An Open Label Demonstration Project and Phase II Safety Study of Pre-Exposure Prophylaxis

• Additional safety data regarding FTC/TDF (Truvada®) use among HIV-uninfected YMSM [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  Change in serum creatinine from baseline, bone mineral density change from baseline, and change in behavioral disinhibition/risk compensation endpoints (e.g., number of sexual partners, number of times engaged in each type of sex act with and without condom, number of partners of each HIV serostatus, alcohol or recreational ldrug use before or during last sexual encounter, exchanged sex for money, drugs, food or a place to stay during last sexual encounter, HIV risk reduction measures taken with last sexual partner)
• Acceptability, patterns of use, rates of adherence and measured levels of drug exposure when YMSM are provided open label FTC/TDF (Truvada®) and information regarding the safety and efficacy of PrEP from prior studies. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

  Acceptability of PrEP as measured by the acceptability assessment that includes questions on usability of PrEP, user-friendliness of the medication regimen, including an assessment of side effects and delivery format, and acceptability of behaviroal intervention sessions.

  Feasibility of PrEP as measured by process indicators (e.g., number of subjects screened, number eligible, number enrolled, and number choosing to take PrEP)

  Medication adherence as measured by number of days of missed medication per total number of days, period of time that a subject's supply of study medication is assumed to be exhausted based on refill dates, and levels of drug exposure as measured by dried blood spot, plasma and PBMC samples.

• Behavioral disinhibition/risk compensation [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  Changes in behavioral disinhibition/risk compensation as measured by number of sexual partners, number of times engaged in each type of sex act with and without condom, number of partners of each HIV serostatus, alcohol or recreational ldrug use before or during last sexual encounter, exchanged sex for money, drugs, food or a place to stay during last sexual encounter, HIV risk reduction measures taken with last sexual partner etc.

• Acceptability and feasibility of two types of efficacious sexual risk reduction interventions as measured by session evaluation (i.e., was session interesting, was it relevant to their life, and did they learn from the session) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
• Acceptability and feasibility of text message reminders as measured by subject rating of the reasons for missing medications on a 4-point Likert scale. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
• Demographic and/or behavioral difference between study groups. Behavioral disinhibition/risk compensation endpoints will be compared. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
• Explore potential demographic and/or behavioral differences between youth who are interested in participating in a PrEP study versus those who are not. Behavioral disinhibition/risk compensation endpoints will be compared. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Approximately 200 HIV-uninfected YMSM at high risk of acquiring HIV infection, ages 18-22 years, inclusive, will be recruited across all participating Adolescent Medicine Trials Units. The type of behavioral intervention will be assigned at the level of the site. Subjects will first complete the behavioral intervention offered at their respective site and then be provided with open label FTC/TDF (Truvada®) as PrEP. Behavioral and biomedical data will be collected at baseline and 0, 4, 8, 12, 24, 36 and 48 weeks. Any subjects who become HIV infected during the course of the study will be discontinued from the study agent and followed for an additional 24 weeks after the study visit at which HIV infection is confirmed. Those subjects who meet specific bone or renal criteria at the Week 48 visit or the 24-Week HIV Seropositive visit will be followed for an additional 48 weeks in the Extension Phase to more closely monitor any potential concerns. The primary objectives of the study are to provide additional safety data regarding FTC/TDF (Truvada®) use as PrEP in YMSM, to examine acceptability, patterns of use, rates of adherence, and measure levels of drug exposure when YMSM are provided open label FTC/TDF (Truvada®) and information regarding safety and efficacy of PrEP from prior studies, and to examine patterns of risk behavior in YMSM who are provided a behavioral intervention and as well as open label FTC/TDF (Truvada®) and information regarding the safety and efficacy of PrEP from prior studies.

