By Agnes Asiimwe
Scientists excited about a very promising trial
A powerful new HIV prevention tool may be on the horizon. Scientists are saying they could be on the verge of ascertaining whether taking anti-retroviral drugs before exposure to HIV could be an effective prevention tool. The Pre-exposure prophalyxis (PrEP) trial is going on in Botswana, Kenya, Uganda, South Africa, Thailand and USA. African researchers involved in the study say they are very hopeful
PrEP refers to an experimental HIV prevention strategy that would use anti-retrovirals to protect HIV negative people from HIV infection. Under the strategy that is currently being tested, HIV negative people would take a single drug, or a combination of drugs, daily in hopes that this would protect them against HIV infection. Two ARVs are being tested in the PrEp trials: tenofovir disoproxil fumarate (TDF), or Viread, and TDF + emtricitabine (FTC), also known as Truvada. According to the researchers, PrEP seems promising. This is a shot in the arm for the researchers after a series of disappointing results from several past clinical trials.
The first preclinical evidence to indicate that PrEP might be effective came from animal studies conducted in 1995. Preclinical data shows that administration of certain ARVs can effectively block infection in monkeys. In one study by the US Centers for Disease Control (CDC) researchers found that oral administration of antiretroviral drugs before and after exposure to SHIV, the monkey equivalent of HIV, effectively prevented rectal infection in monkeys. CDC also found that when applied as a gel prior to vaginal SHIV exposure, a single antiretroviral drug was just as effective as two antiretroviral drugs in preventing SHIV infection in female monkeys. This has sparked a lot of excitement among researchers about the potential of PrEP. If the monkey model proves to reflect human dynamics of transmission, it suggests that PrEP regimens may prove effective.
Seven large clinical trials are in the process of testing whether this strategy can also work in humans. The researchers warn, however, that although data from the animal studies is encouraging, the implications for humans are not yet known as there are many differences in the immune response of monkeys and humans. Only human trials can tell to what extent PrEP is safe and effective in reducing HIV transmission in humans.
Results in humans in the Phase II PrEP study checked for safety among 936 HIV negative women in Cameroon, Nigeria and Ghana. They took a pill daily for one year and we didnt see any side effects and it indicated that it was relatively safe, said Dr Patrick Ndase, the regional physician for the Microbicide Trials Network and the Partners PrEP study.
Phase III of the PrEP clinical trial in humans is being carried out in diverse populations injection drug users in Thailand, gay men in South Africa and USA, sero-discordant couples couples in which one partner has HIV and the other does not – in Uganda and Kenya, and high risk men and women in Botswana and South Africa. Uganda and Kenya have eight sites studying HIV discordant couples. From these sites, 3,900 discordant couples will be enrolled. Of these 1,300 will be taking tenofovir, 1,300 taking Truvada and 1,300 taking a placebo, said Dr Edith Nakku, the coordinator and co-investigator at the Kampala Site. Why PrEP is so important, she said, is because the success of PrEP would end many HIV discordant couples dilemma. Some abstain, some choose to separate, some use condoms, some dont use condoms, if PrEP works, these couples will live safely with each other. Many are young people who want to start families, said Dr Nakku.
Discordant couples are the largest risk group for HIV infection in Africa and recent data indicate that one out of every two new HIV infections in Africa occur in marriage or stable relationships. But many discordant couples are unaware of their status, which puts the negative partner at risk. A 2008 modes of transmission study by Makerere University Kampala researchers revealed that 650,000 Ugandans are unknowingly living with HIV positive sexual partners and almost 85,000 of these individuals, or 13%, will contract the virus in 2009 if nothing is done to increase awareness about the situation. Less than 30% of couples in Africa test for HIV together as a couple. This is because men are reluctant to be tested and thats alongside the assumption that their partners HIV status is the same as theirs. Yet, men are the infected partner in many cases. We tell people that your partners status is not necessarily your status, said Ndase.
Inclusion criteria for the study are stringent. One must be healthy with normal liver, kidney and blood count tests. The HIV infected participants must be in good health and not yet eligible for anti-retroviral treatment. Couples, who must first sign consent forms (the forms are translated into vernacular), attend counseling monthly, get free condoms and are treated for any sexually transmitted infections. The trial has tremendously encouraged couple testing, said Dr Nakku. Enrollment will go on until 2010. Trial results are expected in 2012 and 2013. â€œBut if the drug works then we dont have to wait till 2013, said Dr Ndase. We are very hopeful. We dont know how it will pan out but we hope that it will be useful to prevent HIV acquisition, said Nakku.
Alongside PrEp is another related study known as VOICE, which will be looking at ARV containing microbicides and will test the oral and vaginal delivery of ARVs to prevent HIV infection. This study is recruiting women only 4,200 participants from Zambia, Zimbabwe, South Africa, Malawi and Uganda. Its a tool for women, under womens control to give women a voice, said Dr Ndase, who is coordinating this study, alongside the PrEP study. Increasingly, men with multiple sexual partners are becoming the main driver of the epidemic in Sub Sahara Africa. An effective microbicide could provide women with a prevention method they are in charge of. In the trial, some women will take a pill while others will apply a gel. This is expected to start in May.
For every two people who start on antiretroviral treatment somewhere in the world, five are newly infected. UNAIDS estimates that about 7,500 people become newly infected everyday. Leading scientists have concluded that averting the AIDS epidemic wont come through increasing the number of people on antiretroviral therapy but through prevention of new infections.Â Innovations like PrEP are therefore a step in the right direction.
These studies are being sponsored by the Bill and Melinda Gates Foundation, CDC, USAID, US National Institutes of Health (NIH) and Family Health International.