HIV Infections
Conditions
Brief summary
The goal of this hybrid (1a) Cluster Randomised Controlled Trial phase 3B trial is to evaluate the effectiveness and implementation of offering a choice of HIV Pre-Exposure Products (PrEP) through community-based sexual and reproductive health services, on PrEP uptake and retention, and population prevalence of sexually transmissible HIV amongst adolescents and young adults living in rural South Africa. Researchers will compare adding the choice of long-acting PrEP, i.e. two monthly injectable cabotegravir (CAB LA) or dapiravine vaginal ring and HIV post exposure prophylaxis packs to daily oral PrEP integrated with community-based SRH in the 20 intervention clusters with standard of care (SoC), daily oral PrEP integrated with community-based SRH in the 20 control clusters, on uptake and retention on PrEP. We hypothesise that offering a choice of long-acting or oral PrEP and PEP within the community-based delivery of SRH services will overcome the challenges and barriers to effective use of oral daily PrEP and lead to a population-level effect on uptake and retention on PrEP and thus the prevalence of sexually transmissible HIV amongst 15-30 year olds living in rural KwaZulu-Natal, South Africa.
Detailed description
This is a pragmatic trial of adding in a choice of South African Health Products Registration Authority (SAHPRA) approved newer PrEP products - APRETUDE (cabotegravir) 600 mg\\3 mL: DAPIRING (Dapivirine) 25mg Vaginal Ring:56/20.2.8/0979 (22/11/2022) - to the current national department of health approved oral daily PrEP with TVF/FTC (Tenofovir disoproxil/emtricitabine), Objective 1. To measure the effectiveness of the choice of oral and long-acting PrEP, including injectable (CAB LA) and vaginal ring (DapiRing), and post exposure prophylaxis (PEP) on increasing effective uptake (adoption), retention, and adherence of PrEP compared to oral PrEP in young people aged 15-30 in rural South Africa and to estimate the preliminary effect on transmissible HIV and HIV incidence. Objective 2. To understand real-world implementation: 2.1 To explore the acceptability, appropriateness, preference, and reach of CABLA from the perspective of young people aged 15-30 and their communities in rural South Africa 2.2 To understand the feasibility, affordability, and scalability of delivering CABLA through community-based PrEP with SRH. 2.3 To identify implementation challenges and practical solutions for CABLA initiation, laboratory monitoring (e.g. RNA testing), and safe stopping within nurse-led and rural community-based clinical settings 2.4 To evaluate the safety and tolerability of CABLA compared to oral PrEP
Interventions
DRUGAPRETUDE (cabotegravir) 600 mg\3 mL
choice of 2-monthly injectable long acting cabotegravir. The initial visit will be followed by planned visit for the first injection, one month visit for second injection, and then 2-monthly CAB LA injections with repeat HIV testing and pregnancy testing, and referral to peer navigators for adherence and retention support. We will conduct HIV testing, STI testing, Hep B, Hep C, and safety bloods (Full Blood Count, Creatinine, Liver Function Tests) at baseline, HIV testing two monthly, and annual safety bloods, alongside annual STI testing.
