Good news in the failed HIV trial

By Hilary Bainemigisha

 

The disappointing results from a trial of a vaginal gel in South Africa will not disappoint researchers, a regional HIV prevention research expert, Dr Patrick Ndase said. Instead, it makes the ongoing trial in Uganda more hopeful for better results.

 

The trial that was expected to reduce women’s risks of contracting HIV from sex did not yielded good results, participants at annual Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle, US, were told on Tuesday. But, the researchers say, this was more to do with the behaviour of the effectiveness of the drug itself, Ndase, who is also the regional physician for Microbicide Trials Network and Partners PrEP Study, says.

 

The trial was conducted on 2,059 sexually active, HIV negative women, 18 - 30, in South Africa by the Follow-on African Consortium for Tenofovir Studies (Facts), a South African research consortium. Known as Facts 001, the trial was looking at the effectiveness of a tenofovir gel on the risk of HIV infection. It was launched in October 2011 at nine clinical trial sites in South Africa and concluded in September 2014 for laboratory analysis and the results were unveiled on Tuesday.  

 

What happened?

 

During the three-years study, researchers gave half of the women volunteers a gel containing tenofovir, a drug being used currently as an ARV, and the other half, a gel without any active drug (placebo) to insert in the vagina before and after every sexual encounter. It was hoped that the tenofovir gel would protect those in the group of the active drug from acquiring HIV. But when they compared the two groups, the infection rates were similar. In spite of the gel protection, 61 women got HIV. This was one short of the 62 women in the group that was taking the placebo who got infected during the trial period. The 123 women who got HIV make up 4% infection rate.

 

The trial analysis however revealed that most women in the study did not use the gel. Prof. Helen Rees, co-chair of the trial, agreed that the method of delivery, which trusted the participants to insert the gel themselves, was not ideal.

 

“A product that requires women to apply the gel before sex did not meet the needs of the majority in our study. Most of them were young, single and lived with their parents,” Rees said in a press statement released by Facts 001. “We need methods that are easier for women to incorporate into their lives.”

 

The problem

 

Ndase said all the studies of the Tenofovir gel which failed to duplicate the 2010 study success which showed that tenofovir gel was 39% effective, have been based on the trust that the user will actually apply the gel.

 

“Adherence in this Facts 001 study was 22%! In other words, 22% of the blood samples that were collected from the trial participants had consistent drug detection.  A trial which does not control the application of the drug is bound to fail due to adherence. Women in Africa have too many inconveniences to be able to apply the gel before and after sex.”

 

Results also showed a trend of modest protection among the small proportion of women in the trial who appeared to have used the product consistently. But they were not enough to change the overall outcome of the trial.

 

Similar trials are going on in Uganda, Malawi, South Africa and Zimbabwe by the Microbicide Trials Network (MTN). 2,629 women are given vaginal rings, inserted deep around the cervix. The ring stays for a month releasing the ARV drug dapivirine into the vagina to determine if it can protect the woman from HIV infection through sex. Results are expected in late 2015 or early 2016. A similar trial by the International Partnership for Microbicides (IPM) is enrolling 1,950 women at sites in Uganda and South Africa. Results are expected in late 2016.

 

Ndase says unlike other trials whose products are user-dependent, these ones are testing rings, implanted at the site. Because women only need to replace the ring once a month, it could provide a discreet and easy-to-use new method of protection.

 

“When women come to the site for a new ring after a month, researchers are able to test the old ring to see whether the drug in it has been used up. They are able to know if the woman removed the ring during the month. This helps us to monitor adherence during the study rather than trust the volunteers and wait till the trial ends before we can determine adherence rates.”

 

Tenofovir works

 

Ndase says all information shows the drug Tenofovir works to block HIV from infecting the recipient. A 2010 trial by the Centre for the AIDS Programme of Research in South Africa (Caprisa), showed that the tenofovir gel was 39% effective in reducing the rate of HIV infection among over 900 women in the KwaZulu-Natal province, South Africa.

 

Tenofovir, used as pills among discordant couples (where one partner is HIV positive and one is not) in Uganda and Kenya showed a 96% reduced the risk of HIV infection. Similar studies in UK and France among high risk men who have sex with men, showed a 86% reduced the risk.

 

Ndase says Tuesday’s results prove that for any ARV-based prevention technology to work, it must be user friendly, convenient and acceptable for the community that is being targeted to actually want, demand and use them.