Tuesday, January 31, 2023
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Three studies nudging the frontiers of HIV prevention

VaccineThere are an estimated 5,000 new HIV transmissions every day. About 70% of the 37m people living with HIV globally are in sub-Saharan Africa. Of the 1.8m new HIV transmissions worldwide in 2017, 800,000 occurred in eastern and southern Africa. New, effective prevention strategies are essential to reducing HIV transmission. So, writes Glenda Gray, research professor, Perinatal HIV Research Unit and president, South African Medical Research Council in The Conversation, what will it take to reduce HIV transmission? Prevention is her answer.

Gray writes that this is why researchers around the world are working hard to find a vaccine that is safe and effective. This requires extensive testing, starting in laboratories and then moving to animal trials. Then comes the crucial human clinical trials. A number of these are under way, running at different sites in 12 countries across four continents.

Gray writes: “These trials are being conducted under the auspices of the HIV Vaccine Trials Network. The network runs 49 clinical trial sites in nine countries with 18 ongoing trials, four of which are efficacy trials. Three trials are of particular interest as they have already been running since 2016 and are expected to close in late 2021.

“The first is known as the Antibody Mediated Prevention studies. It is testing whether a broadly neutralising antibody can prevent HIV acquisition in people. The second, called Uhambo, is testing an experimental vaccine regimen against HIV. And the third, Imbokodo, is testing an experimental vaccine regimen that is designed to offer protection against a variety of global HIV strains.

“These studies involve thousands of people all over the world, including countries hardest hit by HIV. If any of them are successful – that is, if the drugs being tested prove to be safe and effective for human use – the 30-year fight to end the HIV/AIDS epidemic will take a huge step towards victory.

“It has been incredibly hard to make a vaccine against HIV. Some of the hurdles to overcome include the genetic diversity of HIV, which is greater than any other pathogen, the lack of a good animal model, no natural human cure and the complexity of the virus’s outer structure or envelope.”

Gray writes: “The Antibody Mediated Prevention studies have 4,625 participants from the US, Brazil, Peru, Switzerland, Tanzania, Zimbabwe, Botswana, South Africa, Kenya, Malawi and Mozambique. These trials started in May 2016 and are expected to close in late 2021. The clinical trials are designed to test if a broadly neutralising antibody (VRC01), given intravenously, can prevent HIV acquisition.

“A broadly neutralising antibody is an antibody that has been found to neutralise or inactivate HIV in nonclinical experiments. Study participants are receiving intravenous infusions of the VRC01 broadly neutralising antibody every eight weeks.

“This is the furthest that a clinical trial testing the effectiveness of a broadly neutralising antibody in preventing HIV acquisition in people has progressed. These studies can potentially clarify what level of neutralisation a vaccine or antibody-based method of HIV prevention needs to achieve and maintain to provide sustained protection.”

Gray writes: “The Uhambo trial is currently under way in South Africa and aims to enrol 5,400 healthy, HIV-negative men and women aged between 18 and 35 years. This clinical trial involves a new version of the only HIV vaccine candidate ever shown to provide some protection against the virus. That vaccine candidate was investigated in the RV144 clinical trial from 2003 to 2006 in Thailand led by the US Military HIV Research Programme and the Thai ministry of health.

“The trial in Thailand delivered landmark results in 2009 when it found, for the first time, that a vaccine could confer – albeit modest – protection against HIV.

“The Uhambo regimen aims to provide greater and more sustained protection than the RV144 regimen and has been adapted to the HIV sub-type that predominates in southern Africa.

“The Imbokodo study (Imbokodo means ‘rock’ in isiZulu) is formally known as the HVTN 705/HPX2008 trial. It’s being conducted in more than 2,600 healthy, HIV-negative women in South Africa, Malawi, Mozambique, Zambia and Zimbabwe aged between 18 and 35. The vaccine regimen being tested in this trial is based on ‘mosaic’ immunogens. These are vaccine components derived from strains of HIV from different regions of the world. This approach has been designed to induce immune responses against a wide variety of global HIV strains.”

Gray writes: “Our scientific journey is remarkable. But there is some way to go before we know the full impact of these trials. All three trials are building on important breakthroughs over the past two decades. We hope that out of these three areas of exploration clarity will emerge that brings the world closer to solving what is required to protect against HIV.

“If any of the vaccines or antibodies are effective, it will unleash an enormous explosion in scientific inquiry to improve, adapt and, most importantly, bring a new form of HIV prevention to people.”

[link url="https://theconversation.com/the-three-big-studies-pushing-at-the-frontiers-of-hiv-prevention-118734"]The Conversation material[/link]

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