Clinical trial NCT01473472: On Demand Antiretroviral Pre-exposure Prophylaxis for HIV Infection in Men Who Have Sex With Men
Official title: On Demand Antiretroviral Pre-exposure Prophylaxis for HIV Infection in Men Who Have Sex With Men
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infection
Keywords: Prophylaxis
HIV infection
tenofovir
emtricitabine
men who have sex with men
Lead sponsor: ANRS, Emerging Infectious Diseases
Sponsor class: OTHER_GOV
First posted: 2011-11-17
Enrollment: 400
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Contamination with HIV-1 or -2
timeFrame: 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 outcomes:
measure: Evolution of sexual behavior and potential at-risk behavior
timeFrame: Every 2 months without exceeding 5 years of follow-up.
measure: Incidence of clinical and biological adverse events
timeFrame: From randomization to the end of the trial, without exceeding 5 years of follow-up.
measure: Treatment adherence
timeFrame: Every 2 months without exceeding 5 years of follow-up.
measure: Incidence of hepatitis B
timeFrame: From randomization to the end of the trial, without exceeding 5 years of follow-up
measure: Incidence of other sexually transmitted diseases
timeFrame: From randomization to the end of the trial, without exceeding 5 years of follow-up
measure: Frequency of HIV resistance to antiretrovirals in HIV infected subjects
timeFrame: At a visit as soon as the HIV infection is diagnosed
measure: Emtricitabine and tenofovir concentrations in plasma, saliva and rectal samples.
timeFrame: 0, 30 min, 1, 2, 4, 8 and 24 hours post-dose (2 tablets of Truvada)
measure: Costs evaluation
timeFrame: From randomization to the end of the trial, without exceeding 5 years of follow-up.
Other outcomes:
Locations:
city: Montréal
country: Canada
facility: CHUM - Hôpital Hôtel Dieu
city: Lyon
country: France
facility: Hôpital de La Croix Rousse
city: Nantes
country: France
facility: CHU Hôtel Dieu
city: Nice
country: France
facility: Hôpital de l'Archet
city: Paris Cedex 10
country: France
facility: Hôpital Saint-Louis
city: Paris
country: France
facility: Hôpital Tenon
city: Tourcoing
country: France
facility: Hôpital Gustave Dron
Study officials:
affiliation: Hôpital Saint-Louis Paris FRANCE
name: Jean-Michel MOLINA, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Antoni G, Tremblay C, Delaugerre C, Charreau I, Cua E, Rojas Castro D, Raffi F, Chas J, Huleux T, Spire B, Capitant C, Cotte L, Meyer L, Molina JM; ANRS IPERGAY study group. On-demand pre-exposure prophylaxis with tenofovir disoproxil fumarate plus emtricitabine among men who have sex with men with less frequent sexual intercourse: a post-hoc analysis of the ANRS IPERGAY trial. Lancet HIV. 2020 Feb;7(2):e113-e120. doi: 10.1016/S2352-3018(19)30341-8. Epub 2019 Nov 26.
citation: Molina JM, Charreau I, Chidiac C, Pialoux G, Cua E, Delaugerre C, Capitant C, Rojas-Castro D, Fonsart J, Bercot B, Bebear C, Cotte L, Robineau O, Raffi F, Charbonneau P, Aslan A, Chas J, Niedbalski L, Spire B, Sagaon-Teyssier L, Carette D, Mestre SL, Dore V, Meyer L; ANRS IPERGAY Study Group. Post-exposure prophylaxis with doxycycline to prevent sexually transmitted infections in men who have sex with men: an open-label randomised substudy of the ANRS IPERGAY trial. Lancet Infect Dis. 2018 Mar;18(3):308-317. doi: 10.1016/S1473-3099(17)30725-9. Epub 2017 Dec 8.
citation: Molina JM, Charreau I, Spire B, Cotte L, Chas J, Capitant C, Tremblay C, Rojas-Castro D, Cua E, Pasquet A, Bernaud C, Pintado C, Delaugerre C, Sagaon-Teyssier L, Mestre SL, Chidiac C, Pialoux G, Ponscarme D, Fonsart J, Thompson D, Wainberg MA, Dore V, Meyer L; ANRS IPERGAY Study Group. Efficacy, safety, and effect on sexual behaviour of on-demand pre-exposure prophylaxis for HIV in men who have sex with men: an observational cohort study. Lancet HIV. 2017 Sep;4(9):e402-e410. doi: 10.1016/S2352-3018(17)30089-9. Epub 2017 Jul 23.
citation: Molina JM, Capitant C, Spire B, Pialoux G, Cotte L, Charreau I, Tremblay C, Le Gall JM, Cua E, Pasquet A, Raffi F, Pintado C, Chidiac C, Chas J, Charbonneau P, Delaugerre C, Suzan-Monti M, Loze B, Fonsart J, Peytavin G, Cheret A, Timsit J, Girard G, Lorente N, Preau M, Rooney JF, Wainberg MA, Thompson D, Rozenbaum W, Dore V, Marchand L, Simon MC, Etien N, Aboulker JP, Meyer L, Delfraissy JF; ANRS IPERGAY Study Group. On-Demand Preexposure Prophylaxis in Men at High Risk for HIV-1 Infection. N Engl J Med. 2015 Dec 3;373(23):2237-46. doi: 10.1056/NEJMoa1506273. Epub 2015 Dec 1.