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

NCT ID: NCT01772823

Last Updated: 2018-01-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-11-30
• Study Completion Date: 2015-11-30

Brief Summary

Approximately 200 HIV-uninfected young men who have sex with men (YMSM) at high risk of acquiring HIV infection, ages 18-22 years, inclusive, will be recruited across all participating Adolescent Medicine Trials Units (AMTU). The behavioral intervention will be assigned at the level of the site, which include Many Men, Many Voices (3MV) and Personalized Cognitive Counseling (PCC). Subjects will first complete the behavioral intervention offered at their respective site and then be provided with open label emtricitabine (FTC)/tenofovir (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 monitor longer-term outcomes of potential concerns.

Detailed Description

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, measure levels of drug exposure and patterns of risk behavior when YMSM are provided open label FTC/TDF (Truvada®). The study will also examine information regarding safety and efficacy of FTC/TDF (Truvada®) as PrEP from prior studies.

Conditions

HIV Infection

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

3MV Behavioral Intervention Group

3MV Behavioral Intervention combined with open label FTC/TDF (Truvada®) as PrEP

Group Type: EXPERIMENTAL

3MV

Intervention Type: BEHAVIORAL

Many Men, Many Voices (3MV) is based on Social Cognitive Theory and the Transtheoretical Model of Behavior Change. 3MV is a group-level intervention that addresses behavioral and social determinants and other factors influencing the HIV/sexually transmitted infection (STI) risk and protective behaviors of Men having sex with men (MSM) of color. The other factors include cultural, social and religious norms, racial identity and degree of connectedness to communities, HIV/STI interactions, sexual relationship dynamics, and the social influences of racism and homophobia.

Emtricitabine/tenofovir (FTC/TDF (Truvada®))

Intervention Type: DRUG

All subjects will be provided with daily FTC/TDF (Truvada®) as Pre-exposure prophylaxis (PrEP) for 48 weeks.

PCC Behavioral Intervention Group

PCC Behavioral Intervention combined with open label FTC/TDF (Truvada®) as PrEP

Group Type: EXPERIMENTAL

PCC

Intervention Type: BEHAVIORAL

Personalized Cognitive Counseling (PCC) is based on the Model of Relapse Prevention and Gold's Self-Appraisal of Risk Behavior. PCC is a 1-hour, single-session, individual level intervention administered by a trained counselor in a clinic setting. Counselors ask the client to recall and describe in as much detail, a recent encounter of unprotected anal sex with another man of unknown or sero-discordant HIV status. The client then identifies and expresses thoughts, feelings, or attitudes that might have led to the high-risk behavior. The client and counselor examine and identify thoughts that may have led the client to decide to engage in high transmission risk sex. The client and counselor agree on strategies that can be used to deal with similar situations in the future.

Emtricitabine/tenofovir (FTC/TDF (Truvada®))

Intervention Type: DRUG

All subjects will be provided with daily FTC/TDF (Truvada®) as Pre-exposure prophylaxis (PrEP) for 48 weeks.

Interventions

3MV

Many Men, Many Voices (3MV) is based on Social Cognitive Theory and the Transtheoretical Model of Behavior Change. 3MV is a group-level intervention that addresses behavioral and social determinants and other factors influencing the HIV/sexually transmitted infection (STI) risk and protective behaviors of Men having sex with men (MSM) of color. The other factors include cultural, social and religious norms, racial identity and degree of connectedness to communities, HIV/STI interactions, sexual relationship dynamics, and the social influences of racism and homophobia.

Intervention Type: BEHAVIORAL

PCC

Personalized Cognitive Counseling (PCC) is based on the Model of Relapse Prevention and Gold's Self-Appraisal of Risk Behavior. PCC is a 1-hour, single-session, individual level intervention administered by a trained counselor in a clinic setting. Counselors ask the client to recall and describe in as much detail, a recent encounter of unprotected anal sex with another man of unknown or sero-discordant HIV status. The client then identifies and expresses thoughts, feelings, or attitudes that might have led to the high-risk behavior. The client and counselor examine and identify thoughts that may have led the client to decide to engage in high transmission risk sex. The client and counselor agree on strategies that can be used to deal with similar situations in the future.

Intervention Type: BEHAVIORAL

Emtricitabine/tenofovir (FTC/TDF (Truvada®))

All subjects will be provided with daily FTC/TDF (Truvada®) as Pre-exposure prophylaxis (PrEP) for 48 weeks.

Intervention Type: DRUG

Other Intervention Names

Many Men, Many Voices; Personalized Cognitive Counseling; FTC/TDF; Truvada®; Emtricitabine/tenofovir; PrEP

Eligibility Criteria

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 sexually transmitted infection (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 pre-exposure prophylaxis (PrEP);
• Willing to participate in behavioral intervention;
• Reports intention not to relocate out of the Adolescent Medicine Trial Unit (AMTU) study area during the course of the study; and
• Does not have a job or other obligations that would require long absences from the 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 Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) 110 Protocol Team if they are having difficulty making the judgment.);
• History of bone fractures not explained by trauma;
• Acute or chronic hepatitis B infection as indicated by positive hepatitis B surface antigen (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, regardless of urine protein to creatinine ratio(UP/C);
• UP/C > 0.37 g/g at time of screening, regardless of urine dipstick protein result;
• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 22 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

University of North Carolina, Chapel Hill

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sybil Hosek, PhD

Role: STUDY_CHAIR

Cook County Health & Hospitals System

Locations

Children's Hospital of Los Angeles

Los Angeles, California, United States

University of Colorado - The Children's Hospital of Denver

Aurora, Colorado, United States

University of Miami

Miami, Florida, United States

University of South Florida

Tampa, Florida, United States

Stroger Hospital and the CORE Center

Chicago, Illinois, United States

Tulane University

New Orleans, Louisiana, United States

Johns Hopkins University

Baltimore, Maryland, United States

Fenway Institute

Boston, Massachusetts, United States

Wayne State University

Detroit, Michigan, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

St. Jude Childrens Research Hospital

Memphis, Tennessee, United States

Baylor College of Medicine

Houston, Texas, United States

Countries

United States

References

Havens PL, Perumean-Chaney SE, Patki A, Cofield SS, Wilson CM, Liu N, Anderson PL, Landovitz RJ, Kapogiannis BG, Hosek SG, Mulligan K. Changes in Bone Mass After Discontinuation of Preexposure Prophylaxis With Tenofovir Disoproxil Fumarate/Emtricitabine in Young Men Who Have Sex With Men: Extension Phase Results of Adolescent Trials Network Protocols 110 and 113. Clin Infect Dis. 2020 Feb 3;70(4):687-691. doi: 10.1093/cid/ciz486.

Reference Type: DERIVED

PMID: 31179503 (View on PubMed)

Castillo-Mancilla J, Seifert S, Campbell K, Coleman S, McAllister K, Zheng JH, Gardner EM, Liu A, Glidden DV, Grant R, Hosek S, Wilson CM, Bushman LR, MaWhinney S, Anderson PL. Emtricitabine-Triphosphate in Dried Blood Spots as a Marker of Recent Dosing. Antimicrob Agents Chemother. 2016 Oct 21;60(11):6692-6697. doi: 10.1128/AAC.01017-16. Print 2016 Nov.

Reference Type: DERIVED

PMID: 27572401 (View on PubMed)

Related Links

http://www.atnonline.org

ATN website

Other Identifiers

ATN 110 Version 3.0

Identifier Type: -

Identifier Source: org_study_id