The CHAPS Trial: Combined HIV Adolescent PrEP and Prevention

Conditions

HIV/AIDS

Keywords

Pre-exposure prophylaxis

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

Emily L. Webb, Stefan Petkov, Heejin Yun, Laura Else, Limakatso Lebina et al. (20 authors)

Frontiers in Immunology2024-11-06

10.3389/fimmu.2024.1415475

Dose finding study for on-demand HIV pre-exposure prophylaxis for insertive sex in sub-Saharan Africa: results from the CHAPS open label randomised controlled trial.

Herrera C, Serwanga J, Else L, Limakatso L, Opoka D, Ssemata AS, Pillay AD, Namubiru P, Seiphetlo TB, Odoch G, Mugaba S, Seatlholo P, Alieu A, Penchala SD, Muhumuza R, Alinde B, Petkov S, O'Hagan K, Callebaut C, Seeley J, Weiss H, Khoo S, Chiodi F, Gray CM, Kaleebu P, Webb EL, Martinson N, Fox J, CHAPS.

2023-06-142 citations

10.1016/j.ebiom.2023.104648

Mobilization of systemic CCL4 following HIV pre-exposure prophylaxis in young men in Africa

Stefan Petkov, Carolina Herrera, Laura Else, Susan Mugaba, Patricia Namubiru et al. (19 authors)

Frontiers in Immunology2022-07-276 citations

10.3389/fimmu.2022.965214

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.

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.

2020-10-3018 citations

10.1186/s13063-020-04760-x

Interventions

DRUGTenofovir

Pre-exposure prophylaxis

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

NONE

Intervention model description

Open-label, randomised controlled trial (RCT)

Eligibility

Sex/Gender

MALE

Age

13 Years to 24 Years

Healthy volunteers

Yes

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

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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
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.
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.
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
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.

Countries

South Africa

Outcome results

None listed