Emtricitabine/Tenofovir Disoproxil Fumarate for HIV Prevention in Men

NCT00458393 | Completed Phase 3 Results DMC

• 4 other identifiers: CO-US-104-0288104451U01AI064002iPrEx
• Study Type: interventional
• Target: 2,499
• Locations: 6 countries
• Sites: 11

Brief Summary

The purpose of this study is to determine whether daily use of emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) can prevent HIV infection in men who also receive HIV counseling, condoms, and treatment for other sexually transmitted infections (STIs).

Conditions

HIV Infections

Keywords

HIV; Chemoprophylaxis; Hepatitis; Viral human hepatitis; HIV Seronegativity

Outcome Measures

Primary Outcomes (5)

• HIV Seroconversion

  Confirmed HIV infection

  Monthly follow-up through a median of 1.2 years

• Grade 1 or Higher Creatinine Toxicity

  Creatinine which reach grade 1 (mild, 1.1 to 1.3 local upper limit of normal) or higher by the US Division of AIDS grading table (version 1) or a 50% increase in creatinine from the baseline value. The DAIDS table can be found at https://rsc.tech-res.com/docs/default-source/safety/table\_for\_grading\_severity\_of\_adult\_pediatric\_adverse\_events.pdf

  Duration of follow-up, median 1.2 years

• Grade 3 or Higher Phosphorous Toxicity

  Grade 3 or higher phosphorous toxicity (hypophosphatemia) by the Division of AIDS Grading Table (severe, level at or below 1.9 mg/dL)

  The entire follow-up period, median 1.2 years

• Grade 2, 3, or 4 Laboratory Adverse Events

  Number of participants with at least one Grade 2, 3, or 4 laboratory adverse events (moderate, severe of life threatening based one the US Division of AIDS Grading of adverse events, version 1.0). The table can be found at https://rsc.tech-res.com/docs/default-source/safety/table\_for\_grading\_severity\_of\_adult\_pediatric\_adverse\_events.pdf

  Entire follow-up, median 1.2 years

• Grade 2, 3, or 4 Clinical Adverse Events

  Number of participants with at least 1 Grade 2, 3, or 4 clinical adverse events (moderate, severe of life threatening based one the US Division of AIDS Grading of adverse events, version 1.0). The table can be found at https://rsc.tech-res.com/docs/default-source/safety/table\_for\_grading\_severity\_of\_adult\_pediatric\_adverse\_events.pdf

  Entire follow-up, median 1.2 years

Secondary Outcomes (16)

• Hepatitis Flares Among Hepatitis B Virus (HBV) Infected Persons During and After Chemoprophylaxis

  Quarterly lab tests through a median follow-up of 1.2 years

• Percentage Change in Bone Mineral Density

  baseline and week 24.

• Percentage Change in Body Fat

  Baseline and Week 24

• Percentage Change in Fasting Triglycerides

  Baseline and Week 24

• Percent Change in Total Cholesterol

  Baseline and Week 24

Study Arms (2)

TDF/FTC

EXPERIMENTAL

Drug. Daily oral tablet of co-formulated 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate (TDF/FTC).

Drug: daily TDF/FTC

Placebo

PLACEBO COMPARATOR

Drug. Daily oral placebo

Drug: Placebo

Interventions

daily TDF/FTC DRUG

daily oral medication

Also known as: truvada

TDF/FTC

Placebo DRUG

daily oral medication

Placebo

Eligibility Criteria

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

You may qualify if:

• Male sex (at birth)
• HIV uninfected
• Age having reached the local age of consent
• High risk for HIV infection including any of the following: 1) No condom use during anal intercourse with a male HIV-positive partner or a male partner of unknown HIV status during the last 6 months; (2) anal intercourse with more than 3 male sex partners during the last 6 months; (3) exchange of money, gifts, shelter, or drugs for anal sex with a male partner during the last 6 months; (4) sex with a male partner and STI diagnosis during the last 6 months or at screening, or (5) sexual partner of an HIV-infected man with whom condoms are not consistently used in the last 6 months.
• Able to provide a street address of residence for themselves and one personal contact who would know their whereabouts during the study period
• Healthy enough to work, as indicated by score of 80 or greater on the Karnofsky scale
• Certain laboratory values
• A urine dipstick with a negative or trace result for both glucose and protein within 28 days of enrollment.
• Ability to understand and local language for which an informed consent form has been approved by a local IRB and registered with the study sponsor.
• Participated in a randomized, placebo-controlled, PrEP trail
• Has been unblinded
• Has provided informed consent

You may not qualify if:

