2011 Aug 3 - Pre-exposure prophylaxis, or PrEP, is currently being studied as a potential method for a person who is at risk of HIV infection to reduce their risk of becoming infected. It involves taking anti-HIV medications on a regular basis.
Earlier this year, a study called iPrEx, found that an anti-HIV pill (tenofovir + FTC, called Truvada) taken daily reduced the risk of HIV infection when used by men who have sex with men. Surprisingly, a few months later, a study called FEM-PrEP was closed early because daily tenofovir + FTC did not seem to reduce the risk of HIV infection among heterosexual women. Based on the preliminary data, it is not clear why PrEP did not work for women in the FEM-PrEP study.
Preliminary results from two new PrEP studies, known as TDF2 and Partners PrEP, were announced early in July 2011 and additional data were presented at the IAS conference in Rome. Both of these studies suggest that PrEP does work for HIV-negative heterosexual women and men.
The TDF2 study enrolled 1,219 HIV-negative heterosexual men and women from Botswana. Nearly half (46%) of the participants were women.
Half of the participants were asked to take a daily pill (Truvada, containing two anti-HIV drugs: tenofovir + FTC). The other half were asked to take a daily placebo. Participants returned to the study site every month to receive their pills.
During the study, 33 of the participants became infected with HIV. The HIV infections were distributed as follows:
- Daily tenofovir + FTC - 9 infections (7 in women, 2 in men)
- Daily placebo - 24 infections (14 in women, 10 in men)
Based on these numbers, participants using tenofovir + FTC were 63% less likely to become infected with HIV than participants using a placebo. This finding was statistically significant.
A separate analysis looked at whether tenofovir + FTC provided similar levels of protection for both men and women. The analysis found that tenofovir + FTC reduced the risk of HIV infection by 80% for men and by 49% for women. Although it appears that PrEP was less protective for women, the study was not large enough to draw firm conclusions about the effectiveness of Truvada by gender.
Results-adherence and safety
Adherence to taking a pill every day was relatively high. By counting the number of leftover pills, researchers estimated that the overall adherence rate was approximately 84%.
Daily Truvada was well tolerated. Participants taking Truvada experienced slightly higher rates of nausea, dizziness and vomiting than those taking a placebo. All the reported symptoms were mild.
Only one participant developed drug resistance during the study. This person had acute HIV infection when they enrolled in the study and was therefore HIV-positive when starting PrEP. Of the participants who were HIV-negative when starting PrEP and later became infected, none developed drug resistance.
The Partners PrEP study enrolled 4,758 heterosexual serodiscordant couples (one partner in each couple was HIV-negative and the other positive) in Uganda and Kenya. Nearly 40% of the HIV-negative partners were female. None of the HIV-positive partners were eligible for ART according to their country's treatment guidelines at the time of enrolment.
The HIV-negative partners were assigned to one of three groups: One group was asked to take a tenofovir (Viread) pill daily; one group took a pill containing tenofovir + FTC (Truvada) daily; and one group took a placebo pill daily.
The couples were followed for an average of 1.7 years. A total of 78 of the HIV-negative partners became infected with HIV during this time. The number of HIV infections in each group was as follows:
- tenofovir - 18 infections (8 in women, 10 in men)
- tenofovir + FTC - 13 infections (9 in women, 4 in men)
- placebo - 47 infections (25 in women, 22 in men)
Overall, tenofovir taken alone reduced the relative risk of HIV infection by 62% and tenofovir + FTC reduced the relative risk of infection by 73%. Both of these findings were statistically significant. Although it seemed that tenofovir + FTC provided more protection than tenofovir alone, this difference in rates of protection was not statistically significant.
A separate analysis was performed to determine if PrEP benefited both genders. The analysis found that PrEP was beneficial for both men and women. Tenofovir alone reduced the risk of infection by 55% among men and 68% among women while the combination of tenofovir + FTC reduced the risk of infection by 83% among men and 62% among women. Unlike the TDF2 study, the Partners PrEP study was large enough for researchers to make definite conclusions about the effectiveness in different genders. All these findings were statistically significant.
Results-adherence and safety
In this study, the adherence rate was extremely high: approximately 97%. The adherence rate was assessed by counting the leftover pills that participants returned to the study team. This was higher than the adherence rate observed in other PrEP studies, such as iPrEx and TDF2.
Unlike these other studies, Partners PrEP only enrolled serodiscordant couples who were in stable relationships. It's possible that being in a relationship helped the HIV-negative partner adhere to their pill-taking schedule.
Both PrEP regimens were well-tolerated and did not cause any major side effects. The participants who took anti-HIV drugs reported slightly higher rates of mild nausea and diarrhea than those taking a placebo. These side effects were more commonly reported during the first month after starting PrEP and decreased afterwards. Information on drug resistance has not been released.
Both the TDF2 and Partners PrEP studies strongly suggest that oral PrEP is safe and effective when used by heterosexual men and women. In contrast to the findings from the FEM-PrEP study, both of these studies suggest that PrEP does work for women. Further analysis is needed to explain the FEM-PrEP results.
An ongoing PrEP study, called VOICE, will provide more information about the effectiveness of PrEP among women. This study is enrolling heterosexual women and investigating the use of three different PrEP regimens: (1) daily tenofovir, (2) daily tenofovir + FTC, and (3) daily application of a vaginal gel containing tenofovir.
It is important to note that all participants in these trials, whether they were taking PrEP or a placebo, were provided with a comprehensive package of prevention services. This included risk-reduction counselling, adherence counselling, diagnosis and treatment of sexually transmitted infections, and free male and female condoms. These studies demonstrate how many additional infections are prevented when PrEP is added to a comprehensive approach to HIV prevention. PrEP may be less effective if provided in the absence of these services.
The TDF2 and Partners PrEP studies are ongoing although the provision of a placebo pill has been discontinued. After the release of the preliminary results, all participants were offered the option to remain in the study and use PrEP to reduce their risk of infection. These types of studies are commonly called "roll-over" or "open-label" studies. These studies will provide important information on adherence and risk-taking behaviours among men and women who know that the pills they are taking are effective.
CATIE Prevention in Focus article on PrEP
CATIE fact sheet on PrEP
CATIE News story on iPrEx trial
CATIE News story on FEM-PrEP trial
- Baeten J. Antiretroviral pre-exposure prophylaxis for HIV-1 prevention among heterosexual African men and women: the Partners PrEP Study. Sixth International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, Rome, abstract MOAX0106, 2011.
- Thigpen M, Kebaabetswe PM, Smith DK et al. Daily oral antiretroviral use for the prevention of HIV infection in heterosexually active young adults in Botswana: results from the TDF2 Study. Sixth International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, Rome, abstract WELBC01.
CATIE-News is written by Sean Hosein, with the collaboration of other members of the Canadian AIDS Treatment Information Exchange, in Toronto.
From Canadian AIDS Treatment Information Exchange (CATIE). For more information visit CATIE's Information Network at http://www.catie.ca
Source: CATIE: CANADIAN AIDS TREATMENT INFORMATION EXCHANGE