DRUGDAPIRING (Dapivirine) 25mg Vaginal Ring
The initial visit is followed by a 7-day phone call, 3-monthly follow-up. Each follow-up will include repeat HIV testing (POCT x2 and dry blood spots for HIV ELISA) and pregnancy testing, syndromic management of STIs, and referral to peer navigators for adherence support and PrEP/ART and if applicable contraception refills. Safely bloods (full blood count, creatinine, liver function tests) will follow national guidelines. Currently we aim to do baseline and annual safety bloods, alongside annual STI testing
The initial visit is followed by a 7-day phone call, 3-monthly follow-up. Each follow-up will include repeat HIV testing (POCT x2 and dry blood spots for HIV ELISA) and pregnancy testing, syndromic management of STIs, and referral to peer navigators for adherence support and PrEP/ART and if applicable contraception refills. Safely bloods (full blood count, creatinine, liver function tests) will follow national guidelines. Currently we aim to do baseline and annual safety bloods, alongside annual STI testing
DRUGTenofovir Disoproxil, Lamuvidine and Dolutegravir
The initial visit is followed by a 7-day phone call, 3-monthly follow-up. Each follow-up will include repeat HIV testing (POCT x2 and dry blood spots for HIV ELISA) and pregnancy testing, syndromic management of STIs, and referral to peer navigators for adherence support and PrEP/ART and if applicable contraception refills. Safely bloods (full blood count, creatinine, liver function tests) will follow national guidelines. Currently we aim to do baseline and annual safety bloods, alongside annual STI testing
Sponsors
Africa Health Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Investigator, Outcomes Assessor)
Masking description
The statistician and clinical team will not participate in the public randomisation. The statistician will remain blinded until the analysis plan has been finalised and the database is locked. Investigators remain blinded to allocation throughout. The participants and intervention delivery teams are not blinded
Intervention model description
A hybrid phase 3B effectiveness implementation type 1a cluster randomised control trial (cRCT)
Eligibility
Sex/Gender
ALL
Age
15 Years to 30 Years
Healthy volunteers
Yes
Inclusion criteria
All young men and women aged 15-30 who are residing in the 40 administrative clusters in the study district and attend any integrated SRH/HIV service Documented HIV negative test Suitable for PrEP and/or already on PrEP Weight \> 35 kg Understand the required dosing schedule and HIV testing. Aware that details can be shared with a peer navigator to support their follow-up If pregnant or breast feeding and/or planning to become pregnant participant can be offered CAB LA, if risk of acquiring HIV out weighs unknown risk of CAB LA, but must understand that safety in pregnancy or breast feeding for CAB LA has not been established and oral daily PrEP is a safe alternative.
Exclusion criteria
History or presence of allergy to the study drugs or their components Investigator assessment find them not suitable Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Retention on PrEP | This will be measured in the clinical cohort of consenting clinic attendeeswho start or are on PrEP/PEP during the first 10 months of the trial. | Defined as attending at least one follow-up appointment after PrEP/PEP initiation, including for HIV testing. |
| Uptake PrEP | This will be evaluated among participants aged 16-30 years in the cross-sectional surveys at 14 months | Defined as the proportion of young people who have taken up any PrEP (oral, injectable, ring, or PEP). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Uptake of risk informed HIV prevention | 14 months | Defined as the proportion of 16-30 year olds who are aware of their HIV status and have undergone a HIV risk assessment to inform HIV prevention and/or are on/start HIV treatment if living with HIV. |
| PrEP Reach (Adoption) | 14 months | Proportion of those at greatest risk adopting (taking up) PrEP or PEP in each arm. Greatest risk is defined as an aggregate exposure disaggregated by gender that includes any of the following factors: out of school (aged \<= 18) or unemployed (aged \>18) and/or engaged in transactional sex or sex work and/or harmful alcohol use (AUDIT scale) and/or experience physical, sexual or emotional violence (validated tool) and/or food poverty (recent experience of hunger) |
| The prevalence of transmissible HIV. | 14 months | We will measure this outcome as the proportion of those living with HIV and have a detectable HIV viral load, defined as having an HIV viral load of \>= 400 copies per ml, during our final survey round. |
| PrEP delivery cost and cost-effectiveness | 14 months | cost per effective PrEP uptake in each arm |
| Adverse events | 14 months | Proportion discontinue or switch due to adverse events in each arm |
| Proportion of men and women aged 16-30 at risk of acquiring HIV or transmitting HIV | 14 months | If living with HIV (a detectable viral load + condomless sex + not on ART), or, if not living with HIV (condomless sex + not on PrEP) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Sexual and reproductive health | 14 months | uptake of family planning, teenage pregnancies and sexually transmitted infection prevalence in each arm |
| Improved socioeconomic outcomes | 14 months | Defined as proportion in school (aged \<= 18) or unemployed (aged \>18) and/or food secure (no recent experience of hunger) in each arm. |
| improved mental health | 14 months | Proportion with PHQ9 score consistent with common mental disorder in each arm |
Countries
South Africa
Contacts
Primary ContactMaryam G Shahmanesh, MBBChir PhD
Backup ContactLimakatso Lebina, MBBS PhD
Outcome results
None listed