Could early treatment with antiretroviral (ARV) therapy help the body fight off HIV? Researchers affiliated with the Sub-Saharan African Network for TB/HIV Research Excellence (SANTHE) are convinced that early ARV therapy is critical to the treatment of HIV.

 

Researchers at the University of KwaZulu-Natal (UKZN) in Durban, South Africa are conducting studies they believe show
promise for a more effective treatment and possible prevention or elimination of HIV at a lower cost.

 

Control, elimination and eradication are the three strategies for disease prevention and control.

 

In research currently going on at the HIV Pathogenesis Programme (HPP) at UKZN, the SANTHE researchers are investigating whether ARV treatment started within days of exposure to HIV could rid the body of the virus. This works with the same principle of prophylaxis following incidental or accidental exposure to the HIV.

 

SANTHE is a network of multidisciplinary experts in several universities on the continent empowering African scientists
in pioneering basic, clinical and translational research to inform vaccine development and HIV prevention, treatment and cure strategies.

 

Focusing on the epicenter of the epidemic, South Africa, where 7.1 million people are living with HIV, SANTHE is collaborating with leading academic institutions, non-profits and community groups worldwide on translational research, efficacy studies in animal models and community perspectives of HIV.

 

The consortium of researchers from universities in Botswana, Kenya, Rwanda, South Africa and Zambia, is one of the 11 awardees
of the US$100 million DELTAS Africa program supporting the Africa-led development of world-class researchers and scientific leaders in Africa.

 

The program is being being implemented by The African Academy of Sciences (The AAS) through its programmatic platform, the Alliance for Accelerating Excellence in Science in Africa (AESA), with the support of Wellcome Trust and the UK Department for International Development (DfID).

 

“In one of the studies, we are trying to come up with a strategy for people to live without ARVs after treatment and to ensure HIV does not become a progressive infection. In the research we are conducting, we are treating young women in South Africa with ARVs once they are exposed to the risk. The participants in the study are tested twice a week, so we can immediately detect if they are infected. These individuals might be easier to cure,” says Thumbi Ndung’u, SANTHE program leader and HPP scientific director.

 

SANTHE is collaborating in the study with Females Rising through Education Support and Health (FRESH), a community-based program that has since 2012 reached out to young women at risk from HIV based in Durban, South Africa. Findings from the study will have a major impact on HIV cure strategies and will help African governments and health officials plan for interventions, drawing on lessons from cutting-edge research in the country with the biggest HIV epidemic in the world.

 

SANTHE, through the HIV Pathogenesis Programme at UKZN, is working in partnership with the Ragon Institute, a collaboration of Massachusetts General Hospital, Massachusetts Institute of
Technology and Harvard University.

 

The basic research science on biological samples from FRESH participants and performed at HPP under Ndung’u’s leadership
is based on statistics indicating that young women are very high risk and bear the disproportionate burden of the HIV epidemic. Over two-thirds of 24-year-old women in South Africa are infected with HIV.

 

The program enrolls local women who are HIV negative. Their blood samples are frequently tested (every two weeks) at HPP to see if anyone has recently contracted the virus. If they have, they are started on ARV therapy, and, in turn, provide further samples for the study. Most of the young women in FRESH are disadvantaged and a lot of them are out of school, but through the program they can get economic opportunities, or even go back to school.

 

There are some interesting preliminary findings from the study. For example, HIV usually depletes a person’s CD4 cells – but not so in these women, if they are treated early. The team is exploring whether this has long-term benefits.

 

Ndung’u’s colleague, Krista Dong, who leads the FRESH study, is collaborating with the SANTHE scientists on a two-pronged prevention strategy clinical trial – enrolling the highest risk group at the epicenter of the HIV epidemic and treating early to provide an opportunity to conduct pure research.

 

“Thumbi Ndung’u and our teams at HPP and FRESH will be implementing a clinical trial focused on ‘cure’ or ‘post-treatment control’, enrolling young women whose HIV infection was detected during their enrollment in the FRESH study,” says Dong adding:  “This is a novel treatment that will be given to HIV-infected individuals, that involves a combination of two or three broadly neutralizing antibodies (‘BNAbs’ pronounced bee’-nabs), plus an immunomodulatory agent.”

 

A FRESH Cohort HIV study has discovered that Black women in South Africa have a different composition of bacteria – a
diverse bacteria-microbiome in their vaginal tract – that makes them more vulnerable to HIV infection. Data from the study reveal that most of the women use the injectable hormonal contraceptive, which puts them at a higher risk of HIV infection.

 

The research seeks to understand those
factors (the bacterial conditions that put the women at a higher risk of infection) in the clinical trial that will launch a novel product to alter the composition of the bacteria in the vaginal tract.

 

It seeks to know how the immune system fails to protect women infected via the membranes at the site in the female genital tract where they are first exposed. “The idea of using immunotherapy,
for example chemicals (monoclonal antibodies), is to kill HIV in those infected with HIV and also stimulate a new immune response, to have the body generate, make cells that can fight the infection. We don’t know whether this will work, but we feel there is a possibility,” states Ndung’u.

 

With the first marker for infection, immediate treatment will lead to reducing the virus and blunting the peak-time; the most likely cure strategy, Dong explains. The cure study will begin in 2020 following the 2019 Lactin V new investigation product the researchers have developed to alter the bacteria in the vaginal tract.

 

Since the young women in the FRESH Cohort Acute HIV study are tested so frequently, HIV infection is picked up within days of exposure and they are started on “immediate” treatment.

 

This means that the ARVs stop viral replication very early, before the levels get very high in the blood and before they establish large repositories or “reservoirs” of virus
that cannot be eliminated by drugs alone.

 

Because ARV treatment is started very early and limits the size of the viral reservoir, this may present one of the best opportunities to use a novel treatment to eradicate the virus from the body or to help the body to control the virus without drugs (post-treatment control).

 

Early treatment research has confirmed that the earlier you start treatment for HIV, the better. Early treatment limits the body’s exposure to the virus, which prevents further damage to the immune system.

 

Although the immune system is unable to control (suppress) the virus without ARVs, except in rare individuals, once a person stops ARVs, the virus begins to replicate and high levels in the blood return.

 

In the study, the goal of early treatment is not only to prevent damage to the immune system, but also to limit establishment of the viral reservoir and create a unique cohort of individuals in whom novel cure strategies can be tested.

 

The SANTHE/FRESH study will significantly contribute to HIV research and demonstrates that African researchers in African universities are conducting cutting edge science in Africa that complements global efforts in stemming the spread and eliminating the disease that has ravaged the continent

 

This article appears on the Ragon Institute website with the permission of the author, Alberto Leny.

 

Ragon Institute Media contact: Corrie Martin, [email protected], 857-268-7074