The ADAPT Study: Use of Emtricitabine and Tenofovir Disoproxil Fumarate for Pre-Exposure Prophylaxis (PrEP)

This study is currently recruiting participants.
Verified September 2013 by National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01327651
First received: December 1, 2010
Last updated: September 4, 2013
Last verified: September 2013
  Purpose

Pre-exposure prophylaxis (PrEP) is a method of preventing HIV infection through the use of antiretroviral (ARV) medications before exposure to HIV. This study will examine the feasibility of different methods of dosing for a PrEP regimen. Three methods of delivery will be compared: daily, time-based, and event-based.


Condition Intervention Phase
HIV Infections
Drug: Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: The ADAPT Study: A Phase II, Randomized, Open-Label, Pharmacokinetic and Behavioral Study of the Use of Intermittent Oral Emtricitabine/Tenofovir Disoproxil Fumarate Pre-Exposure Prophylaxis (PrEP) Pre-Exposure Prophylaxis (PrEP)

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Proportion of sexual exposures covered by pre- and post-exposure dosing [ Time Frame: From Week 6 to Week 30 ] [ Designated as safety issue: No ]
  • Minimum total number of pills needed for 100% coverage [ Time Frame: From Week 6 to about Week 30 ] [ Designated as safety issue: No ]
  • Total number of pills used over the follow-up period [ Time Frame: From Week 6 to Week 30 ] [ Designated as safety issue: No ]
  • Self-reported side effect or symptom scores [ Time Frame: From Week 6 to Week 30 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Amount of tenofovir diphosphate (TFV-DP) in peripheral blood mononuclear cells (PBMCs) [ Time Frame: From Week 0 to Week 5 ] [ Designated as safety issue: No ]
  • Listing of adverse events (AEs) by grade, relationship to study product, and arm [ Time Frame: From Week 1 to Week 30 ] [ Designated as safety issue: Yes ]
  • Drug resistance test results and plasma HIV RNA levels among all participants who seroconvert while enrolled in the study [ Time Frame: At Weeks 10, 18, and 30 or at Weeks 14, 22, and 26 (if after HIV diagnosis) ] [ Designated as safety issue: No ]
  • Proportion of participants who self-report acceptability of assigned study arm, as collected on CASI assessment [ Time Frame: At Weeks 6, 18, and 30 ] [ Designated as safety issue: No ]
  • Perceptions of advantages and disadvantages of different regimens as reported by participants and clinical personnel [ Time Frame: After Week 34 (within a 3-month window) ] [ Designated as safety issue: No ]
  • Percentage of adherence and correctly timed adherence, measured by weekly interviews and electronic drug monitoring data [ Time Frame: From Week 6 to Week 30 ] [ Designated as safety issue: No ]
  • Percentage of adherence, based on pill counts [ Time Frame: From Week 6 to Week 30 ] [ Designated as safety issue: No ]
  • Proportion of participants who discontinue all pre-exposure prophylaxis (PrEP) use as assessed by self-report via CASI or weekly interviews [ Time Frame: From Week 6 to Week 30 ] [ Designated as safety issue: No ]
  • Information related to PrEP use, motivation, and behavioral skills as assessed by self-report via CASI [ Time Frame: At Weeks 6, 18, and 30 ] [ Designated as safety issue: No ]
  • Frequency of unprotected sex acts as assessed via CASI [ Time Frame: At Weeks 6, 18, and 30 ] [ Designated as safety issue: No ]
  • Planning for sex as assessed via CASI [ Time Frame: At Weeks 6, 18, and 30 ] [ Designated as safety issue: No ]
  • Results of safer sex planning survey as assessed via CASI [ Time Frame: At Weeks 6, 18, and 30 ] [ Designated as safety issue: No ]
  • Perceived vulnerability as assessed via CASI [ Time Frame: At Weeks 6, 18, and 30 ] [ Designated as safety issue: No ]
  • PrEP optimism as assessed via CASI [ Time Frame: At Weeks 6, 18, and 30 ] [ Designated as safety issue: No ]
  • Demographic factors [ Time Frame: At enrollment ] [ Designated as safety issue: No ]

