AIDS Alert International
HIV Prophylaxis Still has no Clear Cut Answer
Researchers continue to study the use of a chemoprophylaxis for the prevention of HIV infection among at-risk groups around the globe, but the results public health officials hope to find remain elusive.
A recent study conducted by investigators with Family Health International of Research Triangle Park, NC, found a very good safety profile among the 936 HIV-negative women enrolled in a 12-month, clinical trial testing tenofovir as a daily prophylaxis against HIV infection. But there were no significant findings regarding efficacy, says Leigh Peterson, PhD, a scientist and project leader for the West Africa Oral Tenofovir Study, which was initiated in Ghana, Cameroon, and Nigeria.
"We obtained a total of eight seroconversions during this study out of a projected number of 30," Peterson says. "We projected 30 based on the epidemic in a nearby country with a similar population, but it's really hard to have a very definite number, and even if you do a study in an identical population things change over time."
While the low number of seroconversions was a positive outcome, there was not a significant difference between the seroconversions among the placebo group and the tenofovir group because the numbers were too small to compare, Peterson explains.
"There were only two participants who became infected while on tenofovir, and the remainder were on placebo," Peterson says.
Although some might say the number of seroconversions on tenofovir was one third of those on placebo, this could have been the result of pure chance, she adds.
The trial ran into some difficulties, including the closing of a couple of sites because of compliance issues and political barriers. Also, the women enrolled in the trial had a far greater pregnancy rate than anticipated, and when participants became pregnant, they were taken off the study drug, Peterson says.
The main factor that might have led to an overall reduced seroconversion rate is the intense risk reduction counseling, and all participants were given condoms to use with every act of sex, Peterson explains.
"Also people who join studies might be different from people who don't join studies, and they might be people who have a tendency to practice safer sex," Peterson notes.
"While this is good news for public health to have a decreased overall HIV incidence in the study, relative to what we might have seen without intensive counseling, what we also did is we obtained only eight seroconversions instead of 30," Peterson says. "So we didn't have the information necessary to get a statistically significant result about whether tenofovir was effective or not."
The Centers for Disease Control and Prevention (CDC) of Atlanta, GA, and the National Institutes of Health also have ongoing or planned studies using an oral medication as a strategy to prevent HIV infection, and FHI is looking at sites to include in future research on the topic, Peterson says.
The FHI study was the first one that looked at people who were not infected with HIV and were using tenofovir as a prophylaxis, Peterson says.
Researchers theorize that a chemoprophylaxis will be most useful in high-risk populations since studies are focusing on the prevention method as a daily pill that will need to be taken indefinitely, she notes.
"If it's found that tenofovir works as a daily dose, what we need to do is see if it works for women when it's vaginally applied, whether daily or coital-dependent," Peterson suggests. "There are planned studies to look at a vaginal gel containing tenofovir."
Also, there will need to be additional dosing studies to figure out exactly which populations might use it as a microbicide.
"What we need to do is find out if it works as an oral medication taken daily or vaginally, and how frequently dosing needs to be, and the different types of regimens will be more prevalent for different populations," Peterson says.
Another recent study conducted primarily by CDC investigators looked at the potential impact of HIV chemoprophylaxis strategies among men who have sex with men (MSM) in the United States.1
Researchers are calling strategies that have HIV-negative, at-risk people taking tenofovir pills daily a pre-exposure prophylaxis (PREP), which is similar to what international travelers frequently take when they are taking anti-malarial pills while traveling in countries where malaria is endemic, says Kamal Desai, MSc, PhD, a research associate with the Department of Infectious Disease Epidemiology at the Imperial College London and St. Mary's Hospital in the United Kingdom.
The leading candidates for a PREP to prevent HIV infection are tenofovir and Truvada, which is a combination of tenofovir and emtricitibine, Desai says.
"There are clinical trials going on in America, Peru, and parts of Africa where they are testing whether a chemoprophylaxis is efficacious in protecting against HIV infection," Desai says. "Those studies may be concluded in 2007 or 2008."
If the studies show that a PREP for HIV is efficacious, then that's where the CDC's modeling study will be relevant because it addresses the costs and benefits of a PREP.
Since the question of efficacy is unanswered, the CDC study makes assumptions that a PREP is efficacious, although not 100 percent efficacious since the primate studies have suggested an efficacy of about 50 percent, Desai says.
The modeling study also makes an assumption about adherence at a population level and uses a cost of the drug of $14 per daily dose, based on the current cost of tenofovir in the United States, he says.
"The cost of the pills amounts to 80 percent of the entire costs of a PREP program, while the other costs are support services for participants in chemoprophylaxis, initial medical screening, and ongoing medical exams at three-month intervals, including HIV tests," Desai says. "A small number of people would not be eligible because of some liver conditions."
Adding the support service costs together, the study estimates the cost over a five-year period would be about $5,000 per participant. The cost of providing a daily pill to 15,000 very high-risk MSM in New York City, for instance, would raise the entire program costs to $400 million-$500 million over five years, Desai says.
"If you look at the HIV infections it would have prevented, then it can have a cost savings," Desai explains. "You're preventing future costs related to HIV care in those people in whom infection has been prevented."
Even at a 50 percent efficacy rate, with 50 percent adhering to the daily pill regimen, then there would be 1,600 to 1,700 HIV cases prevented over five years, Desai says.
"Then combine that with the costs and you find a cost-effectiveness ratio of $12,000 per quality-adjusted life years," Desai says. "As a general rule, if that cost per life year that you buy falls under $50,000, it's considered an okay investment."
The key to a PREP success would be to target only high-risk populations because this is not the same as a vaccine or male circumcision, which has proven to be highly efficacious, Desai says.
"So you have to see this in the right context," he adds. "This may serve as a kind of stop-gap until other interventions that are better and more effective can be found."
The PREP's risks are that the drug is not perfect, and it may result in some people becoming infected and continuing to take the drug for some months before they learn their infected, Desai explains.
"And for that period of time they're taking tenofovir, they're effectively on monotherapy, and this opens the door to emergence of drug-resistant virus that can be transmitted to other people in the population," Desai says. "This is a concern; even if the drug were very efficacious, I would be watchful for HIV strains resistant to tenofovir."
Peterson says that follow-up results from one of the two women who had used tenofovir as a PREP and then became HIV infected, did not show evidence of resistance mutations.
"Further research will be done on her, as well as on the second woman," Peterson says. "It's important to look at this, but it's not going to tell us a whole lot because we only have two cases."
Another factor to consider with using a PREP is that it could have just enough impact on a high-risk population to decrease overall prevalence, but not to eradicate it, and this means there will remain a need for risk-reduction counseling and other prevention messages, Desai says.
While the PREP might not be enough to stop the epidemic, it could have a cascading effect that will indirectly lead to a weakening in the chain of transmission, Desai says.
Reference:
- Desai K, et al. Modeling the potential impact of HIV chemoprophylaxis strategies among men who have sex with men in the United States: HIV infections prevented and cost-effectiveness. Presented at the AIDS 2006 - XVI International AIDS Conference, held Aug. 13-18, 2006, in Toronto, Canada; Abstract: THAD0101.
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