Scientists have tested the “first anti-HIV pill to provide effective protection against the disease”, The Independent has reported.
The news comes from an international study looking at whether a pill combining two antiviral drugs could reduce new HIV infections among 2,500 HIV-negative men and transgender women who have sex with men. This population is considered to have higher risk of exposure to the virus. Compared with a dummy placebo drug the daily pill reportedly cut the risk of contracting HIV by 44%. All participants had also received condoms and counselling on how to reduce the risk of contracting HIV.
While the group receiving antiviral drugs did have a lower rate of new infections, it should be noted that the drug did not provide full protection – 36 people were newly infected, compared with 64 in the placebo group. While the rate of side effects was low in both groups over the three-year study, further research is also needed to establish dosage, safety and tolerance over longer periods.
While this preliminary research is encouraging, the eventual development of drugs to prevent HIV infection would not diminish the importance of awareness and condom use, which are two key tools for preventing the spread of HIV and other sexually transmitted infections.
Where did the story come from?
The study was carried out by researchers from The University of California at San Francisco and was funded by the US National Institutes of Health and the Bill & Melinda Gates Foundation. It was published in the peer-reviewed New England Journal of Medicine.
The research was covered well by the BBC, which highlighted that this treatment is not ready for widespread use. The BBC also indicated some of the potential issues that would need to be considered if a prophylactic HIV treatment were to become available, such as drug resistance and the impact a drug for preventing HIV transmission might have on attitudes towards practising safer sex. The Independent said that the pill provided effective protection against HIV. Some might wrongly assume this to mean the pill was 100% effective in preventing HIV transmission. Further in the article they do, however, highlight that the antiviral drug only caused a reduction in transmission rate.
What kind of research was this?
This was a randomised controlled trial that looked at whether a prophylactic combination treatment of two drugs could lower the risk of infection with HIV in a group of men and transgender women who were considered to be at high risk of being exposed to the virus.
Antiretroviral therapies are used in the treatment of HIV (HIV is a type of virus known as a ‘retrovirus’). It is suggested that antiretrovirals may decrease viral transmission to uninfected partners and also decrease mother-to-child transmission. These drugs may also be used as a post-exposure prophylactic (preventative) treatment if a person has been exposed to fluids potentially infected with HIV. However, this use requires that people recognise that they might have been exposed and that they start therapy within 72 hours of exposure.
The researchers said that pre-exposure to antiretroviral drugs had been shown to lower infection rates in mice and primates that had been transplanted with HIV-infected human cells. They also said that a recently published study had demonstrated that a vaginal gel containing an antiretroviral drug had reduced HIV infection rates by 39% among women.
The researchers wanted to see whether a daily pill containing two antiretroviral drugs would reduce the transmission rates in a group of people at higher risk of being infected with the virus, and also to examine whether there would be side effects from the treatment. The two antiretroviral drugs, emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF), were combined into a single FTC-TDF pill (commercial name Truvada).
What did the research involve?
This was a multinational study, called the Preexposure Prophylaxis Initiative (iPrEX) trial. The study followed 2,499 HIV-negative people recruited from Peru, Ecuador, South Africa, Brazil, Thailand and the United States. The study was carried out from July 2007 to December 2009.
The study recruited participants that were male sex at birth and had sex with men. The participants were over 18 and were HIV-negative. The study included participants that were assessed to be at risk of HIV infection based on their sexual practices, such as having multiple partners, having sex without a condom, having an infected partner or having unprotected sex with a partner of unknown HIV status.
Study visits were scheduled every four weeks, and at each visit the participants received risk-reduction counselling and were provided with either the FTC-TDF study drug or placebo, as well as condoms. At each visit the participants were asked if they had missed taking any pills, and the pills left from the previous month’s prescription were counted. The participants were also tested for HIV antibodies every four weeks.
Every 12 weeks the participants were interviewed to see whether they had engaged in higher risk sexual behaviour over that time. Every 24 weeks the participants had a physical examination and were tested for sexually transmitted infections.
