Evaluating the Safety and Tolerability of Antiretroviral Drug Regimens Used as Pre-Exposure Prophylaxis to Prevent HIV Infection in At-Risk Men Who Have Sex With Men and in At-Risk Women

NCT01505114 | Completed Phase 2 Results

• 5 other identifiers: HPTN 069/A5305 (NEXT Prep)11789HPTN 069/A5305HPTN 069HPTN 069/NEXT Prep
• Study Type: interventional
• Target: 594
• Locations: 2 countries
• Sites: 13

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 evaluate the safety and tolerability of four ARV regimens in preventing HIV infection in men who have sex with men who may be at risk of getting HIV infection through sex and women who may be at risk of getting HIV infection through sex. The four ARV regimens being evaluated are maraviroc (MVC), MVC plus emtricitabine (FTC), MVC plus tenofovir disoproxil fumarate (TDF), and TDF plus FTC. The MVC-containing arms will be compared to TDF/FTC alone and in combination.

Conditions

HIV Infection

Keywords

HIV Prevention; PrEP; Maraviroc

Outcome Measures

Primary Outcomes (1)

• Occurrence of Grade 3 or Higher Adverse Events (AEs)

  participants had Occurrence of Grade 3 or higher adverse events (AEs)

  Through Week 48

Study Arms (4)

Arm 1

EXPERIMENTAL

MVC 300 mg plus FTC placebo and TDF placebo orally once daily

Drug: Maraviroc; Other: Emtricitabine placebo; Other: Tenofovir disoproxil fumarate placebo

Arm 2

EXPERIMENTAL

MVC 300 mg plus FTC 200 mg and TDF placebo orally once daily

Drug: Maraviroc; Drug: Emtricitabine; Other: Tenofovir disoproxil fumarate placebo

Arm 3

EXPERIMENTAL

MVC 300 mg plus FTC placebo and TDF 300 mg orally once daily

Drug: Maraviroc; Drug: Tenofovir disoproxil fumarate; Other: Emtricitabine placebo

Arm 4

EXPERIMENTAL

MVC placebo plus FTC 200 mg and TDF 300 mg orally once daily

Drug: Emtricitabine; Drug: Tenofovir disoproxil fumarate; Other: Maraviroc placebo

Interventions

Maraviroc DRUG

300-mg tablet, once daily, from Week 0 through Week 48

Also known as: Selzentry, MVC

Arm 1; Arm 2; Arm 3

Emtricitabine DRUG

200-mg capsule, once daily, from Week 0 through Week 48

Also known as: Emtriva, FTC

Arm 2; Arm 4

Tenofovir disoproxil fumarate DRUG

300-mg tablet, once daily, from Week 0 through Week 48

Also known as: Viread, TDF

Arm 3; Arm 4

Maraviroc placebo OTHER

Once daily from Week 0 through Week 48

Arm 4

Emtricitabine placebo OTHER

Once daily from Week 0 through Week 48

Arm 1; Arm 3

Tenofovir disoproxil fumarate placebo OTHER

Once daily from Week 0 through Week 48

Arm 1; Arm 2

Eligibility Criteria

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

You may qualify if:

