The CHAPS Trial: Combined HIV Adolescent PrEP and Prevention (CHAPS)

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)

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.

Study Overview

• Status: Completed
• Conditions: HIV/AIDS
• Intervention / Treatment: Drug: Tenofovir

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 Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 2

Contacts and Locations

Study Locations

• South Africa
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 1862
      • The Perinatal HIV Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 24 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

9

Arms and Interventions

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

Collaborators and Investigators

• Sponsor: Wits Health Consortium (Pty) Ltd
• Collaborators: London School of Hygiene and Tropical Medicine; King's College London; Karolinska Institutet; Imperial College London; University of Cape Town; University of Liverpool; MRC/UVRI Uganda Research Unit
• Investigators: Principal Investigator: Neil A Martinson, Perinatal HIV Research Unit

Publications and helpful links

General Publications

• Nash S, Dietrich J, Ssemata AS, Herrera C, O'Hagan K, Else L, Chiodi F, Kelly C, Shattock R, Chirenje M, Lebina L, Khoo S, Bekker LG, Weiss HA, Gray C, Stranix-Chibanda L, Kaleebu P, Seeley J, Martinson N, Fox J; CHAPS team. Combined HIV Adolescent Prevention Study (CHAPS): comparison of HIV pre-exposure prophylaxis regimens for adolescents in sub-Saharan Africa-study protocol for a mixed-methods study including a randomised controlled trial. Trials. 2020 Oct 30;21(1):900. doi: 10.1186/s13063-020-04760-x.

Helpful Links

• Related Info
• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2019
• Primary Completion (Actual): February 25, 2021
• Study Completion (Actual): February 25, 2021

Study Registration Dates

• First Submitted: June 6, 2019
• First Submitted That Met QC Criteria: June 11, 2019
• First Posted (Actual): June 14, 2019

Study Record Updates

• Last Update Posted (Actual): August 2, 2022
• Last Update Submitted That Met QC Criteria: July 29, 2022
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Pre-exposure prophylaxis
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir; Emtricitabine
• Other Study ID Numbers: The CHAPS Trial

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: Data will be shared with callaborators.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No