Clinical trial NCT03113123: Prevention of HIV in "Île-de-France"
Official title: Prevention of HIV in "Île-de-France"
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: HIV Infections
Keywords: Adherence
Prevention
Tenofovir
Emtricitabine
Antiretroviral
Prophylaxis
Men who have sex with men
Lead sponsor: ANRS, Emerging Infectious Diseases
Sponsor class: OTHER_GOV
First posted: 2017-04-13
Enrollment: 3257
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: Interventional HIV prevention strategy based on pre-exposure prophylaxis (PrEP) with Truvada® for people in the Île-de-France area (or Paris region) who don't have HIV but who are at high risk of becoming infected with HIV (men who have sex with men (MSM), transgender men and women, heterosexual men and women, sex workers, migrants) in combination with overall prevention services (communautary-based or educational counselling; addiction, social and psychological care; condoms and lubricating gel; clean injection equipment; sexually transmitted diseases (STD) screening and treatment; hepatitis A virus (HAV), hepatitis B virus (HBV) and hepatitis C virus (HCV) vaccinations and post-exposure treatment of HIV infection as soon as possible after diagnosis using an antiretroviral combination recommended by the French Guidelines on HIV treatment).

The individual benefit being already demonstrated in clinical trials, the aim is to demonstrate the public health impact of the interventional HIV prevention strategy by reducing the risk of getting HIV-1 infection of at least 15% of new diagnosis of HIV infections among MSM/transgender in the Ile-de-France area after a 3-year period.

Detailed description: Assuming the PrEP efficacy of 80% and that 85% of included participants being MSM - the objective is to evidence a decrease of at least 15% of new diagnosis of HIV infections among MSM in Ile-de-France area. This objective is in the framework of a commitment of large cities against AIDS with the political support of the City of Paris for the "Paris sans SIDA" program and the commitment of the Île-de-France area.

Secondary Objectives:

* Prevalence of HIV infection at the screening visit (undiagnosed epidemic)
* Incidence of HIV infection according to back-calculation approach, and by key subgroups

Operational Objectives:

* Evaluate the origin of the recruitment according to the risk groups and the outreach actions
* Assess linkage to care for PrEP, retention in the study, reasons for consent withdrawal and satisfaction of the participants according to the screening site, the type of PrEP supply, the costs of global care, the key subgroups, the type of counselling, the time from STD testing to initiation of PrEP treatment in study sites
* Impact of a less intense counselling than the one provided in the ANRS IPERGAY trial, on adherence and efficacy of PrEP by comparing the incidence observed in MSM enrolled in the current study to that evidenced in the ANRS IPERGAY trial, with a method similar to that used in the Partner demonstration project in Kenya and Uganda.
* Impact of the communautary-based and educational counselling

Clinical Objectives:

* Estimation, in individuals seeking for PrEP and thus getting tested for HIV infection, the prevalence of HIV infection in different key subgroups, which is a surrogate marker of the undiagnosed (or "hidden") epidemic
* Evaluate who will become HIV-infected during the course of the study while on PrEP, the proportion of patients on combined antiretroviral treatment and the proposition of patients with a suppressed HIV viral load 12 months after HIV infection
* Evaluate the participants' need for post-exposure prophylaxis during the course of the study
* Adherence to PrEP (questionnaire and dried blood spots)
* Assessment of the PrEP dosing schedule used by MSM participants (daily or intermittent) throughout the course of the study
* Assessment of PrEP tolerability and safety
* Comprehensive study of incident HIV infections in those on PrEP (incidence, emergence of drug-associated resistance mutations, adherence to PrEP at the closest visit before HIV seroconversion and at previous visits)

Participants Behavior:

* Acceptability of PrEP (including those who will decline participation in the study) and during the course of the study, and retention in the study.
* Impact of PrEP, within a comprehensive prevention offer, on sexual behavior of the participants throughout follow-up
* Factors associated with the integration of PrEP in the daily routine of participants:

  * Qualitative study to explore the motivations, difficulties, behavior and expectations of the participants, their knowledge and communication on their use of PrEP
  * Reasons related to the choice of the prevention strategy used in terms of dosing schedule (continuous or on demand in MSM) and type of counselling and participation to focus groups.

Care Providers Behavior: Evaluation of knowledge, beliefs, perception and practice of the physicians, nurse and peer counselors involved in delivery of PrEP in the study

Social epidemiology: Evaluation of social and/or territorial inequalities and disparities

Cost-effectiveness of the comprehensive prevention strategy

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years
* Men/transgender men/women who have sex with men, heterosexual men and women, sex workers
* Negative for HIV-1 and HIV-2 (with a fourth generation enzyme-linked immunosorbent assay (ELISA) assay)
* Willing the geocoding of the postal address and to be contacted via telephone or email, on a regular basis
* Willing to comply to visits schedule (every 3 months)
* Health security program
* Informed consent form signed
* High risk of acquiring HIV infection:

  * For MSM and transgenders:

    * Anal sex with at least two different sexual partners and no consistent condom use over the last 6 months
    * And/or history of STD during the last 12 months (syphilis, gonorrhea , chlamydiae, HBV or HCV infection)
    * And/or history of non-occupational post-exposure prophylaxis (PEP) during the last 12 months
    * And/or using psycho-actives drugs during sexual intercourses (cocaine, gammahydroxybutyric acid (GHB), Methylenedioxymethamphetamine (MDMA), mephedrone)
    * And/or having an HIV-infected sexual partner with a detectable plasma viral load (\> 50 copies (cp)/milliliter (ml))
  * For heterosexual:

