Microbicides

Headed by Salim Abdool Karim

The highest burden of HIV infection is in women younger than 30 years, making prevention interventions targeting adolescents and young women a high priority. Various sexual coupling patterns place young women at high risk, including partnering with older men who are more likely to be infected, multiple concurrent relationships, low marriage rates, low condom use rates, and limited skills in negotiating safer sex practices. Gender-based violence increases vulnerability, and poverty increases reliance on transactional sex for survival. Women are often unable to convince their male partners, especially husbands and regular partners, to use condoms.

Notwithstanding the greater vulnerability of women, current options to reduce acquisition of HIV infection remain limited for women. New technologies to prevent the sexual transmission of HIV in women are urgently needed. Even a partially effective microbicide could have a profound impact on the dynamics of HIV transmission.

Modelling the modest effects of CAPRISA 004 trial demonstrated that, in South Africa alone, tenofovir gel could avert 1.3 million new HIV infections and over 800,000 deaths over the next 2 decades. Hence, CAPRISA is conducting research aimed at discovering a safe and effective technology for women to protect themselves from HIV infection.
 

Next steps after the CAPRISA 004 Tenofovir gel trial

In 2010, the CAPRISA 004 trial showed that tenofovir gel, applied before and after sex, reduced HIV incidence by 39% (95% confidence interval 6 to 60), providing proof-of-concept that an antiretroviral agent can prevent sexual transmission of HIV in women. As part of a post-trial access initiative, the women from the CAPRISA 004 trial were invited to join the CAPRISA 008 trial which is assessing whether tenofovir gel provision can be effectively integrated into family planning clinics.

The CAPRISA 004 tenofovir gel trial presented a unique opportunity to conduct a range of ancillary clinical and laboratory studies on topical tenofovir to further advance the microbicide field. The TRAPS Program (Tenofovir gel Research for Advancing Prevention Science) has been established to assess the effects of genital inflammation in the genital tract that may influence the risk of HIV infection and that may impact the effectiveness of microbicides like tenofovir gel. CAPRISA is also a member of the Microbicide Trials Network (MTN) and is conducting MTN 020 to assess the safety and effectiveness of the Dapivirine ring.

CAPRISA participated in the VOICE trial (MTN 003) which did not demonstrate an HIV prevention effect of tenofovir-containing daily tablets and gel, as the women did not use the products despite returning unused product in keeping with high adherence. CAPRISA also supported, but did not participate in, the FACTS 001 trial which did not confirm the effectiveness of coitally-related tenofovir gel as few women were able to maintain high adherence in the trial.  The disappointing results from the VOICE and FACTS 001 trials have highlighted the adherence challenges for women on tablets and gels for HIV prevention. As a result, CAPRISA is now conducting the HPTN 077 and CAPRISA 014 trials to assess a slow-release injectable form of the integrase inhibitor, cabotegravir.