• Behavioral: 3MV
• Behavioral: PCC
• Drug: Emtricitabine/tenofovir (FTC/TDF (Truvada®))

• Experimental: 3MV Behavioral Intervention Group
  3MV Behavioral Intervention Group combined with open label FTC/TDF (Truvada®) as PrEP
  Interventions:

  • Behavioral: 3MV
  • Drug: Emtricitabine/tenofovir (FTC/TDF (Truvada®))
• Experimental: PCC Behavioral Intervention Group
  PCC Behavioral Intervention Group combined with open label FTC/TDF (Truvada®) as PrEP
  Interventions:

  • Behavioral: PCC
  • Drug: Emtricitabine/tenofovir (FTC/TDF (Truvada®))

Inclusion Criteria:

• Willing and able to provide written informed consent;
• Male gender at birth;
• Age 18 years and 0 days through 22 years and 364 days, inclusive, at the time of signed informed consent;
• Self reports evidence of high risk for acquiring HIV infection including at least one of the following:

• At least one episode of unprotected anal intercourse with an HIV-infected male partner or a male partner of unknown HIV status during the last 6 months;

  • Anal intercourse with 3 or more male sex partners during the last 6 months;
  • Exchange of money, gifts, shelter, or drugs for anal sex with a male partner during the last 6 months;
  • Sex with a male partner and has had a STI during the last 6 months or at screening;
  • Sexual partner of an HIV-infected man with whom condoms were not consistently used in the last 6 months; or
  • At least one episode of anal intercourse where the condom broke or slipped off during the last 6 months;
• Tests HIV antibody negative at time of screening;
• Willing to provide locator information to study staff;
• Willing to take PrEP;
• Willing to participate in behavioral intervention;
• Reports intention not to relocate out of AMTU study area during the course of the study; and
• Does not have a job or other obligations that would require long absences from AMTU study area (greater than 4 weeks at a time).

Exclusion Criteria:

• Appears visibly distraught or presence of active serious psychiatric symptoms (e.g., active hallucinations, suicidal, homicidal, or exhibiting violent behavior) at the time of consent;
• Intoxicated or under the influence of alcohol or other drugs at the time of consent;
• Any significant uncontrolled, active or chronic disease process that, in the judgment of the site investigator, would make participation in the study inappropriate. (Appropriately managed conditions, like well-controlled diabetes, would not preclude enrollment; the site is encouraged to contact the ATN 110 Protocol Team if they are having difficulty making the judgment.);
• History of bone fractures not explained by trauma;
• Weight > 350 pounds (159 kilograms);
• Acute or chronic hepatitis B infection as indicated by positive hepatitis B sAg test at time of screening;
• Confirmed renal dysfunction (Creatinine Clearance (CrCl) < 75 ml/min, or serum creatinine ≥ upper limit of normal (ULN), or history of renal parenchymal disease or presence of only one kidney at time of screening;
• Confirmed ≥ Grade 2 hypophosphatemia at time of screening;
• Confirmed ≥ Grade 2 hematologic system abnormality (White Blood Count (WBC), Absolute Neutrophil Count (ANC), hemoglobin, or platelets) at time of screening;
• Confirmed ≥ Grade 2 hepatobiliary system abnormality (Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), or bilirubin) at time of screening;
• Confirmed proteinuria as indicated by urine dipstick result ≥ 1+ at time of screening;
• Urine dipstick result of trace OR negative OR unconfirmed ≥ 1+ (i.e., urine dip ≥ 1+ which, on repeat dip does not confirm at > 1+) requires confirmatory testing with urinary protein-creatinine ratio (Up/cr) at time of screening. If Up/cr > 0.37 g/g, then the subject is not eligible;
• Confirmed normoglycemic glucosuria as indicated by urine dipstick result ≥ 1+ in the presence of normal serum glucose (<120 mg/dL) at time of screening;
• A confirmed Grade ≥ 3 toxicity on any screening evaluations;
• Known allergy/sensitivity to the study agent or its components;
• Concurrent participation in an HIV vaccine study or other investigational drug study, including oral or topical PrEP (microbicide) studies;
• Use of disallowed medications ; or
• Inability to understand spoken English.