    * Sexual intercourse with 1 partner originating from regions with high prevalence of HIV infection (\> 1%) (South America, Sub-Saharan Africa, South-East Asia, Eastern Europe, French Guyana) and no consistent condom use
    * and/or sex workers
    * and/or having a sexual partner who is an intravenous drug users sharing injection material
    * and/or having an HIV-infected sexual partner with a detectable plasma viral load (\> 50 cp/ml)

Exclusion Criteria:

* Stable and exclusive relationship with an HIV-negative partner, or with an HIV-positive partner on antiretroviral therapy (ART) with a plasma viral load \< 50 cp/ml
* Positive HIV infection
* Clinical signs of positive HIV infection
* Consistent condom use during sexual intercourse
* Expected trip abroad for 3 consecutive months
* Creatinine clearance lower than 50ml/min
* History of chronic renal disease, osteoporosis or osteopenia
* Receiving an investigational drug
* Receiving or will receive potentially nephrotoxic treatments
* Gastro-intestinal condition that could limit drug absorption
* Potentially non compliant participants
* Breastfeeding
* Hypersensitivity to TDF/FTC
* Positive HBs antigen or isolated anti hepatitis B core (HBc) antibodies if not willing to take daily PrEP
* Severe condition (lymphoma, other cancers, cardio-vascular disease, end-stage renal failure, uncontrolled diabetes)

Primary outcomes:
measure: Reduction of new HIV diagnosis
timeFrame: three years
Secondary outcomes:
measure: Number of recent infections
timeFrame: three years
measure: Prevalence of HIV-infection at the screening visit (undiagnosed epidemic)
timeFrame: two years
measure: Incidence of HIV infection
timeFrame: three years
measure: Retention in the study
timeFrame: two years
measure: Counselling
timeFrame: three years
measure: Type of counselling
timeFrame: three years
measure: Post-exposure prophylaxis
timeFrame: three years
measure: Adherence to PrEP
timeFrame: three years
measure: PrEP dosing schedule
timeFrame: three years
measure: Safety and tolerability
timeFrame: three years
measure: Incident HIV infections
timeFrame: three years
measure: Participants Behavior
timeFrame: three years
measure: Integration of PrEP in the daily routine of participants
timeFrame: three years
measure: Care Providers Behavior
timeFrame: three years
measure: Social epidemiology
timeFrame: three years
measure: Cost-effectiveness
timeFrame: three years
Other outcomes:
Locations:
city: Bobigny
country: France
facility: Hôpital Avicenne
city: Bondy
country: France
facility: Hôpital Jean Verdier
city: Boulogne
country: France
facility: Hôpital Ambroise-Paré
city: Clamart
country: France
facility: Hôpital Antoine Béclère
city: Colombes
country: France
facility: Hôpital Louis Mourier
city: Creteil
country: France
facility: Hôpital Henry Mondor
city: Garches
country: France
facility: Hôpital Raymond Poincaré
city: Le Kremlin Bicêtre
country: France
facility: Hôpital de Bicêtre
city: Melun
country: France
facility: Centre Hospitalier Marc Jacquet
city: Paris
country: France
facility: Hôpital Cochin
city: Paris
country: France
facility: Hôpital Hôtel Dieu
city: Paris
country: France
facility: Hôpital Saint-Louis
city: Paris
country: France
facility: Hôpital Saint-Antoine
city: Paris
country: France
facility: Hôpital Pitié-Salpétrière
city: Paris
country: France
facility: Hôpital Pitié-Salpétrière
city: Paris
country: France
facility: Hôpital Necker-Enfants Malades
city: Paris
country: France
facility: Hôpital Bichat-Claude-Bernard
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou
city: Paris
country: France
facility: Hôpital Tenon
city: Saint Germain en Laye
country: France
facility: CHI Poissy Saint Germain en Laye
city: Suresnes
country: France
facility: Hôpital Foch
city: Versailles
country: France
facility: Hôpital André Mignot
Study officials:
affiliation: Hôpital Saint Louis, Paris, FRANCE
name: Jean-Michel MOLINA, Pr
role: PRINCIPAL_INVESTIGATOR
affiliation: Hôpital Hôtel-Dieu, Paris, FRANCE
name: Jade GHOSN, MD
role: STUDY_CHAIR
References:
citation: Molina JM, Ghosn J, Assoumou L, Delaugerre C, Algarte-Genin M, Pialoux G, Katlama C, Slama L, Liegeon G, Beniguel L, Ohayon M, Mouhim H, Goldwirt L, Spire B, Loze B, Surgers L, Pavie J, Lourenco J, Ben-Mechlia M, Le Mestre S, Rojas-Castro D, Costagliola D; ANRS PREVENIR Study Group. Daily and on-demand HIV pre-exposure prophylaxis with emtricitabine and tenofovir disoproxil (ANRS PREVENIR): a prospective observational cohort study. Lancet HIV. 2022 Aug;9(8):e554-e562. doi: 10.1016/S2352-3018(22)00133-3. Epub 2022 Jun 27.