• For participants in the men's component of the study, born male. For participants in the women's component of the study, born female.
• years or older at the time of screening
• Willing to provide informed consent for the study
• Able to read at a level required for the study components (e.g., computer-assisted self-interview \[CASI\] and short message service \[SMS\], per the judgment of the study investigator)
• For men, a history of receptive or insertive anal intercourse without use of condoms with at least one HIV-infected male partner or male partner of unknown HIV serostatus within 90 days of study entry (provided by self-report)
• For women, a history of vaginal intercourse or receptive anal intercourse without use of condoms with at least one HIV-infected male partner or male partner of unknown HIV serostatus within 90 days of study entry (provided by self-report)
• The following laboratory values must be from specimens obtained within 45 days prior to study enrollment: Nonreactive HIV test results (more information on this criterion can be found in the protocol); hemoglobin (men) greater than 11 g/dL; hemoglobin (women) greater than or equal to 10.5 g/dL; absolute neutrophil count greater than 750 cells/mm\^3; platelet count greater than or equal to 100,000/mm\^3; for men and women, calculated creatinine clearance greater than or equal to 70 mL/minute using the Cockcroft-Gault equation; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than 3 times the upper limit of normal (ULN); total bilirubin less than 2.5 ULN; urine protein less than 2+; and hepatitis B surface antigen (HBsAg) negative.
• No alcohol or substance use that, in the opinion of the study investigator, would interfere with the conduct of the study (e.g., provided by self-report or found upon medical history and examination or in available medical records)
• No medical condition that, in the opinion of the study investigator, would interfere with the conduct of the study (e.g., provided by self-report or found upon medical history and examination or in available medical records)
• Willing to undergo all required study procedures (including sexual assessment by CASI, use of the drug monitoring device, and SMS \[i.e., texting\])
• For all women participants: If of reproductive potential (defined as girls who have reached menarche and pre-menopausal women who have not had a sterilization procedure per self-report (e.g., hysterectomy, bilateral oophorectomy, tubal ligation or salpingectomy), must have a negative serum or urine pregnancy test performed within 48 hours before initiating the protocol-specified medication(s). More information on this criterion can be found in the protocol.
• For all women participants: If participating in sexual activity that could lead to pregnancy, must agree to use a form of contraception from the following list during the trial and for 30 days after stopping the study medication: condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide, IUD, or hormone-base contraceptive.
• For men and women participating in the rectal component, willing to abstain from receptive anal intercourse and practices involving insertion of anything in the rectum (drug, enema, penis, or sex toy) for 3 days prior to rectal biopsy and for 7 days post-biopsy, to minimize risk of HIV-1 infection and bleeding complications after each procedure
• For women participating in the vaginal component, willing to abstain from vaginal intercourse and practices involving insertion of anything in the vagina (drug, douche, penis, or sex toy) for 3 days prior to cervical biopsy and for 7 days post-biopsy, to minimize risk of HIV-1 infection and bleeding complications after each procedure
• For women only, per participant report at screening, usual menstrual cycle with at least 21 days between menses (does not apply to participants who report using a progestin-only method of contraception at screening, e.g., Depo-Provera)

You may not qualify if:

• One or more reactive HIV test results at screening or enrollment, even if HIV infection is not confirmed
• Coenrollment in any other HIV interventional research study (provided by self-report or other available documentation) or prior enrollment and receipt of active arm (i.e., NOT a placebo) of an HIV vaccine trial (provided by available documentation)
• Use of ARV therapy (e.g., for post-exposure prophylaxis \[PEP\] or PrEP) in the 90 days prior to study entry
• Prior history of a gastrectomy, colostomy, ileostomy, or any other procedure altering the gastrointestinal tract or drug absorption (provided by self-report or obtained from medical history or records)
• Receipt of prohibited medications as described in the study drug package inserts or listed in the Study-Specific Populations (SSP) Manual (provided by self-report or obtained from medical history or medical records)
• Ongoing intravenous drug use: episodic use or any use in the past 90 days (as assessed by the study investigator)
• Known medical history of allergy to soy (soya or soybeans) or peanuts
• Weight exceeding 300 pounds (exceeds weight limit of DXA scanners)
• For women, pregnancy or currently breastfeeding
• For Men and Women:
• The following applies to men, and only to women who opt for rectal sampling: Abnormalities of the colorectal mucosa or significant colorectal symptom(s), which in the opinion of the study investigator represent a contraindication to biopsy (including but not limited to presence of any unresolved injury, infectious or inflammatory condition of the local mucosa, and presence of symptomatic external hemorrhoids)
• Per participant report at screening, anticipated use and/or unwillingness to abstain from the following medications during the period of study participation: Heparin, including Lovenox®, Warfarin, Plavix® (clopidogrel bisulfate), or any other drugs that are associated with increased risk of bleeding following biopsy procedures in the opinion of the study investigator
• The following applies to men, and only to women who opt for rectal sampling: Per participant report at screening, anticipated use and/or unwillingness to abstain from rectally administered medications (including over-the-counter products) for 3 days prior to rectal biopsies and for 7 days after biopsies
• Per participant report at screening, anticipated use and/or unwillingness to abstain from the following medications for a period of 10 days before a biopsy procedure: aspirin (daily use of low-dose aspirin \[no more than 81 mg\] is allowed at the discretion of the Investigator of Record) or non-steroidal anti-inflammatory drugs (NSAIDS)
• Abnormal laboratory results for coagulation tests that may indicate an increased risk of bleeding (in the opinion of the investigators)

