohort of patients that have the ability to control the HIV virus to ascertain how disease progresses and the host-directed mechanisms for innate immune control.
"In addition, we included family sets to help us better understand the relationship between paediatric non-progressors and their parents who are also HIV positive, to uncover any genetic differences that may contribute to host immune control of HIV.
“We've identified new genes and polymorphism that are playing a role with HIV disease through new data generated from whole genome sequencing,” said Veron Ramsuran, principal investigator of the HIV Host Genome project.
“Traditionally, there is a list of mutations or genes that are known to associate with HIV, yet they are largely based on studies on Caucasian populations. Our HIV research is adding to the general pool of knowledge pertaining to individuals of African descent, which will thereby inform new treatment and new vaccine opportunities.
“What's important is also understanding how drugs interact with the individual,” added Ramsuran. “We’ve found in the past that certain polymorphism is associated with drug metabolism in genes.
"Building on this understanding of drugs in combination with the genetics of the individual, we can develop prediction tools to inform clinicians on drug type or dosage depending on the presence of the polymorphism to facilitate a more rapid metabolism of the drug.”
Genome research expansion
Encouragingly, investigations into Africa’s diseases will continue beyond this point. The HIV Host Genome project has laid the groundwork for the ambitious National 110K Human Genome Project.
This large-scale population study will involve 110,000 participants from the South African population, aiming to understand more about their genomic diversity, address various health challenges, and pave the way for personalised medicine in the country.
Furthermore, the data collected will be incorporated into a national population database, enhancing research outcomes and deepening disease understanding for Africa.
Given South Africa’s diverse population, limited human genomics data and significant healthcare burden from diseases such as HIV, understanding pathogenesis and inherent mutations is important for implementing targeted treatments and public-health programmes.
With its lower sequencing cost, high quality data, and efficient all-in-one workflows, MGI's equipment plays an instrumental role and will continue to drive progress in studying rare HIV phenotypes, which holds great promise in advancing the development of targeted interventions and cures – not only for HIV – but many other diseases.
“Looking at the genetic variation and its impact on HIV is a gamechanger, because it will shed light on some of the best immune responses that can be generated against the HIV virus,” stated Thumbi Ndung'u, principal investigator of several of the project’s cohort studies.
“And actually, this knowledge will be widely applicable and could have an impact on other diseases - infectious and non-infectious – as well as their drug interventions. It will make sure that Africans, just like everybody else, are at the centre of drug- and vaccine development.”
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