SCIENTISTS at the International AIDS vaccine conference in Bangkok last month took note of a combined approach to tackle AIDS by way of a vaccine along with prophylaxis drugs/microbicides. While it’s not clear when HIV vaccine RV144 will be made available to the public, the importance of pre-exposure prophylaxis (PrEP) drugs cannot be undermined, reports Rashmi Menon
The quest for HIV vaccine has seen much optimism in the last one decade. Apart from advances made in HIV vaccine research, the scientific community has also taken note of a combined approach, which includes prophylaxis drugs/microbicides to tackle the syndrome.
This approach found many takers among eminent scientists who attended the International AIDS vaccine conference held in Bangkok last month. While Thailand’s RV144 vaccine, the first in the last 30 years of research has shown efficacy (31 per cent after a three-year follow up), scientists are not certain when this or a better vaccine might become available to the public. Meanwhile, the threat of new infections has not reduced with incidence of infection having gone up in certain groups. Pre exposure prophylaxis (PrEP) anti retroviral drugs (ARV) and vaginal microbicides are being considered a potential preventive intervention strategy.
Although the story of PrEP began in 1995 when it was tested on macaques, development in the field took off only in 2005, when the first phase I trial of HPTN-050 tenofovir (an ARV) vaginal gel, was carried out on sexually active HIV negative women. Since then, eight more clinical studies have taken place, with 2007 witnessing many phase II and III trials.
Using PrEP as a preventive interventional strategy for HIV negative persons indulging in high-risk behaviour emerged from prophylaxis given for malaria or Prevention of Parent to Child Transmission (PPTCT), where anti retroviral (ART) drugs were given to HIV positive pregnant women during labour or delivery and to new born babies, in case they were being breastfed, to lower the incidence of virus transmission.
So, when a person takes PrEP, the drugs will already be in his/her body when the exposure to HIV virus occurs, and thereby, prevent infection or treat it immediately. What PrEP means is using antiretroviral medications (ARVs) to reduce the risk of HIV infection in HIV negative persons. A microbicide aims to study whether substances could be used in the vagina and/or rectum to reduce the risk of HIV transmission.
In microbicides, the results of one per cent Tenofovir gel, CAPRISA 004, in young women in Durban, South Africa, in July 2010, was a turning point in the field of PrEP/ vaginal microbicides. In fact, the year saw two trials showing very good efficacy levels, with scientists considering it as a successful year in PrEP/ microbicide research. Then came the oral PrEP iPrEx clinical study results in November, 2010, that focused on men having sex with men (MSM). The study highlighted 50 per cent efficacy, which researchers say, is excellent.
In terms of adherence to PrEP/vaginal microbicides, the researchers found heterosexual men and women to have the highest (78 pc) in TDF2 clinical trial, followed by MSMs and trans women in iPrEx study (73 pc), said Dr Suwat Chariyalertsak, who was the principal investigator in the Thailand arm of the iPrEx trial (carried out in 11 sites). Even the HPTN052 clinical study done on heterosexual discordant couple (where one partner is HIV positive and the other is negative) showed very good efficacy at 96 per cent.
Compliance, side effects and drug resistance are some of the challenges that have riddled the success of PrEP. Researchers have found that people are not compliant to PrEP course, especially daily consumption of drugs. For instance, during the iPrEx clinical trial, 110 out of the 2,499 men became HIV positive.
Of these, 10 were detected positive soon after the trial began, indicating these men were already carrying the virus but did not come out positive during the screening test as the virus may have been under incubation period. Incidentally, two of these HIV positive men developed drug resistance too.
“You need to make sure that before recruiting people for PrEP trials, they are HIV negative. Else chances of resistance will be high,” Dr Suwat, who works in the Department of Community Medicine, Chiang Mai University, Thailand. Trial participants also had side-effects such as nausea, dizziness, vomiting and, in some, decrease in bone mineral density.
On cost-effectiveness, Dr Deborah Birx, director, Division of Global HIV/AIDS, Centers for Disease Control and Prevention (CDC), USA, believes that if a country has limited funds then it is better to go for tried and tested methods like male circumcision, PPTCT, regular HIV testing and behavioural change, since these are more cost effective than PrEP.
A web based survey conducted by HIV Vaccine Trial Network (HVTN) on MSM and trans women-focused HIV vaccine trial found that only 31 per cent respondents considered taking PrEP within the next year. “There is lot of excitement about it (PrEP) but not a lot of enthusiasm to use PrEP among these participants,” HVTN executive director Dr Jim Kublin pointed out.
*HIV Vaccine Trials Network (HVTN), an international collaboration of scientists and educators, supported by National Institute of Allergy and Infectious Diseases (NIAID) of the US National Institutes of Health (NIH) aids the process of preventive HIV/AIDS trials.
*Speaking to Deccan Herald, HVTN Executive Director Dr Jim Kublin explains, “If you look at the cost of prophylaxis and treatment of those people who will get infected due to poor adherence and moderate efficacy, we will still see millions of people becoming HIV infected. With a vaccine, the cost and benefit analysis is in favour of a combination of these prevention modalities, not just a vaccine but not just drugs as prevention.”
*The network has not facilitated vaccine trials in Asia, especially India. While blaming government regulations and bureaucracy, Kublin points out that “there are ongoing discussions to improve the clinical trial regulatory approvals to facilitate future HIV clinical trials in India.”
*On research involving link between HIV and malaria in Malawi, Africa, he explains, “Other infections like malaria activates the immune system and increases the viral load of HIV in the body. So when one has malaria, the person’s immune system is activated, the HIV virus goes up and when virus level is more, the person is more likely to transmit the virus. It could be a terrible synergy between HIV, malaria and global climate change.”
(Published in Deccan Herald)