Estimated Enrollment: 540
Study Start Date: August 2011
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Daily dosing
Participants will receive oral FTC/TDF daily.
Drug: Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF)
A fixed-dose combination of emtricitabine and tenofovir disoproxil fumarate, two nucleoside reverse transcriptase inhibitors.
Other Names:
  • Truvada
  • FTC/TDF
Active Comparator: Time-driven dosing
Participants will receive oral FTC/TDF twice weekly with a post-exposure dose.
Drug: Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF)
A fixed-dose combination of emtricitabine and tenofovir disoproxil fumarate, two nucleoside reverse transcriptase inhibitors.
Other Names:
  • Truvada
  • FTC/TDF
Active Comparator: Event-driven dosing
Participants will receive oral FTC/TDF before and after a potential exposure to HIV infection.
Drug: Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF)
A fixed-dose combination of emtricitabine and tenofovir disoproxil fumarate, two nucleoside reverse transcriptase inhibitors.
Other Names:
  • Truvada
  • FTC/TDF

Detailed Description:

No single strategy for the prevention of HIV has emerged as consistently used and successful, so multiple strategies have been developed. PrEP involves delivering ARV medications to people before they are exposed to HIV, in order to prevent infection. The optimal method of delivering PrEP has not yet been determined. This study will examine the feasibility of delivering PrEP in three methods. Daily dosing involves receiving ARV medications every day; time-driven dosing involves receiving ARV medications twice weekly plus a post-exposure dose; and event-driven dosing involves receiving ARV medications before and after a potential exposure to HIV. The ARV medication that will be used in this study is a combination pill that contains emtricitabine and tenofovir disoproxil fumarate (FTC/TDF). Recent research studies have shown that, if taken consistently, a daily oral dose of FTC/TDF can reduce the risk of HIV infection.

This study will enroll HIV-uninfected men who have sex with men and transgender women (MSM/TGW) and women who have sex with men (WSM). Participation will last 34 weeks. All participants will be given a combination pill that contains FTC/TDF. For the first 5 weeks, all participants will come to the study clinic weekly to receive a single dose of FTC/TDF.

At Week 6, participants will be randomly assigned to one of three groups. In the daily dosing group, participants will take FTC/TDF once a day. In the time-dosing group, participants will take FTC/TDF twice per week and another dose after sexual intercourse (a post-exposure dose). In the event-dosing group, participants will take FTC/TDF before and after sexual intercourse. During this part of the study, participants will be given FTC/TDF to take on their own. Every week, from Week 6 to Week 29, study officials will call to ask questions about how many pills participants have taken and when they have had sexual intercourse. Participants will also complete computer-assisted self-interviews (CASIs).

Study visits will occur at enrollment, once a week for the first 5 weeks, and then once a month until Week 34. Assessment will include recording of medical history, completing an interview about sexual practices and background, and collection of blood, urine, and hair samples. Select study visits will include vaginal practices assessment (including use of lubricants and vaginal cleansing practices), family planning assessments (for women), and sex hormones assessments (for men).

Participants who acquire HIV infection during the study will discontinue study product. These participants will continue to be followed after enrollment at Weeks 4, 6, 10, 14, 18, 22, 26, 30, and every 12 weeks thereafter, as appropriate, until the last study participant completes follow-up at the study site. Participants whose first reactive HIV rapid test is at Week 34 who are later confirmed to be HIV infected will also be followed every 12 weeks after their Week 30 visit until the last study participant completes follow-up at the study site. Participants who acquire HIV infection during the study will undergo select protocol procedures and will receive counseling and referrals for HIV treatment.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Literacy in one of the study languages (Thai, Xhosa, and/or English)
  • Able to provide written informed consent
  • Able to provide weekly telephonic updates
  • Within 70 days of enrollment:

    1. Serum creatinine less than or equal to the upper limit of normal (ULN) and calculated creatinine clearance of at least 70 mL/min by the Cockcroft-Gault formula. More information on this criterion can be found in the protocol.
    2. Serum phosphate greater than or equal to the lower limit of normal (LLN)
    3. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 2 times ULN
    4. Hemoglobin greater than 10 g/dL
    5. Hepatitis B surface antigen (HBsAg)-negative
    6. Willing and able to provide adequate locator information

Inclusion Criteria for MSM/TGW:

  • Male at birth
  • Reporting anal intercourse and/or receptive neovaginal intercourse with at least one man or transgender woman in the past 6 months
  • One or more of the following risk factors for HIV acquisition in the past 6 months according to self-report: sexual intercourse with more than one man or transgender woman; history of an acute sexually transmitted infection (STI); sex in exchange for money, goods, or favors; condomless intercourse (oral, anal, vaginal, or neovaginal) with a partner known to be HIV-infected or of unknown HIV infection status according to self report

Inclusion Criteria for Women Who Have Sex With Men (WSM):

  • Female at birth or self identify as female
  • Not pregnant or breastfeeding
  • Not able to or not intending to become pregnant during the next year
  • If able to become pregnant, self reported use of an effective method of contraception at Enrollment, and intending to use an effective method for the next 34 weeks
  • One or more of the following risk factors for HIV acquisition in the past 6 months according to self report: sexual intercourse with more than one man; history of an acute STI; sex in exchange for money, goods or favors; condomless intercourse (oral, anal, or vaginal) with a partner known to be HIV-infected or of unknown HIV infection status

Exclusion Criteria:

  • Proteinuria 2+ or greater at screening
  • Glucosuria 2+ or greater at screening
  • Serious and active medical or mental illness
  • One or both HIV rapid tests is reactive at screening or enrollment, regardless of subsequent HIV diagnostic test results
  • Signs or symptoms suggestive of acute HIV infection
  • Use of hypoglycemic agents for diabetes or agents with known nephrotoxic potential
  • Use of ARV therapy (e.g., for post-exposure prophylaxis [PEP] or PrEP) in the 90 days prior to study entry
  • Serum phosphate level below site laboratory LLN
  • Current participation (or participation within 3 months of screening) in any HIV prevention study
  • Previous or current participation in the active arm of an HIV vaccine trial
  • Acute or chronic hepatitis B (HBV) infection (refers to chronic active HBV infection evidenced by a positive test for hepatitis B surface antigen (HBsAg)
  • Presence of a psychological or social condition or an addictive disorder that would preclude compliance with the protocol
  • Any other reason or condition that in the opinion of the investigator would interfere with participation, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01327651

Locations
United States, New York
Harlem Prevention Ctr. CRS (El-Sadr CTU) Recruiting
New York, New York, United States, 10027
Contact: Avelino Loquere, R.N., CCRC, C.C.R.P.    1-646-448-0941    al2061@columbia.edu   
South Africa
Emavundleni Desmond Tutu HIV Centre CRS Recruiting
Cape Town, South Africa, 7750
Contact: Avril Masters    27-21-3860053    avril.masters@hiv-research.org.za   
Thailand
Silom Community Clinic CRS Recruiting
Bangkok, Ratchathewi, Thailand, 10500
Contact: Supaporn Chaikummao    66-26342917    SupapornC@th.cdc.gov   
Sponsors and Collaborators
Investigators
Study Chair: Robert M. Grant, MD, MPH University of California, San Francisco
Study Chair: Frits van Griensven, PhD, MPH School of Medicine, University of California at San Francisco
  More Information

Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01327651     History of Changes
Other Study ID Numbers: HPTN 067 (ADAPT), 10852
Study First Received: December 1, 2010
Last Updated: September 4, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Drug Administration Schedule
Nucleoside Reverse Transcriptase Inhibitors
Pharmacokinetics

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Reverse Transcriptase Inhibitors
Tenofovir
Tenofovir disoproxil
Emtricitabine
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on April 14, 2014