If the participants reported that they may have been exposed to HIV, they were given post-exposure prophylactics and temporarily stopped the study drug.
The participants were followed for up to 2.8 years but on average (median) for 1.2 years.
What were the basic results?
The researchers found that the sexual practices were similar in the placebo group and the FTC-TDF group. After enrolling in the study, the total number of sexual partners with whom the respondent had receptive anal sex decreased, and the percentage of those partners who used a condom increased. There was no difference between the groups in the number of other sexually transmitted infections.
The researchers said that the TDF drug can impair kidney function. They found that blood creatinine levels (a measure of kidney function) were elevated in five people in the FTC-TDF group (<1% of the group) but in none of the placebo group. More people reported nausea in the FTC-TDF compared with the placebo group (22 people compared with 10 people; p=0.04). Likewise, unintentional weight loss of 5% or more was reported among more of the FTC-TDF group than the placebo group (34 people compared with 19 people; p=0.04).
One hundred participants became infected with HIV during the study. Thirty-six of these were in the FTC-TDF group and 64 in the placebo group. This meant that there was a 44% reduction in the incidence of HIV in the FTC-TDF group compared with the placebo group (95% confidence interval 15 to 63; p=0.005).
The researchers found that, on average (median), the participants reported having taken 89-95% of the pills that they had been prescribed. The researchers measured the levels of the study drug in a blood sample provided by the participants. They found that 54% of participants who were considered “on treatment” on more than 50% of days had a detectable level of FTC-TDF in their blood. The researchers found that in the FTC-TDF group participants with detectable levels of the study drug in their blood had 12.9 times lower odds of HIV infection compared with those with undetectable drug levels (95% CI, 1.7 to 99.3; p<0.001).
How did the researchers interpret the results?
The researchers said the “once-daily oral FTC-TDF provided 44% additional protection from HIV among men or transgender women who have sex with men” when given alongside a comprehensive package of prevention services. However, they highlighted that, although this was a significant protection and “slowed the spread of HIV in this population”, it was lower than they had predicted it would be. The researchers said that they had chosen to study the treatment on men and transgender women who have sex with men as HIV prevalence is higher in this population than in other groups in almost all countries, but that the “optimal regimen for pre-exposure prophylaxis has not been established” and data from the participants in this study cannot be applied to other populations.
Current research is reportedly testing the drug as a pre-exposure prophylaxis in other populations.
This was a well-conducted study that assessed the use of an oral prophylactic treatment for HIV in a higher risk population. Although the treatment did reduce the number of new infections in this group compared with placebo, it did not prevent transmission entirely. The researchers also highlighted that the participants’ behaviour changed in some ways after enrolment in the study, including increased condom use and a reduction in higher risk behaviour. These changes may reflect the influence of the additional services, such as counselling, testing and dispensing of condoms, that were provided alongside the study drugs.
The researchers caution of the possible risk of prescribing the drug out of a trial setting. They suggest that the positive moves towards prevention displayed by the participants may not necessarily be adopted by users due to increased expectation of the benefits of the drug. Alongside these concerns, further research will be needed to establish the long-term safety and tolerance of the treatment and to define the minimum protective drug concentration.
As it stands, this research provides encouraging but preliminary evidence that prophylactic antiretroviral treatments could provide an additional benefit alongside safer sex practices and education among a specific high-risk population. As such, it may potentially slow down the spread of HIV within similar populations, but needs further testing among other social groups.
While the development of effective drug-based HIV prophylaxis would be an important step in the right direction, it should be emphasised that this would not diminish the importance of barrier methods of contraception, such as condoms, which remain the best method of preventing transmission of HIV and other sexually transmitted infections.
Analysis by Bazian
Edited by NHS Website
Links to the headlines
The Independent, 24 November 2010
BBC News, 24 November 2010
Links to the science
New England Journal of Medicine, November 23 2010