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

NCT ID: NCT01327651

Last Updated: 2025-03-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 622 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-08-31
• Study Completion Date: 2014-12-31

Brief Summary

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.

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.

Conditions

HIV Infections

Study Design

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

Study Groups

Daily dosing

Participants will receive oral FTC/TDF daily.

Group Type: ACTIVE_COMPARATOR

Daily dosing

Intervention Type: DRUG

A fixed-dose combination of emtricitabine and tenofovir disoproxil fumarate.

Time-driven dosing

Participants will receive oral FTC/TDF twice weekly with a post-exposure dose.

Group Type: EXPERIMENTAL

Time-driven dosing

Intervention Type: DRUG

TDF/FTC twice weekly with a post-exposure dose

Event-driven dosing

Participants will receive oral FTC/TDF before and after a potential exposure to HIV infection.

Group Type: EXPERIMENTAL

Event-driven dosing

Intervention Type: DRUG

TDF/FTC as needed with a post exposure dose

Interventions

Daily dosing

A fixed-dose combination of emtricitabine and tenofovir disoproxil fumarate.

Intervention Type: DRUG

Time-driven dosing

TDF/FTC twice weekly with a post-exposure dose

Intervention Type: DRUG

Event-driven dosing

TDF/FTC as needed with a post exposure dose

Intervention Type: DRUG

Other Intervention Names

Daily; TDF/FTC; A fixed-dose combination of emtricitabine and tenofovir disoproxil fumarate.; A fixed-dose combination of emtricitabine and tenofovir disoproxil fumarate.

Eligibility 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

• 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

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

HIV Prevention Trials Network

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Robert M. Grant, MD, MPH

Role: STUDY_CHAIR

University of California, San Francisco

Frits van Griensven, PhD, MPH

Role: STUDY_CHAIR

School of Medicine, University of California at San Francisco

Locations

Harlem Prevention Center CRS

New York, New York, United States

Emavundleni CRS

Cape Town, Western Cape, South Africa

Silom Community Clinic CRS

Nonthaburi, , Thailand

Countries

United States; South Africa; Thailand

References

Grant RM, Lama JR, Anderson PL, McMahan V, Liu AY, Vargas L, Goicochea P, Casapia M, Guanira-Carranza JV, Ramirez-Cardich ME, Montoya-Herrera O, Fernandez T, Veloso VG, Buchbinder SP, Chariyalertsak S, Schechter M, Bekker LG, Mayer KH, Kallas EG, Amico KR, Mulligan K, Bushman LR, Hance RJ, Ganoza C, Defechereux P, Postle B, Wang F, McConnell JJ, Zheng JH, Lee J, Rooney JF, Jaffe HS, Martinez AI, Burns DN, Glidden DV; iPrEx Study Team. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. 2010 Dec 30;363(27):2587-99. doi: 10.1056/NEJMoa1011205. Epub 2010 Nov 23.

Reference Type: BACKGROUND

PMID: 21091279 (View on PubMed)

Hughes JP, Williamson BD, Krakauer C, Chau G, Ortiz B, Wakefield J, Hendrix C, Amico KR, Holtz TH, Bekker LG, Grant R. Combining information to estimate adherence in studies of pre-exposure prophylaxis for HIV prevention: Application to HPTN 067. Stat Med. 2022 Mar 15;41(6):1120-1136. doi: 10.1002/sim.9321. Epub 2022 Jan 25.

Reference Type: DERIVED

PMID: 35080038 (View on PubMed)

Holtz TH, Chitwarakorn A, Hughes JP, Curlin ME, Varangrat A, Li M, Amico KR, Mock PA, Grant RM; Thai HPTN 067/ADAPT Study Team. HPTN 067/ADAPT: Correlates of Sex-Related Pre-exposure Prophylaxis Adherence, Thai Men Who Have Sex With Men, and Transgender Women, 2012-2013. J Acquir Immune Defic Syndr. 2019 Oct 1;82(2):e18-e26. doi: 10.1097/QAI.0000000000002131.

Reference Type: DERIVED

PMID: 31490342 (View on PubMed)

Grant RM, Mannheimer S, Hughes JP, Hirsch-Moverman Y, Loquere A, Chitwarakorn A, Curlin ME, Li M, Amico KR, Hendrix CW, Anderson PL, Dye BJ, Marzinke MA, Piwowar-Manning E, McKinstry L, Elharrar V, Stirratt M, Rooney JF, Eshleman SH, McNicholl JM, van Griensven F, Holtz TH. Daily and Nondaily Oral Preexposure Prophylaxis in Men and Transgender Women Who Have Sex With Men: The Human Immunodeficiency Virus Prevention Trials Network 067/ADAPT Study. Clin Infect Dis. 2018 May 17;66(11):1712-1721. doi: 10.1093/cid/cix1086.

Reference Type: DERIVED

PMID: 29420695 (View on PubMed)

Bekker LG, Roux S, Sebastien E, Yola N, Amico KR, Hughes JP, Marzinke MA, Hendrix CW, Anderson PL, Elharrar V, Stirratt M, Rooney JF, Piwowar-Manning E, Eshleman SH, McKinstry L, Li M, Dye BJ, Grant RM; HPTN 067 (ADAPT) study team. Daily and non-daily pre-exposure prophylaxis in African women (HPTN 067/ADAPT Cape Town Trial): a randomised, open-label, phase 2 trial. Lancet HIV. 2018 Feb;5(2):e68-e78. doi: 10.1016/S2352-3018(17)30156-X. Epub 2017 Oct 3.

Reference Type: DERIVED

PMID: 28986029 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Informed Consent Form

View Document

Other Identifiers

10852

Identifier Type: REGISTRY

Identifier Source: secondary_id

HPTN 067 (ADAPT)

Identifier Type: -

Identifier Source: org_study_id