Project: CAPRISA 018: A randomised controlled trial to assess the safety, acceptability and pharmacokinetics of a sustained-release tenofovir alafenamide sub-dermal implant for HIV prevention in women

Acronym	CAPRISA 018 (Reference Number: SRIA2015-1061)
Duration	01/01/2017 - 31/12/2022
Project Topic	Ongoing high rates of HIV in young women in Africa remain one of the biggest obstacles to reaching the UNAIDS goal of global HIV epidemic control by 2030. The UNAIDS-Lancet Commission Report identified new technologies for HIV prevention for women as one of the highest priorities in HIV research. While tenofovir has been proven effective for HIV prevention, clinical trials of oral and topical tenofovir-containing pre-exposure prophylaxis (PrEP) have shown inconsistent results in women, mainly due to varying levels of adherence. Unfortunately the monthly dapivirine vaginal ring, designed to improve PrEP adherence, demonstrated only 27% and 31% HIV protection in two recent clinical trials. Alternative, new sustained release formulations are needed to overcome the adherence challenges seen in previous tenofovir trials to achieve high efficacy for HIV prevention in young women in Africa. The high potency and improved safety profile of the tenofovir pro-drug, tenofovir alafenamide (TAF), presents a unique opportunity to develop an innovative sustained-release sub-dermal implant for PrEP. TAF has an established safety profile and has been licensed as part of fixed-dose combination HIV therapy. Besides adherence benefits, sub-dermal implants have the advantage of ease of scale-up since similar contraceptive implants are already routinely available in family planning services in several African countries. Leading PrEP scientists from South Africa, France, Ireland and the United States have formed a consortium to develop and test a novel PrEP formulation, a 6-monthly TAF sub-dermal implant for HIV prevention. The proposed CAPRISA 018 trial aims to primarily assess the safety, acceptability and pharmacokinetics (PK) of the TAF implant, and secondarily to obtain a preliminary estimate of efficacy for HIV prevention in young South African women. The study starts with a lead-in component (Part A) conducted in 40 women over 48 weeks, to assess safety and determine the optimal dose and frequency of implant replacement for the randomized, double-blinded, placebo-controlled trial (Part B) of the TAF implant in 490 at-risk women over 120 weeks. This sample size provides >80% power to detect a five-fold decrease in renal adverse events and a preliminary efficacy estimate of >67%. The CAPRISA 018 trial fast-tracks the TAF implant development timeline and, if positive, provides a clear pathway to a large multi-centre phase III trial. This implant could change the course of the HIV epidemic by offering young women who are unable to negotiate safer sex or adhere to current PrEP regimens, a safe woman-controlled HIV prevention option.
Network	EDCTP2
Call	Research & Innovation Action: Strategic Actions supporting large scale clinical trials

Project partner

Number	Name	Role	Country
1	Centre for the Aids Programme of Research in South Africa	Coordinator	South Africa
2	Stichting Amsterdam Institute for Global Health and Development	Partner	Netherlands
3	Université Jean Monnet, Saint-Etienne	Partner	France