Partners PrEP Study:
Baeten JM et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. New England Journal of Medicine. 2012 Aug 2;367(5):399-410.
FEM PrEP Study:
Van Damme L et al. Pre-exposure prophylaxis for HIV infection among African women. New England Journal of Medicine. 2012 Aug 2;367(5):411-22.
Purpose of study
Pre-exposure prophylaxis (PrEP) is treatment given before exposure to a disease-causing agent to prevent disease. In the context of HIV, PrEP involves treatment for at-risk HIV negative individuals with daily antiretroviral therapy (ART) to prevent HIV infection. In the last decade, the efficacy of HIV PrEP has been formally studied with tenofovir alone (TDF) and tenofovir in combination with emtricitabine (FTC). The purpose of both studies reviewed here was to evaluate whether daily TDF alone (Partners PrEP) or in combination with FTC (both studies) was effective in reducing HIV-1 acquisition among heterosexual populations in Africa.
Both studies were double-blind randomized controlled trials conducted at outpatient locations. Partners PrEP (Kenya, Uganda; 2008-2010) recruited HIV-1 serodiscordant heterosexual couples (18-69 yrs); seronegative partners were randomly assigned to TDF 300 mg alone, TDF 300 mg + FTC 200 mg, or placebo. FEM PreP (Kenya, South Africa, Tanzania; 2009-2011) recruited heterosexual females (18-35 yrs) at high risk of infection; women were randomly assigned to TDF 300 mg + FTC 200 mg, or placebo. In both studies, the pharmaceutical intervention was accompanied by other prevention services (which differed between studies, and included condoms, contraceptives, male circumcision, counselling, pregnancy testing) and medication compliance was monitored through self-report, pill and bottle counts, and serum levels.
In Partners PrEP, among 4,747 serodiscordant couples there were 82 seroconversions: 17 in the TDF group, 13 in the TDF + FTC group, and 52 in the placebo group. While there were significant differences in incidence between treatment groups and placebo (p<0.001) there was no significant difference between TDF alone and TDF +FTC (67% and 75% relative risk reduction, respectively). Study follow-up was 96% with 92% reported medication adherence, and in random samples drug levels were detected in 31% of seroconverting compared to 81% of seronegative participants.FEM PrEP, on the other hand, was terminated early due to lack of efficacy. Among 2,120 seronegative females there were 68 seroconversions: 33 in the TDF + FTC group and 35 in the placebo group (p = 0.81). Study follow-up was 82%, with 95% reported medication adherence, however drug levels were only moderately higher among seronegative (37%) compared to seroconverted participants (26%). At baseline, the majority of participants (70.0%) perceived that they were at no or low risk for HIV infection, increasing to 74.8% at final follow-up.
Implications for clinical practice
These similar studies (both reported in the same issue of the New England Journal of Medicine) had some key differences that may explain the discrepant results. Partners PrEP used a seronegative-seropositive model with male and female participants (with ART protecting both male and female seronegative partners); FEM PrEP included only seronegative females at risk for HIV infection based on sexual behaviour. Biological differences due to the partner’s sex may contribute to ART effects on HIV infection. The FEM PrEP trial also included a greater loss to follow-up. While both studies identified high self-reported medication adherence and adherence by pill and bottle counts, in the FEM PrEP study detectable drug levels were low in both those who remained seronegative and those who seroconverted. This may be related to the fact that most participants in this trial perceived that they were at no or low risk for HIV infection, and may have different motivation compared to a seronegative partner in a sero-discordant relationship. Differences in the quality and nature of non-pharmaceutical prevention interventions may have further contributed to HIV risk perception, risk behaviours, and, ultimately, HIV infection.
HIV PrEP is a controversial and emerging topic in HIV prevention. It offers seronegative individuals the autonomy to prevent infection when their partner’s HIV status is positive or unknown. There have been multiple supportive studies, predominantly in heterosexual African women. Recently, the iPREX trial examined HIV PrEP in North American men who have sex with men at risk of HIV infection and study showed a risk reduction, particularly among those with therapeutic drug levels. In July 2012, the USA FDA approved the use of ART for HIV PrEP. In Canada, we are currently faced with many unresolved issues: the question of whether or not PrEP will be available, who may benefit, how to maintain adherence, cost effectiveness, and the role for behavioural interventions.
Dr. Richard Lester, Medical Head, STI/HIV Control, Clinical Prevention Services, BCCDC
CDC HIV Pre-Exposure Prophylaxis: http://www.cdc.gov/hiv/prep/
Cochrane Review of HIV PrEP (2012): http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007189.pub3/abstract;jsessionid=7E20D1687DBDA133731ED0D382D14778.d03t04