A four-year clinical trial involving nearly 10,000 women in East and Southern Africa has found that the vaginal microbicide gel, PRO 2000, is safe but not effective at preventing HIV infection.
The trial, known as MDP 301, found that women who applied a vaginal gel containing a 0.2 percent dose of PRO 2000 before sex were infected with HIV at about the same rate as women who applied a placebo gel.
During the course of the trial at six research sites in South Africa, Uganda, Zambia and Tanzania, 130 women in the PRO 2000 gel group and 123 in the placebo group became infected with HIV - a difference that was not significant.
More than a decade of research has so far failed to find a microbicide that protects women against sexually-transmitted HIV when applied to the vagina as a gel, foam or cream.
Hopes for MDP 301 were high after promising results from a smaller trial of PRO 2000, involving 3,000 women in Malawi, South Africa, Zambia, Zimbabwe and the United States, were released in February 2009.
The PRO 2000 gel reduced a woman's chance of contracting HIV by 30 percent, compared to a placebo gel. The finding was not statistically significant, but was enough to raise expectations that a larger trial could provide more conclusive evidence.
The MDP 301 trial did provide a definitive result, but not the one researchers were hoping for. "It's disappointing," said Dr Gita Ramjee, principal investigator for the study site in Durban, South Africa. "I've been working in this field for the last 15 years and you have to keep on trying, because we know women are being infected at a very high rate."
Women make up nearly 60 percent of adults living with HIV in sub-Saharan Africa, while young women in several southern African countries are at least three times more likely to become infected than young men.
At the Durban site, in KwaZulu-Natal Province, which has the highest HIV prevalence rate in South Africa, 6.1 percent of trial participants became infected despite receiving regular counselling to practise safe sex, and to use the condoms they were given as well as the trial gel.
"We women are depending on our men; we're supposed to mix the gel with condoms, but sometimes it's difficult to use both," said Zodwa Mbense, 32, a Durban trial participant.
Despite such challenges, around 80 percent of the trial participants used the gel consistently. "That basically means the concept of putting a gel in the vagina was acceptable," Ramjee told IRIN/PlusNews. "It's not difficult to use the gel," said Silindile Langa, 33, another participant from Durban. "I liked it."
The women learned the results of the trial two days before they were released to the public at the end of 2009; both Mbense and Langa were positive about their experience of participating in the study. "The research helped us a lot - we know our [HIV] status, we got to talk with our partners, we're empowered," said Mbense.
However, the rate of new HIV infections was only slightly lower among trial participants than the rest of the community, despite the "intensive behaviour change messages" they received.
"It raises very worrying questions about traditional prevention approaches that rely on behaviour modifications with condoms," Prof Francois Venter, president of the Southern African HIV Clinicians Society, said in a statement.
"It is quite clear we need more potent prevention interventions, and that traditional approaches, even when done very well, probably have very limited effects."
A statement from the Microbicides Development Programme, which ran the trial with funding from the UK government's Department for International Development and the Medical Research Council, said the results meant the end of the road for PRO 2000 and an entire generation of microbicide formulations that rely on similar approaches.
PRO 2000 was designed to prevent HIV by disrupting the process whereby the virus attaches to and enters healthy human cells. A "next generation" of microbicide candidates, which have shown early promise in laboratory and animal studies, incorporates some of the antiretroviral drugs (ARVs) being used to successfully treat HIV.
One such gel, containing the ARV drug, tenofovir, is already being evaluated in two trials: one where it is applied before and after sex, and another in which it is used daily and will be compared with the effects of taking an oral ARV pill every day.
Results from the first trial, known as CAPRISA 004, will be available in July 2010; results from the second, known as the VOICE study, are not expected until 2012. - PLUSNEWS