Influences of geo-spatial location on pre-exposure prophylaxis use in South Africa : positioning microbicides for better product uptake.

CAPRISA, 2017.Abstract available in pdf.https://doi.org/10.1080/09540121.2016.124834

Secrecy, empowerment and protection : positioning PrEP in KwaZulu-Natal, South Africa.

CAPRISA, 2017.Abstract available in pdf

Undue inducement : a case study in CAPRISA 008.

CAPRISA, 2017.Abstract available in pdf

Cervicovaginal inflammation facilitates acquisition of less infectious HIV variants.

CAPRISA, 2017.Abstract available in pdf

Genital—systemic chemokine gradients and the risk of HIV acquisition in women.

CAPRISA, 2017.Abstract available in pdf

Vaginal bacteria modify HIV tenofovir microbicide efficacy in African women.

CAPRISA, 2017.Abstract available in pdf

Impact of an adherence intervention on the effectiveness of tenofovir gel in the CAPRISA 004 trial.

CAPRISA, 2014.Abstract not available in pdf

Adherence in the CAPRISA 004 tenofovir gel microbicide trial.

CAPRISA, 2014.High adherence is key to microbicide effectiveness. Here we provide a description of adherence interventions and the adherence rates achieved in the CAPRISA 004 Tenofovir Gel Trial. Adherence support for the before-and-after dosing strategy (BAT 24) was provided at enrolment and at each monthly study visit. This initially comprised individual counselling and was replaced midway by a structured theory-based adherence support program (ASP) based on motivational interviewing. The 889 women were followed for an average of 18 months and attended a total of 17031 monthly visits. On average women reported 5 sex acts and returned 5.9 empty applicators per month. The adherence rate based on applicator count in relation to all reported sex acts was 72.2% compared to the 82.0% self-reported adherence during the last sex act. Adherence support activities, which achieve levels of adherence similar to or better than those achieved by the CAPRISA 004 ASP, will be critical to the success of future microbicide trials

Adherence challenges with drugs for pre-exposure prophylaxis to prevent HIV infection.

Background: There are 34 million people living with human immunodeficiency virus (HIV) worldwide and each year this number increases. Until a vaccine is discovered, the prevention of new HIV infections remains an urgent priority. Several trials studying the use of oral and topical agents for the prevention of HIV infection have already been completed. Adherence has proved to be a major challenge in achieving product efficacy. Aim of the review: To provide the clinical pharmacist with an understanding of the oral pre-exposure prophylaxis (PrEP) and topical microbicide product pipeline whilst emphasizing the critical importance of adherence to these drugs to avert HIV infection. Methods: PubMed/Medline and the web-based clinical trials registry (ClinTrials.gov) were searched using appropriate key words. For the time period 1992–2013—all phase II and phase III safety and effectiveness studies—testing agents for prevention of HIV infection were included in the review. Efficacy estimates, adherence estimates and reported challenges with adherence were extracted. Results: Twenty-four phase II and III clinical trials were found during review. Of these, 20 trials have been completed, and six trials show effectiveness in preventing HIV infection. The majority of the successful trials were to oral PrEP and to date only one microbicide trial of a vaginal antiretroviral microbicide gel has showed effectiveness. Adherence to study product played a major role in trial outcomes and there are several reasons for non-adherence. These include high on-trial pregnancy rates, low trial retention rates, low participant perception of risk, participant characteristics such as age <25 years, single status, migratory partners and trial fatigue. Study product characteristics such as dosage form, dosing interval, as well as associated adverse events may also influence adherence. Conclusion: Moderate to high adherence is critical to demonstrate efficacy of drugs for HIV prevention. For topical agents, intermittent use associated with coitus is more effective than daily use, particularly if sex is infrequent or partners migrant. For oral agents, daily use is effective but the motivation to use the drug and high risk perception is important. In serodiscordant couples, early initiation of highly active antiretroviral therapy in the infected partner affords almost complete protection to the negative partner. Drugs need to be tailored to the population at risk and availability of multiple drug options are important

Safety of tenofovir gel, a vaginal microbicide, in South African women: results of the CAPRISA 004 Trial.

Background: Tenofovir gel, used vaginally before and after coitus, reduced women’s acquisition of HIV by 39%. This is a safety assessment of tenofovir gel, including renal, bone, gastrointestinal, genital and haematological parameters. Methods: In the Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004, a double-blind, randomized placebo-controlled trial, 445 of the 889 eligibly enrolled women were assigned to tenofovir gel. All participants were advised to use the gel vaginally only, with one dose of gel within 12 h before and a second dose as soon as possible after sex, with no more than two doses in 24 h. Clinical and laboratory safety data were collected at monthly and quarterly visits, respectively. Genital assessments were undertaken at enrolment and quarterly thereafter, or as indicated. Results: Women assigned to tenofovir gel were exposed to an average monthly vaginal dose of 240 mg of tenofovir (six applications). In total, six women, three in each group, had mild creatinine elevations, all of which occurred in July/August 2008. The incidence of anaemia was 3.5 and 3.8 per 100 women-years in tenofovir and placebo groups, respectively (P=0.80). Of the six women (four tenofovir and two placebo) experiencing bone fractures, none were associated with abnormal phosphate or calcium values. The proportion of women with diarrhoea was higher in the tenofovir gel group (17% versus 11%; P=0.026). There was no significant increase of any genital adverse event in the tenofovir group. Conclusions: No significant renal, haematological, genital or bone effects were associated with the use of tenofovir gel. Aside from a puzzling increase in diarrhoea, tenofovir gel has an excellent safety profile