Effectiveness and Safety of Tenofovir Gel, an Antiretroviral Microbicide, for the Prevention of HIV Infection in Women

Abstract

on behalf of the CAPRISA 004 Trial Group ‡ The Centre for the AIDS Program of Research in South Africa (CAPRISA) 004 trial assessed the effectiveness and safety of a 1% vaginal gel formulation of tenofovir, a nucleotide reverse transcriptase inhibitor, for the prevention of HIV acquisition in women. A double-blind, randomized controlled trial was conducted comparing tenofovir gel (n = 445 women) with placebo gel (n = 444 women) in sexually active, HIV-uninfected 18-to 40-year-old women in urban and rural KwaZulu-Natal, South Africa. HIV serostatus, safety, sexual behavior, and gel and condom use were assessed at monthly follow-up visits for 30 months. HIV incidence in the tenofovir gel arm was 5.6 per 100 women-years (person time of study observation) (38 out of 680.6 women-years) compared with 9.1 per 100 women-years (60 out of 660.7 women-years) in the placebo gel arm (incidence rate ratio = 0.61; P = 0.017). In high adherers (gel adherence > 80%), HIV incidence was 54% lower (P = 0.025) in the tenofovir gel arm. In intermediate adherers (gel adherence 50 to 80%) and low adherers (gel adherence < 50%), the HIV incidence reduction was 38 and 28%, respectively. Tenofovir gel reduced HIV acquisition by an estimated 39% overall, and by 54% in women with high gel adherence. No increase in the overall adverse event rates was observed. There were no changes in viral load and no tenofovir resistance in HIV seroconverters. Tenofovir gel could potentially fill an important HIV prevention gap, especially for women unable to successfully negotiate mutual monogamy or condom use. W omen are disproportionately affected by the Acquired Immunodeficiency Syndrome (AIDS) epidemic in Africa, the region that accounts for 70% of global burden of Human Immunodeficiency Virus (HIV) infection (1). Current HIV prevention behavioral messages on abstinence, faithfulness, and condom promotion have had limited impact on HIV incidence rates in women, especially in sub-Saharan Africa, where young women bear the greatest HIV burden (2). The search for new technologies to prevent sexually transmitted HIV infection over the past three decades has had limited success. Only five of 37 randomized controlled trials, which tested 39 HIV prevention strategies, have demonstrated protection against sexual transmission of HIV infection (3). The successful trials tested medical male circumcision in South Africa (4), Kenya (5), and Uganda (6) (combined effectiveness in reducing HIV acquisition was 57%), sexually transmitted infection (STI) treatment in Tanzania (effectiveness in reducing HIV acquisition was 42%) (7), and a HIV vaccine combination in Thailand (effectiveness in reducing HIV acquisition was 31%) (8). Hence, HIV prevention technologies that women can use and control remain a pressing priority (9).Microbicides are products that can be applied to the vagina or rectum with the intention of reducing the acquisition of STIs, including HIV. An effective microbicide has the potential to alter the trajectory of the global HIV pandemic (10). Over the ...

The influence of social constructs of hegemonic masculinity and sexual behaviour on acceptability of vaginal microbicides in Zambia

“…The first is the CAPRISA 004 Phase IIb study, which showed that Tenofovir reduced HIV by 39% (Abdool Karim et al, 2010). This result could not be replicated in a phase III trial (Rees et al, 2015).…”

“…So far, only two products have shown significant results in preventing HIV (Abdool Karim et al, 2010;Baeten et al, 2016;Nel et al, 2016). The first is the CAPRISA 004 Phase IIb study, which showed that Tenofovir reduced HIV by 39% (Abdool Karim et al, 2010).…”

Truvada (emtricitabine/tenofovir) pre-exposure prophylaxis roll-out among South African university students: Lots of positives, but let us keep an eye on possible surprises

“…It is important to note that many studies with Truvada and preventive vaginal gels, involving thousands of women, have failed in SA and other Southern African Development Community countries. [2,3] These studies include trials such as FACTS and VOICE, [4][5][6] and it is thought that failure was due to lack of adherence and not ineffectiveness. The roll-out of Truvada therefore aims to offer protection to students at risk of HIV infection, in the hope that they will have better adherence, and has been extended to HIV-negative students across nine institutions of higher learning across SA.…”

HIV prevention among female sex workers in Africa

“…The successful results in the use of 'treatment as prevention' to prevent HIV among serodiscordant couples may have a role in reducing HIV transmission between sex workers and clients (Baeten & Celum 2011). Pre-exposure prophylaxis in the form of a topical vaginal microbicide has shown promise in the African context, and a successful product could empower sex workers to reduce their vulnerability to HIV (Abdool Karim, Abdool Karim, Frohlich, Grobler, Baxter, Mansoor, et al 2010). In the future, and if supported by evidence, oral pre-exposure prophylaxis may be another prevention option for HIV negative sex workers.…”