The goal of this clinical trial is to offer adolescents and young people in Cape Town, South Africa different HIV pre-exposure prophylaxis (PrEP) products and describe how they use these products over an 18-month period. The study has both clinical and implementation primary aims. The primary clinical aim is short and long-term persistence on PrEP. Persistence is defined as the length of time that a participant shows continuous use of a PrEP product as intended, without stopping PrEP or switching to another PrEP product. The primary implementation aim involves the determination of factors that either enable or serve as a barrier to PrEP uptake and continuation.
Participants will be offered a choice between three antiretroviral-containing PrEP products: (1) a Tenofovir-based oral tablet that needs to be taken daily; (2) a vaginal ring containing Dapivirine that provides HIV protection for up to one month; and (3) an intramuscular injection containing Cabotegravir that provides HIV protection for up to two months. Participants will be able to use the same product throughout the study, switch between products, or stop and restart on PrEP at any point.
The study will be offered from two study sites: the first is a mobile clinic that rotates on a fixed schedule across the study area and the second is a fixed-location government primary healthcare clinic. The study will be open to confirmed HIV-negative individuals, including adolescent girls and young women (aged 15-29 years), young gender and sexually diverse populations aged 15-29 years (including men who have sex with men, transgender people, and non-binary people), and their collective sexual partners (including heterosexual, cisgender men) of any age.
All participants must be HIV negative at baseline
All participants must have a body weight ¬> 35kg at baseline
All participants must be older than 15 years. Specific age criteria will be applied to certain population groups.
All participants must be currently resident in the study area
Confirmed HIV-positive test result and/or signs and symptoms of an acute HIV infection
Clinical conditions contraindicated for the chosen PrEP product as per SAHPRA regulations, including use of known contraindicated medications.
Allergy to any of the study products
Do not spend a reasonable amount of time in the study area as residents, for school, or work, or are otherwise unable to participate in clinical or study visits for geographical reasons, according to the site investigator
Participants will be recruited from the Klipfontein-Mitchells Plain Health sub-district (a peri-urban, high-density, low socio-economic setting) in Cape Town, South Africa. Participants can access the study through the mobile clinic (which rotates through the study area on a fixed schedule) or a local government primary healthcare facility. The target study population includes adolescent girls and young women (aged 15 -29 years) and their intimate male partners (\>15 years). Gender and sexually diverse populations, including men who have sex with men, transgender women, and transgender men, are eligible for study enrollment.
Cohort
Prospective
Cabotegravir long-acting
Drug3ml intramuscular injection containing 600mg of Cabotegravir
Tenofovir emtricitabine
DrugOral tablet taken daily to PrEP HIV infection.
Dapivirine containing vaginal ring
DrugIntra-vaginal silicone ring containing slow-release Dapivirine, replaced every 28 days
Short-term persistence
Persistence (return for PrEP product within a scheduled visit window) over the short-term (7 months) will be measured and reported as persistent vs non-persistent continuation on each specific PrEP product (oral, injectable, ring) and on PrEP overall (accounting for continuation after switching to a different PrEP product). Non-persistence will be defined as failure to return for PrEP within (a) 7 days of the scheduled visit and (b) 28 days of the scheduled visit.
Primary implementation aim.
The combination of implementation strategies best achieve pre-exposure prophylaxis (PrEP) adoption, active implementation (initiation), and persistence (sustainment) outcomes over the short term (7 months) and the long term (18 months) will be collected and reported within a RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework. This will include implementation strategies that describe PrEP choice counselling, the integration of injectable PrEP into standard of care clinical practise, and the differentiating practises required for the effective delivery of PrEP from community based and healthcare facility based settings.
Durable persistence
Persistence (return for PrEP product within a scheduled visit window) over the long-term (18 months) will be measured and reported as persistent vs non-persistent continuation on each specific PrEP product (oral, injectable, ring) and on PrEP overall (accounting for continuation after switching to a different PrEP product). Non-persistence will be defined as failure to return for PrEP within (a) 7 days of the scheduled visit and (b) 28 days of the scheduled visit.
Time on PrEP
Time on PrEP based on expected (e.g. injections given; product collections as logged in dispency records) vs actual (e.g. self-reported patterns of use by the oral and ring PrEP user) PrEP coverage.
Safety of PrEP products
Reported frequency, timing, and nature of self reported and/or clinically identified adverse events (including clinical events, intimate partner violence, and pregnancy and infant outcomes).
Tolerability of PrEP products
Descriptive reports of product tolerability as per the frequency, timing, and nature of self-reported adverse side effect records. Side effects are asked about by HIV counsellors and research nurses at each study visit and rention officers during retention communications.
HIV incidence
HIV incidence (as determined by HIV rapid and laboratory NAAT tests at each study visit and an overview of the medical records of participants lost to follow up and its correlation with individual PrEP use patterns (including PrEP product choice, PrEP persistence, product switching, and/or PrEP pauses and discontinuation over the 18 month study period). This outcome will be reported, however, the sample size of the study is insufficient to allow for a formal analysis of HIV incidence.
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Desmond Tutu HIV Foundation
Lead sponsor
Bill and Melinda Gates Foundation
Collaborator
ViiV Healthcare
Collaborator
