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

NCT01327651 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: HPTN 067 (ADAPT)10852
• Study Type: interventional
• Target: 622
• Locations: 3 countries
• Sites: 3

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.

Conditions

HIV Infections

Keywords

Drug Administration Schedule; Nucleoside Reverse Transcriptase Inhibitors; Pharmacokinetics

Outcome Measures

Primary Outcomes (4)

• Proportion of Sexual Exposures Covered by Pre- and Post-exposure Dosing

  Coverage will be determined based on the adjusted electronic and self-reported pill-use data. Specifically, a sex act will be considered as "covered" if at least one pill is taken 96 hours prior the sexual activity and at least one additional pill is taken within 24 hours after the sexual activity. If participant only took pill before the sexual activity (within 96 hours), but no pill taken after sexual activity (within 24 hours), then we considered it as pre-exposure covered. likewise, if participant only took pill after sexual activity (within 24 hours), but did not taken pill before sexual activity (within 96 hours), then we considered it as post-exposure covered. If participant did not taken pill before and after sexual activity, then it was considered as not covered. Note that the same pill can be both pre-exposure dose and a post-exposure dose if events are closely spaced. At no time should a participant in the intermittent arm be taking more pills than the daily arm.

  From week 6 (randomization week) to week 30 (end of self-administered dosing)

• The (Minimum) Total Number of Pills Needed for 100% Coverage Over the Follow-up Period (Based on Randomization Arm and Self-reported Sexual History in the Weekly Interviews)

  Below I reported the number of sex acts as reported based on the adjusted electronic and self-reported sexual activity data, also the number of pills needed for 100% coverage. 100% coverage means all sex events (excluding oral sex) are "covered"; Note: sex act is considered as "covered" if at least one pill is taken 96 hours prior the sexual activity and at least one additional pill is taken within 24 hours after the sexual activity (same coverage definition for all three arms)

  From week 6 (randomization week) to week 30 (end of self-administered dosing)

• The Total Pills Actually Used Over the Follow-up Period

  The total pills actually used over the follow-up period was calculated based on the adjusted electronic and self-reported pill-use data. It could be more or less than required by study design

  From week 6 (randomization week) to week 30 (end of self-administered dosing)

• Self-reported Side Effect or Symptom Scores

  The self-reported symptom/side effect scores for common symptoms/side effects including headache, dizziness, cramping, abdominal pain, and flatulence. Collected during clinic visits. All the presented numbers are the percent of visits with each side effects

  From week 6 (randomization week) to week 30 (end of self-administered dosing)

Secondary Outcomes (8)

• Measurement of TFV-DP (Tenofovir Diphosphate) in PBMC (Peripheral Blood Mononuclear Cell)

  week 10, 18 and 30, which is 4 weeks, 12 weeks, and 24 weeks after randomization

• A Listing of Adverse Events (AEs) by Grade, Relationship to Study Product, and Arm

  From week 6 (randomization week) to week 30 (end of self-administered dosing)

• A Listing, by Arm, of Drug Resistance Test Results and Plasma HIV RNA Levels Among All Participants Who Seroconvert While on Study

  From enrollment to week 30 (end of self-administered dosing)

• The Percentage of Correctly Timed Adherence (Number of Pills Taken Within the Recommended Time Frame/Number of Pills Recommended) During 24 Weeks of Follow-up Based on Weekly Interviews and Adjusted EDM (Electronic Drug Monitoring) Data

  From week 6 (randomization week) to week 30 (end of self-administered dosing)

• The Proportion of Participants Who Discontinue All PrEP Use Based on Self-report Via CASI or Weekly Interviews

  From Week 6 to Week 30

Study Arms (3)

Daily dosing

ACTIVE COMPARATOR

Participants will receive oral FTC/TDF daily.

Drug: Daily dosing

Time-driven dosing

EXPERIMENTAL

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

Drug: Time-driven dosing

Event-driven dosing

EXPERIMENTAL

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

Drug: Event-driven dosing

Interventions

Daily dosing DRUG

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

Also known as: Daily, TDF/FTC

Daily dosing

Time-driven dosing DRUG

TDF/FTC twice weekly with a post-exposure dose

Also known as: A fixed-dose combination of emtricitabine and tenofovir disoproxil fumarate.

Time-driven dosing

Event-driven dosing DRUG

TDF/FTC as needed with a post exposure dose

Also known as: A fixed-dose combination of emtricitabine and tenofovir disoproxil fumarate.

Event-driven dosing

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.
• Serum phosphate greater than or equal to the lower limit of normal (LLN)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 2 times ULN
• Hemoglobin greater than 10 g/dL
• Hepatitis B surface antigen (HBsAg)-negative
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• HIV Prevention Trials Network: lead

Study Sites (3)

Harlem Prevention Center CRS

New York, New York, 10027, United States

Location

Emavundleni CRS

Cape Town, Western Cape, 7750, South Africa

Location

Silom Community Clinic CRS

Nonthaburi, 11000, Thailand

Location

Related Publications (5)

• 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.

  PMID: 21091279 BACKGROUND

• 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.

  PMID: 35080038 DERIVED

• 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.

  PMID: 31490342 DERIVED

• 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.

  PMID: 29420695 DERIVED

• 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.

  PMID: 28986029 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Tenofovir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Maoji Li (Statistical Research Associate)
• Organization: Fred Hutchinson Cancer Research Center

mli2@fredhutch.org

2066676035

Study Officials

• 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

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: One arm is daily TDF/FTC. One arm is twice weekly TDF/FTC with a post-exposure dose. One arm is as needed TDF/FTC with a post-exposure dose.

Study Record Dates

• First Submitted: December 1, 2010
• First Posted: April 1, 2011
• Study Start: August 1, 2011
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: March 27, 2025
• Results First Posted: May 12, 2017

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

TH (1); US (1); ZA (1)