The CHAPS Trial: Combined HIV Adolescent PrEP and Prevention

Phase 2

Completed

• Conditions: HIV/AIDS
• Interventions: Drug: Tenofovir

• Registration Number: NCT03986970
• Lead Sponsor: Wits Health Consortium (Pty) Ltd

Brief Summary

To compare the effect of different PrEP drugs (FTC-TDF and FTC-TAF), doses and timing of doses on p24 antigen level in resected foreskin tissue following HIV exposure ex vivo challenge.

Detailed Description

1. Investigate the timing and dose of FTC-TDF and FTC-TAF as oral PrEP and in vitro PEP (applied directly to removed foreskin tissue) required to prevent ex vivo HIV infection in foreskin tissue and blood using the explant model

2. Determine blood, rectal fluid and foreskin tissue concentrations of FTC, TFV, TAF and their active metabolites that are required for ex vivo HIV protection

3. Evaluate inflammation, cellular activation, foreskin mucosal integrity, gene expression and microbiome in foreskin tissue following oral in vivo PrEP and in vitro PEP

4. Evaluate the efficacy of in vitro post exposure dosing with PrEP in protection against ex vivo HIV infection using the explant model

5. To investigate sexual behaviour, PrEP acceptability and feedback on HIV prevention trials implementation

Study Timeline

• Study First Submitted: 2019-06-06
• Study First Submitted QC: 2019-06-11
• Study First Posted: 2019-06-14
• Study Start: 2019-11-11
• Primary Completion: 2021-02-25
• Study Completion: 2021-02-25
• Status Verified: 2021-04
• Last Update Submitted: 2022-07-29
• Last Update Posted: 2022-08-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 72

Inclusion Criteria

Participants must satisfy all the following criteria within 21 days prior to their circumcision visit:

1. Clinically eligible for either forceps guided, or dorsal slit circumcision
2. The ability to understand and sign a written informed consent form by participant (and participant's legal guardian if younger than 18 years) prior to participation in any study procedures and to comply with all trial requirements
3. Male sex at birth
4. Age 13- 24 years
5. Haemoglobin >9g/dL
6. Weight >35Kg
7. Two negative rapid HIV antibody tests results (manufactured by different companies), dating from 21 days or less prior to VMMC
8. Two locator information details (including physical address, telephone contacts, email) for contacting of either patient or their parent

Exclusion Criteria

1. Any significant acute or chronic medical illness and current therapy that in the opinion of the site investigator would preclude receipt either of investigational products, or VMMC
2. Any evidence that participant is not suitable for VMMC

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 4: FTC-TDF	Tenofovir	FTC-TDF two days, 5 hours before circumcision.
Arm 5: FTC-TDF	Tenofovir	FTC-TDF two days, 21 hours before circumcision.
Arm 6: FTC-TAF	Tenofovir	FTC-TAF one day, 5 hours before circumcision.
Arm 3: FTC-TDF	Tenofovir	FTC-TDF one day, 21 hours before circumcision.
Arm 2: FTC-TDF	Tenofovir	FTC-TDF one day, 5 hours before circumcision.
Arm 7: FTC-TAF	Tenofovir	FTC-TAF one day, 21 hours before circumcision.
Arm 8: FTC-TAF	Tenofovir	FTC-TAF two days, 5 hours before circumcision.
Arm 9: FTC-TAF	Tenofovir	FTC-TAF two days, 21 hours before circumcision.

Primary Outcome Measures

Name	Time	Method
HIV Infection free	15 days	We will ascertain the proportion of patients' foreskin tissue that is not infected with HIV 15 days following our ex-vivo HIV challenge. We will use the concentration of p24 antigen (pg/mL) at day15 and also report the slope of the p24 curves from day 3 to 15 (pg/mL per day) and also the AUC day 3 to 15 (pg/mL days).

Secondary Outcome Measures

Name	Time	Method
Blood PrEP Concentrations	1 year	Plasma concentrations (ng/mL) of FTC, TFV, TAF and their active metabolites that are required for ex vivo HIV protection.
Foreskin tissue PrEP concentration	1 year	Foreskin tissue concentrations (ng/mL) of FTC, TFV, TAF and their active metabolites that are required for ex vivo HIV protection
Timing	1 year	The delay between the timing of last dose of FTC-TDF and FTC-TAF as oral PrEP and the timing of circumcision.
Dose	1 year	The efficacy of preventing in-vitro HIV infection by dose of FTC-TDF and FTC-TAF as oral PrEP compared to no intervention
Efficacy of post-exposure PrEP	1 year	The proportion of participants' foreskin tissue that remains HIV infection free in the ex-vivo challenge model when additional doses of PrEP are added to that model.
Rectal Fluid PrEP concentrations	1 year	Rectal fluid concentrations (ng/mL) of FTC, TFV, TAF and their active metabolites that are required for ex vivo HIV protection.

Trial Locations

Locations (1)

The Perinatal HIV Research Unit; 🇿🇦 Johannesburg, Gauteng, South Africa