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