Impact of long-acting injectable cabotegravir for HIV pre-exposure prophylaxis persistence and coverage in men who have sex with men in France: a randomized controlled clinical trial.
- Conditions
- HIV prevention
- Interventions
- Registration Number
- 2024-510678-25-00
- Lead Sponsor
- Inserm
- Brief Summary
To compare the sustained PrEP use over time among participants randomized to cabotegravir vs. oral TDF/FTC based PrEP at Month 12.
- Detailed Description
Long-acting injectable cabotegravir (CAB-LA) is a promising agent to address the issue of uptake, adherence, and persistence among oral PrEP users who faced adherence challenges. However, the potential benefits of offering CAB-LA as an additional prevention option for MSM adherent to oral PrEP has yet to be demonstrated. We hypothesize that offering CAB-LA as an additional prevention option for MSM already using oral PrEP can mitigate PrEP fatigue over time, resulting in enhanced PrEP use and increased coverage of at-risk sexual intercourses.
This study is designed as a pragmatic, open-label, multicenter, parallel-group, randomized controlled clinical trial aiming to enroll MSM using PrEP for at least 6 months. Participants will be randomly assigned in a 1:1 ratio to remain on their current oral PrEP regimen with daily and/or on-demand TDF/FTC (Control arm) or to switch to a CAB-LA based PrEP (Intervention arm). Participants will be enrolled over 6 months and followed for two years. The trial will be conducted at 9 clinical sites in the Paris region. The primary objective of the study will be to compare the sustained PrEP use over time among participants randomized to CAB-LA vs. oral TDF/FTC based PrEP at Months 12 and 24. The main secondary objectives will aim to evaluate the PrEP coverage of at-risk sexual intercourses, the change from baseline in sexual risk behaviors, the safety of the drugs, and the HIV incidence.
The study protocol includes three ancillary studies:
* Social science: Focus groups will be conducted among study participants to investigate their perceptions of CAB-LA, motivations for using it, adherence and persistence, changes in HIV risk perception, and impact on sexual satisfaction. Additionally, this study will assess healthcare providers' perceptions, barriers, and facilitators regarding CAB-LA implementation for PrEP.
* Rectal tissue HIV-1 permissibility: This study aims to evaluate the protection from HIV-1 at different time points after oral and injectable CAB initiation using a model of Ex-vivo rectal tissue and PBMCs infection with HIV-1.
* Medico-economics analysis: The main objective of this study is to establish cost-effectiveness performance benchmarks for CAB-LA in HIV PrEP.
Recruitment & Eligibility
- Status
- Ongoing, recruiting
- Sex
- Male
- Target Recruitment
- 322
Age ≥ 18 years.
Cisgender men who have sex with men.
Have taken oral TDF/FTC based PrEP during the past 6 months, either daily or on-demand, with a documented PrEP prescription.
Person affiliated with or a beneficiary of a social security scheme (article L1121-11 of the Public Health Code).
Informed and written consent, signed by the person and the investigator on the day of inclusion, at the latest, and before any examination carried out within the setting of the study (article L1122-1-1 of the Public Health Code).
-
Positive HIV test result at screening or enrollment visit, even if HIV infection is not confirmed.
-
Aspartate aminotransferase (ASAT) or alanine aminotransferase (ALAT) > 5-fold the upper normal limit (UNL).
-
Creatinine clearance lower than 50 mL/min.
-
History of chronic renal disease, osteoporosis or osteopenia.
-
Inflammatory skin conditions which compromise the safety of intramuscular (IM) injections.
-
Known thrombocytopenia or any other known bleeding disorder, which would contraindicate IM injection.
-
Treatment with oral anticoagulant (antiplatelet agents are allowed).
-
Known or suspected allergy to study product components.
-
Surgically placed buttock implants.
-
Planned trip abroad of more than 2 consecutive months or planned move outside the Ile de France region.
-
Individuals who, upon the investigator’s judgement, will not be likely to comply the clinical trial procedures, or with any condition incompatible with study participation.
-
Symptoms and/or clinical signs consistent with an acute HIV infection.
-
Person participating in another research study with an exclusion period still in progress at inclusion. Participants in the ANRS PREVENIR study are authorized to participate in the ANRS CABOPrEP trial.
-
Person under guardianship or curatorship or deprived of liberty by judicial or administrative decision.
-
History of seizure disorder.
-
Ongoing Post-Exposure Prophylaxis (PEP) for HIV.
-
Last titer of hepatitis B surface antibody (anti-HBs) < 10 mIU/mL.
