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Impact of Long-acting Injectable Cabotegravir for HIV PrEP in MSM in France.

Registration Number
NCT06273943
Lead Sponsor
ANRS, Emerging Infectious Diseases
Brief Summary

The purpose of this study is to evaluate if offering long-acting injectable cabotegravir (CAB-LA) as an additional HIV prevention choice among oral PrEP-experienced men who have sex with men (MSM) in France can significantly increase the sustained PrEP use over time and the PrEP coverage of at-risk sexual risk behaviors.

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
NOT_YET_RECRUITING
Sex
Male
Target Recruitment
322
Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Oral PrEP with daily or on-demand TDF/FTCTenofovir disoproxil/Emtricitabine 300mg/200mg fixed-dose combination tablets, for oral useParticipants 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 cabotegavirCabotegravir 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/FTCRectal BiopsiesParticipants 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 cabotegavirCabotegravir 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 cabotegavirRectal BiopsiesParticipants 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
NameTimeMethod
Number of protocol visits completed with a documented PrEP prescription aligned with the randomization arm.At Month 12
Secondary Outcome Measures
NameTimeMethod
Number of condomless anal sexual intercourse in the month prior to each study visit.At each study visits.
Number of participants with Grade 2 or higher clinical or laboratory drug-related adverse events at any time during the study.From Day 1 up to end of study.
Change from baseline in the insulin resistance index (HOMA-IR).At Months 12 and 24.

HOMA-IR : \[fasting glucose (mmol/L) 脳 fasting insulin (渭mol/L)/22.5\]

Number and severity of injection site reaction.After 12 and 24 Months.
Number of participants with missing follow-up visits, temporary PrEP discontinuation, permanent PrEP discontinuation, switching to another PrEP regimen, study discontinuation, lost to follow-up.At 12 and 24 Months.
Number of sexual partners in the last 3 months.At baseline, 6, 12, 18 and 24 months
Mean PrEP satisfaction score based on study arm.At baseline, 6, 12, 18 and 24 months.
Change from baseline in lipidsAt Months 12 and 24.

Fasting total Cholesterol (mmol/L), LDL cholesterol (mmol/L), HDL cholesterol (mmol/L).

Score of quality of life measured by the EuroQol-5D questionnaireAt baseline, 6, 12, 18 and 24 months.

The possible range of scores is 0 to 100%, with the higher scores indicating better outcome.

Number of participants whose last condomless anal sexual intercourse was not covered by PrEP.At each study visits.
Cabotegravir concentration in plasma and tenofovir diphosphate and emtricitabine triphosphate concentration in dried blood spots.At baseline, 6, 12, 18 and 24 months.
Number of participants with new HIV infection.From Day 1 up to end of study.
Depression score assessed with the Center for Epidemiologic Studies Depression Scale (CES-D).At baseline,12, and 24 months.

The possible range of scores is 0 to 60, with the higher scores indicating worse outcome.

Number of protocol visits completed with a documented PrEP prescription aligned with the randomization arm.At Month 24
Number of participants with syphilis, chlamydiae, and/or gonorrhea infection.From Day 1 up to end of study.
Change from baseline in body weight (kg).At Months 12 and 24.
Number of participants who used psychoactive drugs in the last 3 monthsAt baseline, 6, 12, 18 and 24 months.
Number and nature of uses of community peer support and therapeutic patient education.At baseline, 6, 12, 18 and 24 months.
Self-esteem score assessed with the Rosenberg scale.At baseline,12, and 24 months.

The scale ranges from 0 to 30, with the higher score indicating a better outcome.

Trial Locations

Locations (8)

H么pital Lariboisi猫re

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Paris, Ile De France, France

H么pital Saint Louis

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Paris, Ile De France, France

H么pital H么tel Dieu

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Paris, Ile De France, France

H么pital Saint Antoine

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Paris, Ile De France, France

H么pital Bichat

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Paris, Ile De France, France

H么pital Tenon

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Paris, Ile De France, France

H么pital La Piti茅 Salp锚tri猫re

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Paris, Ile De France, France

H么pital Necker

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Paris, Ile De France, France

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