•The antibody trial in Kisumu started in 2017 where 61 women were selected and enrolled in the study, expected to take five years. Each participant will be in the study for about two years. Trial results are expected in 2022.
•If the trial is successful, it will bring a new form of HIV prevention to people.
There are an estimated 5000 new HIV transmissions every day. Around 70 per cent of the 37 million people living with HIV globally are in sub-Saharan Africa.
Of the 1.8 million 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 what will it take to reduce HIV transmission? Prevention.
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 underway at the moment, running at different sites in 12 countries across four continents.
These trials are being conducted under the auspices of the HIV Vaccine Trials Network. The network currently 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’s 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’s 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.
The antibody search
The Antibody Mediated Prevention studies have 4625 participants from Kenya, the US, Brazil, Peru, Switzerland, Tanzania, Zimbabwe, Botswana, South Africa, 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.
In Kenya, the US Centre for Disease Control is conducting the trial from the KEMRI Clinical Research Centre in Kisumu County.
Enrollment of the intravenously (IV) delivered antibody in adults at risk for HIV infection in Kisumu began in January 2017 when 600 women were initially pre-screened. Following this, 150 of the women went through to the screening process and 61 were selected and enrolled in the study. The study is expected to take five years and each participant will be in the study for about two years.
In traditional vaccine studies, people get a vaccine and researchers wait to see if they produce antibodies in response. In the AMP Study, participants receive the antibody directly by IV infusion. Laboratory studies have shown that the antibody used in this study (VRC01) stops up to 90 percent of HIV strains, and thus it is considered a broadly neutralizing antibody.
Study volunteers randomly receive either a higher dose of the antibody, a lower dose, or a placebo. Neither the volunteers, nor the investigators, know who receives which type of infusion during the study. The volunteers receive a total of 10 infusions, once every 8 weeks, and they are then followed for an additional 20 weeks.
They also receive standard prevention interventions including oral pre-exposure prophylaxis (PrEP). The trials will examine the safety, tolerability and effectiveness of the antibody infusion. Trial results are expected in 2022.
Many scientists believe that a vaccine developed using broadly neutralizing antibodies could protect healthy people from HIV infection. The AMP Studies are contributing to the assessment of this hypothesis. Additionally, the studies aim to clarify what level of broadly neutralising antibodies a vaccine, or other long-acting HIV prevention method, needs to achieve and maintain for long-term protection from HIV.
A broadly neutralising antibody is an antibody that has been found to neutralise or inactivate HIV in non-clinical 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.
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 enquiry to improve, adapt and, most importantly, bring a new form of HIV prevention to people.
Glenda is the president, South African Medical Research Council. The full version of this article was initially published in the Conversation. Additional information is from CDC.