-
Concomitant use of antimycobacterial (rifampin, rifapentine) or enzyme-inducing anticonvulsants (carbamazepine, oxcarbazepine, phenobarbital, phenytoin, etc.).
-
Participants with severe hepatic impairment (Class C) as determined by Child-Pugh classification.
-
Participants having a non-treated chronic HCV infection.
-
Current or chronic history of liver disease or known hepatic or biliary abnormalities.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Oral PrEP with daily or on-demand TDF/FTC Tenofovir disoproxil/Emtricitabine 300mg/200mg fixed-dose combination tablets, for oral use Participants randomly assigned to the oral PrEP regimen will be instructed to take a single dose combination of TDF 300 mg + FTC 200 mg (TDF/FTC), either daily or on-demand, according to their preferences. Long-acting injectable PrEP with cabotegavir Cabotegravir Tablets, for oral use. Participants assigned to the cabotegravir group will initially take a 30mg oral tablet of cabotegravir daily for a four-week period. Following this initial phase, they will receive 13 intramuscular injections of 600mg (3mL) long-acting injectable cabotegravir (CAB-LA) administered every two months after an initial loading dose given one month after the last oral tablet. Oral PrEP with daily or on-demand TDF/FTC Rectal Biopsies Participants randomly assigned to the oral PrEP regimen will be instructed to take a single dose combination of TDF 300 mg + FTC 200 mg (TDF/FTC), either daily or on-demand, according to their preferences. Long-acting injectable PrEP with cabotegavir Cabotegravir Extended-Release Injectable Suspension, for intramuscular use. Participants assigned to the cabotegravir group will initially take a 30mg oral tablet of cabotegravir daily for a four-week period. Following this initial phase, they will receive 13 intramuscular injections of 600mg (3mL) long-acting injectable cabotegravir (CAB-LA) administered every two months after an initial loading dose given one month after the last oral tablet. Long-acting injectable PrEP with cabotegavir Rectal Biopsies Participants assigned to the cabotegravir group will initially take a 30mg oral tablet of cabotegravir daily for a four-week period. Following this initial phase, they will receive 13 intramuscular injections of 600mg (3mL) long-acting injectable cabotegravir (CAB-LA) administered every two months after an initial loading dose given one month after the last oral tablet.
- Primary Outcome Measures
Name Time Method Completion of all protocol visits at Month 12 with a documented PrEP prescription of CAB or TDF/FTC at each study aligned with the randomization arm. Completion of all protocol visits at Month 12 with a documented PrEP prescription of CAB or TDF/FTC at each study aligned with the randomization arm.
- Secondary Outcome Measures
Name Time Method Completion of all protocol visits at Month 24 with a documented PrEP prescription of CAB or TDF/FTC at each study aligned with the randomization arm Completion of all protocol visits at Month 24 with a documented PrEP prescription of CAB or TDF/FTC at each study aligned with the randomization arm
Causes of non-sustained PrEP use over time: missing follow-up visits defined by a visit occurring more than 15 days after the scheduled date, temporary PrEP discontinuation, permanent PrEP discontinuation, switching to another PrEP regimen different from the randomization arm, study discontinuation with PrEP cessation, study discontinuation while maintaining PrEP, and lost to follow-up. Causes of non-sustained PrEP use over time: missing follow-up visits defined by a visit occurring more than 15 days after the scheduled date, temporary PrEP discontinuation, permanent PrEP discontinuation, switching to another PrEP regimen different from the randomization arm, study discontinuation with PrEP cessation, study discontinuation while maintaining PrEP, and lost to follow-up.
PrEP coverage of the last condomless anal sexual intercourse based on self-report at each study visits. This information will be collected in the study eCRF. PrEP coverage of the last condomless anal sexual intercourse based on self-report at each study visits. This information will be collected in the study eCRF.
Satisfaction regarding PrEP regimen measured by a self-administered questionnaire at baseline, 12 and 24 months Satisfaction regarding PrEP regimen measured by a self-administered questionnaire at baseline, 12 and 24 months
Number of sexual partners in the last 3 months evaluated by a self-administered questionnaire before the visits at baseline, 6, 12, 18 and 24 months. Number of sexual partners in the last 3 months evaluated by a self-administered questionnaire before the visits at baseline, 6, 12, 18 and 24 months.
Number of condomless anal sexual intercourse in the month prior each study visits. This information will be collected in the study eCRF. Number of condomless anal sexual intercourse in the month prior each study visits. This information will be collected in the study eCRF.
Occurrence of syphilis, chlamydia, and gonorrhea infections at any time during the study. Occurrence of syphilis, chlamydia, and gonorrhea infections at any time during the study.
