On Demand Antiretroviral Pre-exposure Prophylaxis for HIV Infection in Men Who Have Sex With Men (IPERGAY)

May 10, 2017 updated by: ANRS, Emerging Infectious Diseases
This phase III, multi-centre, comparative, double-blind, randomized trial on 2 parallel groups is designed to evaluate a strategy for the prevention of HIV infection including "on demand" antiretroviral pre-exposure with Truvada versus placebo, associated with overall prevention (counselling, condoms, sexually transmitted diseases (STD) screening, hepatitis B virus (HBV) and hepatitis A virus (HAV) vaccinations and post-exposure treatment of HIV infection) in men who have sex with men (MSM), exposed to the risk of HIV infection. Indeed recent studies have reported a higher incidence of new HIV infection in MSM as compared to the general population, new approaches to the prevention of HIV infection are, therefore, necessary in order to consider the limits of current strategies.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The trial has been taken place in two phases in order to ensure the general feasibility of the study:

  • a first enrollment phase for at least 300 participants to ensure the possibility for recruitment in France and Canada and to validate the tools put into place as part of the trial to enroll and follow participants
  • a second phase of 1600 additional participants. This extension phase started on July 2014.

The recruitment has been suspended following the recommendations of Data Safety and Monitoring Board (DSMB): the placebo arm has been stopped and Truvada was available for all the participants of the trial since November 2014. The initial protocol was amended and 361 participants were enrolled in the open-label phase. Sub-studies were proposed to the participants:

  • Sub-study on the outcome of participants receiving sofosbuvir/ledipasvir treatment for recent HCV infection (protocol amendment on April 2015)
  • Randomized sub-study to evaluate the efficacy of doxycycline post-exposure prophylaxis on sexually transmitted infections (protocol amendment on July 2015)
  • Sub-study to evaluate Truvada adherence with Medication Event Monitoring System (MEMS) (protocol amendment on December 2015)
  • Sub-study on drugs use and the impact on sexual behavior and Truvada adherence (protocol amendment on December 2015).

Study Type

Interventional

Enrollment (Actual)

400

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Montréal, Canada
        • CHUM - Hôpital Hôtel Dieu
      • Lyon, France
        • Hopital de la Croix Rousse
      • Nantes, France, 44093
        • Chu Hotel Dieu
      • Nice, France, 06202
        • Hopital de l'Archet
      • Paris, France, 75
        • Hopital Tenon
      • Paris Cedex 10, France, 75475
        • Hôpital Saint-Louis
      • Tourcoing, France, 59208
        • Hôpital Gustave Dron

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Age ≥ 18 years old
  • Male (or transgender) having sex with men
  • Not infected with HIV-1 or HIV-2
  • Elevated risk of HIV contamination : anal sexual relations with at least 2 different sexual partners within the past 6 months without the systematic use of a condom
  • Satisfactory kidney function with a clearance of more than 60 mL/min (Cockcroft formula)
  • Alanine aminotransferase (ALT) < 2.5 Upper Limit of Normal (ULN),
  • Neutrophil granulocytes ≥ 1 000/mm3, haemoglobin ≥ 10 g/dL, platelets ≥ 150 000/mm3
  • Negative HBs antigen and negative hepatitis C virus (HCV) serology (or negative HCV PCR if positive serology)
  • Agrees to be contacted personally, if possible by telephone, short message system (SMS) or e-mail
  • Agrees to the constraints imposed by the trial (visits every 2 months)
  • Subjects enrolled in or a beneficiary of a Social Security program (State Medical Aid or Aide médicale de l'Etat (AME) is not a Social Security program).
  • Signature of the informed consent form.

Exclusion Criteria:

  • Subject in a stable and exclusive relationship with a person
  • Systematic use of a condom during sexual relations
  • Expected to go abroad for more than 3 consecutive months or move expected to a city where the study is not being conducted.
  • Presence of significant glycosuria or proteinuria > 1+ in the urine dipstick, in the absence of infection.
  • Presence of significant haematuria or leukocyturia > 2+ in the urine dipstick, in the absence of infection.
  • History of chronic kidney disease, osteoporosis, osteopaenia
  • History of pathological bone fracture not related to trauma
  • Treatment with Interferon, Interleukin, or antiretrovirals
  • Treatment that could inhibit or compete with the tubular secretion of antiretrovirals
  • Treatment undergoing investigation
  • Intravenous toxicomania
  • Subject who is currently receiving or going to receive a potentially nephrotoxic treatment (long-term anti-inflammatory)
  • Gastro-intestinal disease (or chronic nausea or vomiting) disrupting the absorption of treatments
  • Positive HBs antigen
  • Positive HCV serology with positive HCV PCR
  • Life-threatening disease (lymphoma) or other serious disease (cardiovascular, renal, pulmonary, unstable diabetes) that could require treatment that could disrupt adherence to the treatment
  • Subject potentially non-compliant.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Truvada
associated with an overall offer of prevention (counselling, STD screening, condoms, HAV and HBV vaccinations, treatment post-exposure to the HIV infection)
2 tablets of truvada within 24 hours before first sexual relations, then 1 tablet of Truvada during the period of sexual activity including the last sexual intercourse, finally, a last dose of 1 tablet of Truvada approximately 24 hours later
Other Names:
  • tenofovir disoproxil and emtricitabine
Placebo Comparator: Placebo of Truvada
associated with an overall offer of prevention (counselling, STD screening, condoms, HAV and HBV vaccinations, treatment post-exposure to the HIV infection)
2 tablets of placebo within 24 hours before first sexual relations, then 1 tablet of placebo every 24 hours during the period of sexual activity including the last sexual intercourse, finally, a last dose of 1 tablet of placebo approximatively 24 hours later

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Contamination with HIV-1 or -2
Time Frame: From randomization to the end of the trial. The trial end date will be set by the scientific committee when the necessary number of primary endpoints has been reached without exceeding 5 years of follow-up.
The primary endpoint criteria is contamination with HIV-1 or -2, defined by the first diagnostic proof of infection: positive HIV serum test (using combined latest-generation tests HIV-1 + 2) or a positive test for HIV-1-RNA Polymerase Chain Reaction (PCR) in the plasma.
From randomization to the end of the trial. The trial end date will be set by the scientific committee when the necessary number of primary endpoints has been reached without exceeding 5 years of follow-up.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evolution of sexual behavior and potential at-risk behavior
Time Frame: Every 2 months without exceeding 5 years of follow-up.
Self-questionnaires
Every 2 months without exceeding 5 years of follow-up.
Incidence of clinical and biological adverse events
Time Frame: From randomization to the end of the trial, without exceeding 5 years of follow-up.
From randomization to the end of the trial, without exceeding 5 years of follow-up.
Treatment adherence
Time Frame: Every 2 months without exceeding 5 years of follow-up.
Self-questionnaires, pill count. Drugs levels in plasma and hair (every 4 months).
Every 2 months without exceeding 5 years of follow-up.
Incidence of hepatitis B
Time Frame: From randomization to the end of the trial, without exceeding 5 years of follow-up
From randomization to the end of the trial, without exceeding 5 years of follow-up
Incidence of other sexually transmitted diseases
Time Frame: From randomization to the end of the trial, without exceeding 5 years of follow-up
From randomization to the end of the trial, without exceeding 5 years of follow-up
Frequency of HIV resistance to antiretrovirals in HIV infected subjects
Time Frame: At a visit as soon as the HIV infection is diagnosed
Genotype
At a visit as soon as the HIV infection is diagnosed
Emtricitabine and tenofovir concentrations in plasma, saliva and rectal samples.
Time Frame: 0, 30 min, 1, 2, 4, 8 and 24 hours post-dose (2 tablets of Truvada)
Ancillary study proposed between week-4 and the randomization - 12 volunteers. Blood and saliva samples at all time points and 2 sessions with rectal biopsies at two times for each volunteer (one before the drug is taken and one at one time after taking the 2 tablets)
0, 30 min, 1, 2, 4, 8 and 24 hours post-dose (2 tablets of Truvada)
Costs evaluation
Time Frame: From randomization to the end of the trial, without exceeding 5 years of follow-up.

Modelling to estimate an increase of years of life expectancy and of quality adjusted life year (QALY).

Cost per avoided HIV contamination

From randomization to the end of the trial, without exceeding 5 years of follow-up.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Jean-Michel MOLINA, Professor, Hôpital Saint-Louis Paris FRANCE

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2012

Primary Completion (Actual)

June 30, 2016

Study Completion (Actual)

December 15, 2016

Study Registration Dates

First Submitted

November 8, 2011

First Submitted That Met QC Criteria

November 14, 2011

First Posted (Estimate)

November 17, 2011

Study Record Updates

Last Update Posted (Actual)

May 11, 2017

Last Update Submitted That Met QC Criteria

May 10, 2017

Last Verified

May 1, 2017

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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