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• HIV Prevention Trials Network: collaborator
• Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections: collaborator

Study Sites (13)

UCLA CARE Center CRS

Los Angeles, California, 90035, United States

Location

Bridge HIV CRS

San Francisco, California, 94143, United States

Location

George Washington Univ. CRS

Washington D.C., District of Columbia, 20006, United States

Location

Johns Hopkins University CRS

Baltimore, Maryland, 21205, United States

Location

Fenway Health (FH) CRS

Boston, Massachusetts, 02215-4302, United States

Location

New Jersey Medical School Clinical Research Center CRS

Newark, New Jersey, 07103, United States

Location

Weill Cornell Chelsea CRS

New York, New York, 10010, United States

Location

Chapel Hill CRS

Chapel Hill, North Carolina, 27599, United States

Location

Case Clinical Research Site

Cleveland, Ohio, 44106, United States

Location

Penn Therapeutics, CRS

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh CRS

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Washington AIDS CRS

Seattle, Washington, 98104-9929, United States

Location

Puerto Rico AIDS Clinical Trials Unit CRS

San Juan, 00935, Puerto Rico

Location

Related Publications (5)

• Brown KC, Patterson KB, Malone SA, Shaheen NJ, Prince HM, Dumond JB, Spacek MB, Heidt PE, Cohen MS, Kashuba AD. Single and multiple dose pharmacokinetics of maraviroc in saliva, semen, and rectal tissue of healthy HIV-negative men. J Infect Dis. 2011 May 15;203(10):1484-90. doi: 10.1093/infdis/jir059.

  PMID: 21502084 BACKGROUND

• 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

• Kapadia SN, Wu C, Mayer KH, Wilkin TJ, Amico KR, Landovitz RJ, Andrade A, Chen YQ, Chege W, McCauley M, Gulick RM, Schackman BR. No change in health-related quality of life for at-risk U.S. women and men starting HIV pre-exposure prophylaxis (PrEP): Findings from HPTN 069/ACTG A5305. PLoS One. 2018 Dec 26;13(12):e0206577. doi: 10.1371/journal.pone.0206577. eCollection 2018.

  PMID: 30586364 DERIVED

• Gulick RM, Wilkin TJ, Chen YQ, Landovitz RJ, Amico KR, Young AM, Richardson P, Marzinke MA, Hendrix CW, Eshleman SH, McGowan I, Cottle LM, Andrade A, Marcus C, Klingman KL, Chege W, Rinehart AR, Rooney JF, Andrew P, Salata RA, Siegel M, Manabe YC, Frank I, Ho K, Santana J, Stekler JD, Swaminathan S, McCauley M, Hodder S, Mayer KH. Safety and Tolerability of Maraviroc-Containing Regimens to Prevent HIV Infection in Women: A Phase 2 Randomized Trial. Ann Intern Med. 2017 Sep 19;167(6):384-393. doi: 10.7326/M17-0520. Epub 2017 Aug 22.

  PMID: 28828489 DERIVED

• Gulick RM, Wilkin TJ, Chen YQ, Landovitz RJ, Amico KR, Young AM, Richardson P, Marzinke MA, Hendrix CW, Eshleman SH, McGowan I, Cottle LM, Andrade A, Marcus C, Klingman KL, Chege W, Rinehart AR, Rooney JF, Andrew P, Salata RA, Magnus M, Farley JE, Liu A, Frank I, Ho K, Santana J, Stekler JD, McCauley M, Mayer KH. Phase 2 Study of the Safety and Tolerability of Maraviroc-Containing Regimens to Prevent HIV Infection in Men Who Have Sex With Men (HPTN 069/ACTG A5305). J Infect Dis. 2017 Jan 15;215(2):238-246. doi: 10.1093/infdis/jiw525.

  PMID: 27811319 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Maraviroc; Emtricitabine; 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)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Organophosphonates; Organophosphorus Compounds; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Chunyuan Wu
• Organization: Fred Hutchinson cancer Research center

cwu@scharp.org

206-667-5567

Study Officials

• Roy M. Gulick, MD, MPH

  Weill Medical College of Cornell University

  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: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2012
• First Posted: January 6, 2012
• Study Start: June 1, 2012
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2015
• Last Updated: November 5, 2021
• Results First Posted: July 18, 2017

Record last verified: 2017-06

Locations

US (12); PR (1)