Tenofovir-Based Preexposure Prophylaxis for HIV Infection among African Women

Abstract

BACKGROUND Reproductive-age women need effective interventions to prevent the acquisition of human immunodeficiency virus type 1 (HIV-1) infection. METHODS We conducted a randomized, placebo-controlled trial to assess daily treatment with oral tenofovir disoproxil fumarate (TDF), oral tenofovir–emtricitabine (TDF-FTC), or 1% tenofovir (TFV) vaginal gel as preexposure prophylaxis against HIV-1 infection in women in South Africa, Uganda, and Zimbabwe. HIV-1 testing was performed monthly, and plasma TFV levels were assessed quarterly. RESULTS Of 12,320 women who were screened, 5029 were enrolled in the study. The rate of retention in the study was 91% during 5509 person-years of follow-up. A total of 312 HIV-1 infections occurred; the incidence of HIV-1 infection was 5.7 per 100 person-years. In the modified intention-to-treat analysis, the effectiveness was −49.0% with TDF (hazard ratio for infection, 1.49; 95% confidence interval [CI], 0.97 to 2.29), −4.4% with TDF-FTC (hazard ratio, 1.04; 95% CI, 0.73 to 1.49), and 14.5% with TFV gel (hazard ratio, 0.85; 95% CI, 0.61 to 1.21). In a random sample, TFV was detected in 30%, 29%, and 25% of available plasma samples from participants randomly assigned to receive TDF, TDF-FTC, and TFV gel, respectively. Independent predictors of TFV detection included being married, being older than 25 years of age, and being multiparous. Detection of TFV in plasma was negatively associated with characteristics predictive of HIV-1 acquisition. Elevations of serum creatinine levels were seen more frequently among participants randomly assigned to receive oral TDF-FTC than among those assigned to receive oral placebo (1.3% vs. 0.2%, P = 0.004). We observed no significant differences in the frequencies of other adverse events. CONCLUSIONS None of the drug regimens we evaluated reduced the rates of HIV-1 acquisition in an intention-to-treat analysis. Adherence to study drugs was low.

The Vaginal Acquisition and Dissemination of HIV-1 Infection in a Novel Transgenic Mouse Model Is Facilitated by Coinfection with Herpes Simplex Virus 2 and Is Inhibited by Microbicide Treatment

“…Nevertheless, despite adhering to the study regimen, some study subjects still acquired HIV infection. In the VOICE trial, 27% of seroconverters in the vaginal TFV gel treatment group had TFV levels detected in their plasma; in the CAPRISA 004 trial, while high adherers displayed a 54% decrease in HIV-1 acquisition, this group was not completely protected from infection (3,23). These trials support the need to investigate the efficacy of other topical drug formulations with more rapid uptake, increased tissue permeability, and enhanced intracellular concentration or the use of a method for sustained delivery of microbicides, such as an intravaginal ring (29).…”

“…However, a subsequent study of high-risk, predominantly young, unmarried women in sub-Saharan Africa, the Vaginal and Oral Interventions to Control the Epidemic (VOICE) trial, failed to show a protective effect of daily administration of vaginal 1% TFV gel, which, based on analysis of plasma drug levels, was most likely due to low adherence by the study subjects (23). Similarly, the FACTS 001 trial also failed to show any protection, which has also been attributed to poor adherence (24).…”

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.…”

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

“…While questions remain on why some vaginal microbicides have not shown effectiveness in phase III trials (Marrazzo et al, 2015;McCormack et al, 2010;Rees et al, 2015), it is known that there has been less consistent use of the gel in some trials (Marrazzo et al, 2015;Mayer, 2015). Several studies have debated the factors that influence consistent use and generally acceptability of vaginal microbicides (Coly & Gorbach, 2008;Doggett et al, 2015;Domanska & Teitelman, 2012;Mantell et al, 2005;C.…”