Trial halted as experimental HIV vaccine regimen fails testing in South Africa

The US National Institute of Allergy and Infectious Diseases (NIAID) announced Monday that it has stopped the HVTN 702 trial evaluating an experimental HIV vaccine in South Africa, after the study's data and safety monitoring board (DSMB) determined that the regimen was no better than placebo at preventing HIV infections. The agency noted that the DSMB did not raise any concerns regarding participant safety in the trial. 

"A HIV vaccine is essential to end the global pandemic, and we hoped this vaccine candidate would work. Regrettably, it does not," commented NIAID director Anthony Fauci. Nevertheless, he said "research continues on other approaches to a safe and effective HIV vaccine, which I still believe can be achieved."

The Phase IIb/III HVTN 702 trial, also known as Uhambo, was launched in 2016 in South Africa to test the investigational prime-boost vaccine, which is based on a regimen that had previously been evaluated in the US Military HIV Research Programme-led RV144 clinical trial in Thailand. RV144 was also the "only vaccine regimen ever to show protection from HIV," according to the NIAID. The agency added that for HVTN 702, the vaccine regimen was adapted to HIV subtype C, the most common in southern Africa. Specifically, it consists of a canarypox-based vaccine called ALVAC-HIV supplied by Sanofi, and a bivalent gp120 protein subunit vaccine supplied by GlaxoSmithKline, with an adjuvant that enhances the body’s immune response. 

The HVTN 702 study enrolled 5407 HIV-negative sexually active men and women aged 18 to 35 years in South Africa. The volunteers were randomly assigned to receive either the investigational vaccine regimen or placebo injections. The NIAID said participants received six injections over a period of 18 months, and were offered the local standard of care for preventing HIV, including access to oral pre-exposure prophylaxis, also known as PrEP. 

An interim analysis conducted late last month looked at how many people enrolled in HVTN 702 were diagnosed with HIV after at least 60% of the participants had been in the study for more than 18 months, which the NIAID said was "enough time for the vaccine regimen to stimulate an immune response." According to the findings, 129 HIV infections occurred among the vaccine recipients, and 123 occurred among those in the placebo group. The interim analysis showed no significant evidence of either decreased or increased infection rates with vaccination, the NIAID said. The agency noted that HVTN 100, a predecessor trial using the HVTN 702 regimen, had found that the vaccine was safe and induced high and boostable titers of antibodies to several HIV strains prevalent in southern Africa. 

Meanwhile, the US National Institutes of Health has invested in two other late-stage, multinational HIV vaccine trials, dubbed Imbokodo and MOSAICO. Both trials, which are sponsored by Johnson & Johnson, are testing a novel mosaic vaccine regimen that uses a different approach than the one under investigation in HVTN 702. Results for the MOSAICO study are expected as soon as 2023. 

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