• Previously diagnosed active and serious infections, including tuberculosis infection, osteomyelitis, or infections requiring parenteral antibiotic therapy
• Active clinically significant medical problems including heart disease (e.g., symptoms of ischemia, congestive heart failure, arrhythmia), lung disease (steroid-dependent chronic obstructive pulmonary disease), diabetes requiring hypoglycemic medication, or previously diagnosed cancer expected to require further treatment
• Acute HBV infection at the screening visit or presence of treatment indications for hepatitis B based on local practice standards; or clinical signs of hepatic cirrhosis
• History of pathological bone fractures not related to trauma
• Receiving ongoing therapy with certain HIV/AIDS-related medications or other medications as determined by the investigator
• Definitely or possibly received an anti-HIV vaccine while participating in a blinded clinical trial
• Current alcohol or drug use that, in the opinion of the investigator, may interfere with the study
• Current participation in a clinical trial or cohort study other than sub-studies of this protocol
• Any condition at enrollment that, in the opinion of the investigator, would make participation in the study unsafe or would interfere with the study
• Sites may utilize additional criteria that restrict enrollment to a subset of people who meet the protocol-defined enrollment criteria.
• \- Site leadership believes participant will have difficulty completing requirements

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Bill and Melinda Gates Foundation: collaborator

Study Sites (11)

San Francisco Dept. of Public Health iPrEx CRS

San Francisco, California, 94102, United States

Location

Stroger Hospital of Cook County/Core Center IPREX CRS

Chicago, Illinois, 60612, United States

Location

Fenway Community Health iPrEx CRS

Boston, Massachusetts, 02215, United States

Location

IPEC/FIOCRUZ iPrEx CRS

Rio de Janeiro, 21040-900, Brazil

Location

Projeto Praca Onze, Universidade Federal do Rio de Janeiro iPrEx CRS

Rio de Janeiro, 21941.590, Brazil

Location

Universidade de Sao Paulo iPrEx CRS

São Paulo, 05403, Brazil

Location

Fundación Ecuatoriana Equidad, Guayaquil, iPrEx CRS

Guayaquil, Guayas, Ecuador

Location

Asociación Civil Selva Amazónica, Iquitos, iPrEx CRS

Iquitos, Maynas, Peru

Location

Investigaciones Médicas en Salud (INMENSA), Lince, iPrEx CRS

Lima, Peru

Location

Desmond Tutu HIV Ctr. iPrEx CRS

Cape Town, 7925, South Africa

Location

Research Institute for Health Sciences iPrEx CRS

Chiang Mai, 50200, Thailand

Location

Related Publications (13)

• 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 RESULT

• Zivich PN, Cole SR, Edwards JK, Glidden DV, Das M, Shook-Sa BE, Shao Y, Mehrotra ML, Adimora AA, Eron JJ. HIV Prevention Among Men Who Have Sex With Men: Tenofovir Alafenamide Combination Preexposure Prophylaxis Versus Placebo. J Infect Dis. 2024 Apr 12;229(4):1123-1130. doi: 10.1093/infdis/jiad507.

  PMID: 37969014 DERIVED

• Mehrotra ML, Westreich D, McMahan VM, Glymour MM, Geng E, Grant RM, Glidden DV. Baseline Characteristics Explain Differences in Effectiveness of Randomization to Daily Oral TDF/FTC PrEP Between Transgender Women and Cisgender Men Who Have Sex With Men in the iPrEx Trial. J Acquir Immune Defic Syndr. 2019 Jul 1;81(3):e94-e98. doi: 10.1097/QAI.0000000000002037. No abstract available.

  PMID: 31192894 DERIVED

• Glidden DV, Mulligan K, McMahan V, Anderson PL, Guanira J, Chariyalertsak S, Buchbinder SP, Bekker LG, Schechter M, Grinsztejn B, Grant RM. Metabolic Effects of Preexposure Prophylaxis With Coformulated Tenofovir Disoproxil Fumarate and Emtricitabine. Clin Infect Dis. 2018 Jul 18;67(3):411-419. doi: 10.1093/cid/ciy083.

  PMID: 29415175 DERIVED

• Glidden DV, Mulligan K, McMahan V, Anderson PL, Guanira J, Chariyalertsak S, Buchbinder SP, Bekker LG, Schechter M, Grinsztejn B, Grant RM. Brief Report: Recovery of Bone Mineral Density After Discontinuation of Tenofovir-Based HIV Pre-exposure Prophylaxis. J Acquir Immune Defic Syndr. 2017 Oct 1;76(2):177-182. doi: 10.1097/QAI.0000000000001475.

