HIV Infection
Conditions
Keywords
HIV Prevention, PrEP, Maraviroc
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.
Detailed description
Several clinical trials are currently under way evaluating the safety and efficacy of ARV-based PrEP for preventing HIV infection. In 2010, the results of the first efficacy trial of ARV-based PrEP showed 44% fewer HIV infections among study participants receiving the study drugs (TDF and FTC) than among those receiving placebo. Although these results are promising, concerns about poor adherence, drug resistance, and toxicity prompt further exploration of ARV PrEP regimens. This trial will evaluate the safety and tolerability of PrEP using four ARV regimens in reducing HIV transmission in at-risk men who have sex with men and in at-risk women. 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.
Interventions
DRUGMaraviroc
300-mg tablet, once daily, from Week 0 through Week 48
DRUGEmtricitabine
200-mg capsule, once daily, from Week 0 through Week 48
DRUGTenofovir disoproxil fumarate
300-mg tablet, once daily, from Week 0 through Week 48
OTHERMaraviroc placebo
Once daily from Week 0 through Week 48
OTHEREmtricitabine placebo
Once daily from Week 0 through Week 48
Once daily from Week 0 through Week 48
Sponsors
HIV Prevention Trials Network
Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* For participants in the men's component of the study, born male. For participants in the women's component of the study, born female. * 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. Inclusion Criteria for the Tissue Subset: * 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
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of Grade 3 or Higher Adverse Events (AEs) | Through Week 48 | participants had Occurrence of Grade 3 or higher adverse events (AEs) |
Countries
Puerto Rico, United States
Participant flow
Recruitment details
The study started the enrollment in June 2012. Accrual will occur in a staggered fashion, with men beginning first and women beginning several months later. Accrual for the men will occur over approximately 9 months, and accrual for the women will require approximately 9 months.
Pre-assignment details
Exclusion--reactive HIV test results;Co-enrollment in any other HIV interventional research study; Use of ARV therapy; Prior history of any procedure altering the gastrointestinal tract or drug absorption; Receipt of prohibited medications; Known allergy to soy/peanuts; Weight\>300 lbs;
Participants by arm
| Arm | Count |
|---|---|
| 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 | 147 |
| 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 | 151 |
| 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 | 148 |
| 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 | 148 |
| Total | 594 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Death | 1 | 0 | 0 | 1 |
| Overall Study | inadvertent enrollment due to peanut all | 0 | 0 | 0 | 1 |
| Overall Study | investigator decision | 1 | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 11 | 5 | 8 | 7 |
| Overall Study | relocated | 4 | 2 | 2 | 3 |
| Overall Study | staff safety concerns | 0 | 0 | 0 | 1 |
| Overall Study | unable to adhere to visit schedule | 3 | 2 | 3 | 3 |
| Overall Study | Withdrawal by Subject | 5 | 4 | 4 | 7 |
Baseline characteristics
| Characteristic | Total | Arm 1 | Arm 2 | Arm 3 | Arm 4 |
|---|---|---|---|---|---|
| Age, Continuous Women | 36 years | 40 years | 36 years | 37 years | 37 years |
| Age, Continuous | 30 years | 30 years | 29.5 years | 30 years | 31 years |
| education 8th Grade or Less | 5 Participants | 1 Participants | 3 Participants | 0 Participants | 1 Participants |
| education Finished College | 153 Participants | 37 Participants | 40 Participants | 36 Participants | 40 Participants |
| education High School Graduate or Equivalent | 114 Participants | 35 Participants | 27 Participants | 25 Participants | 27 Participants |
| education masters or other advanced degree | 61 Participants | 10 Participants | 24 Participants | 17 Participants | 10 Participants |
| education Some College or 2 Year Degree | 206 Participants | 51 Participants | 43 Participants | 57 Participants | 55 Participants |
| education Some High School | 32 Participants | 10 Participants | 7 Participants | 6 Participants | 9 Participants |
| education Vocational/Trade/Technical School | 23 Participants | 3 Participants | 7 Participants | 7 Participants | 6 Participants |
| Employment Status Full-time Employment | 257 Participants | 56 Participants | 68 Participants | 59 Participants | 74 Participants |
| Employment Status Not Employed | 202 Participants | 53 Participants | 48 Participants | 52 Participants | 49 Participants |
| Employment Status Part-time Employment | 134 Participants | 38 Participants | 35 Participants | 36 Participants | 25 Participants |
| Marital Status Living with Primary Partner | 92 Participants | 25 Participants | 21 Participants | 25 Participants | 21 Participants |
| Marital Status Married/Civil Union/Legal Partnership | 38 Participants | 8 Participants | 9 Participants | 7 Participants | 14 Participants |
| Marital Status Not Living with Primary Partner | 62 Participants | 12 Participants | 17 Participants | 19 Participants | 14 Participants |
| Marital Status Other | 3 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants |
| Marital Status Single/Divorced/Widowed | 399 Participants | 102 Participants | 103 Participants | 96 Participants | 98 Participants |
| Race/Ethnicity, Customized American Indian/Alaskan Native | 17 Participants | 4 Participants | 6 Participants | 2 Participants | 5 Participants |
| Race/Ethnicity, Customized Asian | 17 Participants | 6 Participants | 1 Participants | 5 Participants | 5 Participants |
| Race/Ethnicity, Customized Black or African | 238 Participants | 61 Participants | 64 Participants | 62 Participants | 51 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Pacific Islander | 7 Participants | 1 Participants | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Other | 55 Participants | 15 Participants | 14 Participants | 10 Participants | 16 Participants |
| Race/Ethnicity, Customized White | 303 Participants | 73 Participants | 80 Participants | 72 Participants | 78 Participants |
| Sex: Female, Male Female | 188 Participants | 46 Participants | 45 Participants | 49 Participants | 48 Participants |
| Sex: Female, Male Male | 406 Participants | 101 Participants | 106 Participants | 99 Participants | 100 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 147 | 1 / 151 | 1 / 148 | 0 / 148 |
| other Total, other adverse events | 78 / 147 | 86 / 151 | 84 / 148 | 91 / 148 |
| serious Total, serious adverse events | 10 / 147 | 5 / 151 | 4 / 148 | 11 / 148 |
Outcome results
Primary
Occurrence of Grade 3 or Higher Adverse Events (AEs)
participants had Occurrence of Grade 3 or higher adverse events (AEs)
Time frame: Through Week 48
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1 | Occurrence of Grade 3 or Higher Adverse Events (AEs) | 18 Participants |
| Arm 2 | Occurrence of Grade 3 or Higher Adverse Events (AEs) | 24 Participants |
| Arm 3 | Occurrence of Grade 3 or Higher Adverse Events (AEs) | 20 Participants |
| Arm 4 | Occurrence of Grade 3 or Higher Adverse Events (AEs) | 28 Participants |