Weight, blood pressure, fasting lipid level and HOMA index measured at baseline, 12, and 24 months. Weight, blood pressure, fasting lipid level and HOMA index measured at baseline, 12, and 24 months.
Occurrence of Grade 2 or higher clinical or laboratory drug-related adverse events at any time during the study. Occurrence of Grade 2 or higher clinical or laboratory drug-related adverse events at any time during the study.
Injection site reaction and its severity evaluated by the investigator at each injection visits. Injection site reaction and its severity evaluated by the investigator at each injection visits.
Perception of pain and injection site reactions by participants measured through a self-administrated questionnaire at baseline, 6, 12, 18 and 24 months. Perception of pain and injection site reactions by participants measured through a self-administrated questionnaire at baseline, 6, 12, 18 and 24 months.
PrEP regimen used in the month prior to each study visits (TDF/FTC: daily or on-demand, CAB group: CAB oral or CAB-LA). This information will be collected in the study eCRF. PrEP regimen used in the month prior to each study visits (TDF/FTC: daily or on-demand, CAB group: CAB oral or CAB-LA). This information will be collected in the study eCRF.
Concentration of tenofovir diphosphate (TFV-DP) and emtricitabine triphosphate (FTC-TP) in dried blood spots (DBS) at baseline. Concentration of tenofovir diphosphate (TFV-DP) and emtricitabine triphosphate (FTC-TP) in dried blood spots (DBS) at baseline.
Drugs concentrations in plasma measured at Months 6, 12, 18 and 24: o CAB Group: cabotegravir concentration in plasma. o TDF/FTC group: tenofovir diphosphate (TFV-DP) and emtricitabine triphosphate (FTC-TP) concentration in dried blood spots (DBS). Drugs concentrations in plasma measured at Months 6, 12, 18 and 24: o CAB Group: cabotegravir concentration in plasma. o TDF/FTC group: tenofovir diphosphate (TFV-DP) and emtricitabine triphosphate (FTC-TP) concentration in dried blood spots (DBS).
Study visits occurring “on-time” (At Month 1: ±3 days, other visits: ±7 days). Study visits occurring “on-time” (At Month 1: ±3 days, other visits: ±7 days).
Occurrence of HIV infection at any time during the study, defined as a positive HIV antibody immunoassay (4th generation) confirmed by the presence of HIV ribonucleic acid (RNA). Occurrence of HIV infection at any time during the study, defined as a positive HIV antibody immunoassay (4th generation) confirmed by the presence of HIV ribonucleic acid (RNA).
HIV drug resistance mutations among HIV-infected participants. HIV drug resistance mutations among HIV-infected participants.
Use of psychoactive drugs in the last 3 months evaluated by a self-administered questionnaire before the visits at baseline, 6, 12, 18 and 24 months. Use of psychoactive drugs in the last 3 months evaluated by a self-administered questionnaire before the visits at baseline, 6, 12, 18 and 24 months.
Quality of life measured by the EuroQol-5D questionnaire at baseline, 12 and 24 months. Quality of life measured by the EuroQol-5D questionnaire at baseline, 12 and 24 months.
Mental health measured by the Center for Epidemiologic Studies Depression Scale and the Rosenberg self-esteem scale at baseline, 12 and 24 months. Mental health measured by the Center for Epidemiologic Studies Depression Scale and the Rosenberg self-esteem scale at baseline, 12 and 24 months.
PrEP knowledge score evaluated by a self-administered questionnaire at baseline, 12 and 24 months. PrEP knowledge score evaluated by a self-administered questionnaire at baseline, 12 and 24 months.
Number and nature of uses of community peer support and therapeutic patient education measured through a self-administrated questionnaire at baseline, 6, 12, 18 and 24 months. Number and nature of uses of community peer support and therapeutic patient education measured through a self-administrated questionnaire at baseline, 6, 12, 18 and 24 months.
Trial Locations
- Locations (1)
Assistance Publique Hopitaux De Paris
🇫🇷Paris, France
Assistance Publique Hopitaux De Paris🇫🇷Paris, FranceClaudine DUVIVIERSite contact+33144381742claudine.duvivier@aphp.frLaure SURGERSSite contact+33171970119laure.surgers@aphp.frJean-Paul VIARDSite contact+33142348025jean-paul.viard@aphp.frJade GHOSNSite contact+33140257803jade.ghosn@aphp.frMyriam DIEMERSite contact+33149958037myriam.diemer@aphp.frRomain PALICHSite contact+33142160171romain.palich@aphp.frGilles PIALOUXSite contact+33156017412gilles.pialoux@aphp.frJean-Michel MOLINASite contact+33124499066jean-michel.molina@aphp.fr