  PMID: 28639995 DERIVED

• Gandhi M, Glidden DV, Mayer K, Schechter M, Buchbinder S, Grinsztejn B, Hosek S, Casapia M, Guanira J, Bekker LG, Louie A, Horng H, Benet LZ, Liu A, Grant RM. Association of age, baseline kidney function, and medication exposure with declines in creatinine clearance on pre-exposure prophylaxis: an observational cohort study. Lancet HIV. 2016 Nov;3(11):e521-e528. doi: 10.1016/S2352-3018(16)30153-9. Epub 2016 Aug 31.

  PMID: 27658870 DERIVED

• 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.

  PMID: 27572401 DERIVED

• Glidden DV, Amico KR, Liu AY, Hosek SG, Anderson PL, Buchbinder SP, McMahan V, Mayer KH, David B, Schechter M, Grinsztejn B, Guanira J, Grant RM. Symptoms, Side Effects and Adherence in the iPrEx Open-Label Extension. Clin Infect Dis. 2016 May 1;62(9):1172-7. doi: 10.1093/cid/ciw022. Epub 2016 Jan 20.

  PMID: 26797207 DERIVED

• Mulligan K, Glidden DV, Anderson PL, Liu A, McMahan V, Gonzales P, Ramirez-Cardich ME, Namwongprom S, Chodacki P, de Mendonca LM, Wang F, Lama JR, Chariyalertsak S, Guanira JV, Buchbinder S, Bekker LG, Schechter M, Veloso VG, Grant RM; Preexposure Prophylaxis Initiative Study Team. Effects of Emtricitabine/Tenofovir on Bone Mineral Density in HIV-Negative Persons in a Randomized, Double-Blind, Placebo-Controlled Trial. Clin Infect Dis. 2015 Aug 15;61(4):572-80. doi: 10.1093/cid/civ324. Epub 2015 Apr 23.

  PMID: 25908682 DERIVED

• Liu A, Glidden DV, Anderson PL, Amico KR, McMahan V, Mehrotra M, Lama JR, MacRae J, Hinojosa JC, Montoya O, Veloso VG, Schechter M, Kallas EG, Chariyalerstak S, Bekker LG, Mayer K, Buchbinder S, Grant R; iPrEx Study team. Patterns and correlates of PrEP drug detection among MSM and transgender women in the Global iPrEx Study. J Acquir Immune Defic Syndr. 2014 Dec 15;67(5):528-37. doi: 10.1097/QAI.0000000000000351.

  PMID: 25230290 DERIVED

• Liegler T, Abdel-Mohsen M, Bentley LG, Atchison R, Schmidt T, Javier J, Mehrotra M, Eden C, Glidden DV, McMahan V, Anderson PL, Li P, Wong JK, Buchbinder S, Guanira JV, Grant RM; iPrEx Study Team. HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial. J Infect Dis. 2014 Oct 15;210(8):1217-27. doi: 10.1093/infdis/jiu233. Epub 2014 Apr 16.

  PMID: 24740633 DERIVED

• Buchbinder SP, Glidden DV, Liu AY, McMahan V, Guanira JV, Mayer KH, Goicochea P, Grant RM. HIV pre-exposure prophylaxis in men who have sex with men and transgender women: a secondary analysis of a phase 3 randomised controlled efficacy trial. Lancet Infect Dis. 2014 Jun;14(6):468-75. doi: 10.1016/S1473-3099(14)70025-8. Epub 2014 Mar 7.

  PMID: 24613084 DERIVED

• Amico KR, Mansoor LE, Corneli A, Torjesen K, van der Straten A. Adherence support approaches in biomedical HIV prevention trials: experiences, insights and future directions from four multisite prevention trials. AIDS Behav. 2013 Jul;17(6):2143-55. doi: 10.1007/s10461-013-0429-9.

  PMID: 23435697 DERIVED

MeSH Terms

Conditions

HIV Infections; Hepatitis; Hepatitis, Viral, Human

Interventions

Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

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; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Tenofovir; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: David Glidden
• Organization: University of California, San Francisco

david.glidden@ucsf.edu

415-514-8009

Study Officials

• Robert M. Grant, MD, MPH

  J. David Gladstone Institutes, University of California San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 6, 2007
• First Posted: April 10, 2007
• Study Start: June 1, 2007
• Primary Completion: February 1, 2014
• Study Completion: February 1, 2014
• Last Updated: November 2, 2021
• Results First Posted: January 24, 2018

Record last verified: 2021-10

Locations

TH (1); BR (3); EC (1); US (3); PE (2); ZA (1)