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
NCT ID: NCT01505114
Last Updated: 2021-11-05
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE2
594 participants
INTERVENTIONAL
2012-06-30
2015-11-30
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Participants will be randomly assigned to one of four arms: Arm 1, Arm 2, Arm 3, or Arm 4. Arm 1 will receive MVC, FTC placebo, and TDF placebo orally once daily from Week 0 through 48. Arm 2 will receive MVC, FTC, and TDF placebo orally once daily from Week 0 through 48. Arm 3 will receive MVC, FTC placebo, and TDF orally once daily from Week 0 through 48. Participants in Arm 4 will receive MVC placebo, FTC, and TDF orally once daily from Week 0 through 48.
Study visits will occur at enrollment and Weeks 2, 4, 8, 16, 24, 32, 40, 48, and 49. All study visits will include a physical examination, blood collection and storage, and HIV counseling and testing. Select study visits will include adherence counseling, surveys, behavioral assessments (including sexual behavioral assessments), urine collection, and dual-energy x-ray absorptiometry (DXA). Participants will also undergo sexual behavioral assessments randomly 12 to 13 times through Week 48 via short message service (SMS). Some female participants may opt into taking part in an interview at Week 48.
Participants who enroll in this study may also consent to be a part of two subset evaluations as part of this study: the Drug Interaction Subset or the Tissue Subset. Enrollment in these subsets will involve additional study procedures. The Drug Interaction Subset will undergo blood collection before and after a directly observed dose of study drug at the Week 2 visit. Participants in the Tissue Subset will take part in additional study procedures at select visits, including blood collection, hair collection, and rectal tissue and fluid collection (required for men; optional for women). Women involved in the Tissue Subset will also undergo cervical tissue and cervicovaginal fluid collection at select visits.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Keywords
Explore important study keywords that can help with search, categorization, and topic discovery.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
PREVENTION
TRIPLE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Arm 1
MVC 300 mg plus FTC placebo and TDF placebo orally once daily
Maraviroc
300-mg tablet, once daily, from Week 0 through Week 48
Emtricitabine placebo
Once daily from Week 0 through Week 48
Tenofovir disoproxil fumarate placebo
Once daily from Week 0 through Week 48
Arm 2
MVC 300 mg plus FTC 200 mg and TDF placebo orally once daily
Maraviroc
300-mg tablet, once daily, from Week 0 through Week 48
Emtricitabine
200-mg capsule, once daily, from Week 0 through Week 48
Tenofovir disoproxil fumarate placebo
Once daily from Week 0 through Week 48
Arm 3
MVC 300 mg plus FTC placebo and TDF 300 mg orally once daily
Maraviroc
300-mg tablet, once daily, from Week 0 through Week 48
Tenofovir disoproxil fumarate
300-mg tablet, once daily, from Week 0 through Week 48
Emtricitabine placebo
Once daily from Week 0 through Week 48
Arm 4
MVC placebo plus FTC 200 mg and TDF 300 mg orally once daily
Emtricitabine
200-mg capsule, once daily, from Week 0 through Week 48
Tenofovir disoproxil fumarate
300-mg tablet, once daily, from Week 0 through Week 48
Maraviroc placebo
Once daily from Week 0 through Week 48
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Maraviroc
300-mg tablet, once daily, from Week 0 through Week 48
Emtricitabine
200-mg capsule, once daily, from Week 0 through Week 48
Tenofovir disoproxil fumarate
300-mg tablet, once daily, from Week 0 through Week 48
Maraviroc placebo
Once daily from Week 0 through Week 48
Emtricitabine placebo
Once daily from Week 0 through Week 48
Tenofovir disoproxil fumarate placebo
Once daily from Week 0 through Week 48
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* 18 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)
* For women, satisfactory Pap results in the 12 calendar months prior to enrollment consistent with Grade 0 according to the Female Genital Grading Table for Use in Microbicide Studies Addendum 1 to the DAIDS Table for Grading Adult and Pediatric Adverse Events, Version 1.0, December 2004 (Clarification dated August 2009), or satisfactory evaluation with no treatment required of Grade 1 or higher Pap result per American Society for Colposcopy and Cervical Pathology (ASCCP) guidelines in the 12 calendar months prior to enrollment. If there is no document of satisfactory Pap results, the participant should be offered to have the test performed by the site prior to the enrollment visit. If they refuse, they are not eligible.
Exclusion Criteria
* 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)
* Active untreated syphilis, gonorrhea, or chlamydia infection
For Women Only:
* Carcinoma in situ of the cervix or invasive cervical cancer. Abnormalities of the vaginal mucosa or significant vaginal 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, and infectious or inflammatory condition of the local mucosa).
* Hysterectomy
* Per participant report at screening, anticipated use and/or unwillingness to abstain from vaginally administered medications (including over-the-counter products) and vaginal douching for 3 days prior to cervical biopsies and for 7 days after biopsies
18 Years
ALL
Yes
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
HIV Prevention Trials Network
NETWORK
Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
NETWORK
National Institute of Allergy and Infectious Diseases (NIAID)
NIH
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Roy M. Gulick, MD, MPH
Role: STUDY_CHAIR
Weill Medical College of Cornell University
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
UCLA CARE Center CRS
Los Angeles, California, United States
Bridge HIV CRS
San Francisco, California, United States
George Washington Univ. CRS
Washington D.C., District of Columbia, United States
Johns Hopkins University CRS
Baltimore, Maryland, United States
Fenway Health (FH) CRS
Boston, Massachusetts, United States
New Jersey Medical School Clinical Research Center CRS
Newark, New Jersey, United States
Weill Cornell Chelsea CRS
New York, New York, United States
Chapel Hill CRS
Chapel Hill, North Carolina, United States
Case Clinical Research Site
Cleveland, Ohio, United States
Penn Therapeutics, CRS
Philadelphia, Pennsylvania, United States
University of Pittsburgh CRS
Pittsburgh, Pennsylvania, United States
University of Washington AIDS CRS
Seattle, Washington, United States
Puerto Rico AIDS Clinical Trials Unit CRS
San Juan, , Puerto Rico
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
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.
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.
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.
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.
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.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
11789
Identifier Type: REGISTRY
Identifier Source: secondary_id
HPTN 069/A5305
Identifier Type: -
Identifier Source: secondary_id
HPTN 069
Identifier Type: -
Identifier Source: secondary_id
HPTN 069/NEXT Prep
Identifier Type: -
Identifier Source: secondary_id
HPTN 069/A5305 (NEXT Prep)
Identifier Type: -
Identifier Source: org_study_id