The CHAPS Trial: Combined HIV Adolescent PrEP and Prevention

Study Overview
=================
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
-----------------
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 Determine blood, rectal fluid and foreskin tissue concentrations of FTC, TFV, TAF and their active metabolites that are required for ex vivo HIV protection Evaluate inflammation, cellular activation, foreskin mucosal integrity, gene expression and microbiome in foreskin tissue following oral in vivo PrEP and in vitro PEP Evaluate the efficacy of in vitro post exposure dosing with PrEP in protection against ex vivo HIV infection using the explant model To investigate sexual behaviour, PrEP acceptability and feedback on HIV prevention trials implementation

Official Title
-----------------
Combined HIV Adolescent PrEP and Prevention: On Demand Pre-exposure Prophylaxis to Provide Protection From HIV in Men - Using Foreskin Tissue to Estimate Protection (Phase II)

Conditions
-----------------
HIV/AIDS

Intervention / Treatment
-----------------
* Drug: Tenofovir


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participants must satisfy all the following criteria within 21 days prior to their circumcision visit: Clinically eligible for either forceps guided, or dorsal slit circumcision 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 Male sex at birth Age 13- 24 years Haemoglobin >9g/dL Weight >35Kg Two negative rapid HIV antibody tests results (manufactured by different companies), dating from 21 days or less prior to VMMC Two locator information details (including physical address, telephone contacts, email) for contacting of either patient or their parent Exclusion Criteria: 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 Any evidence that participant is not suitable for VMMC

Ages Eligible for Study
-----------------
Minimum Age: 13 Years
Maximum Age: 24 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Open-label, randomised controlled trial (RCT)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Arm 1: Control<br>No PrEP. | |
| Experimental: Arm 2: FTC-TDF<br>FTC-TDF one day, 5 hours before circumcision. | Drug: Tenofovir<br>* Pre-exposure prophylaxis<br>* Other names: Emtricitabine, Tenofovir disoproxil, Tenofovir alafenamide;|
| Experimental: Arm 3: FTC-TDF<br>FTC-TDF one day, 21 hours before circumcision. | Drug: Tenofovir<br>* Pre-exposure prophylaxis<br>* Other names: Emtricitabine, Tenofovir disoproxil, Tenofovir alafenamide;|
| Experimental: Arm 4: FTC-TDF<br>FTC-TDF two days, 5 hours before circumcision. | Drug: Tenofovir<br>* Pre-exposure prophylaxis<br>* Other names: Emtricitabine, Tenofovir disoproxil, Tenofovir alafenamide;|
| Experimental: Arm 5: FTC-TDF<br>FTC-TDF two days, 21 hours before circumcision. | Drug: Tenofovir<br>* Pre-exposure prophylaxis<br>* Other names: Emtricitabine, Tenofovir disoproxil, Tenofovir alafenamide;|
| Experimental: Arm 6: FTC-TAF<br>FTC-TAF one day, 5 hours before circumcision. | Drug: Tenofovir<br>* Pre-exposure prophylaxis<br>* Other names: Emtricitabine, Tenofovir disoproxil, Tenofovir alafenamide;|
| Experimental: Arm 7: FTC-TAF<br>FTC-TAF one day, 21 hours before circumcision. | Drug: Tenofovir<br>* Pre-exposure prophylaxis<br>* Other names: Emtricitabine, Tenofovir disoproxil, Tenofovir alafenamide;|
| Experimental: Arm 8: FTC-TAF<br>FTC-TAF two days, 5 hours before circumcision. | Drug: Tenofovir<br>* Pre-exposure prophylaxis<br>* Other names: Emtricitabine, Tenofovir disoproxil, Tenofovir alafenamide;|
| Experimental: Arm 9: FTC-TAF<br>FTC-TAF two days, 21 hours before circumcision. | Drug: Tenofovir<br>* Pre-exposure prophylaxis<br>* Other names: Emtricitabine, Tenofovir disoproxil, Tenofovir alafenamide;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HIV Infection free | 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). | 15 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rectal Fluid PrEP concentrations | Rectal fluid concentrations (ng/mL) of FTC, TFV, TAF and their active metabolites that are required for ex vivo HIV protection. | 1 year | 
| Foreskin tissue PrEP concentration | Foreskin tissue concentrations (ng/mL) of FTC, TFV, TAF and their active metabolites that are required for ex vivo HIV protection | 1 year | 
| Efficacy of post-exposure PrEP | 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. | 1 year | 
| Timing | The delay between the timing of last dose of FTC-TDF and FTC-TAF as oral PrEP and the timing of circumcision. | 1 year | 
| Dose | The efficacy of preventing in-vitro HIV infection by dose of FTC-TDF and FTC-TAF as oral PrEP compared to no intervention | 1 year | 
| Blood PrEP Concentrations | Plasma concentrations (ng/mL) of FTC, TFV, TAF and their active metabolites that are required for ex vivo HIV protection. | 1 year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pre-exposure prophylaxis