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.
No single strategy for the prevention of HIV has emerged as consistently used and successful, so multiple strategies have been developed. PrEP involves delivering ARV medications to people before they are exposed to HIV, in order to prevent infection. The optimal method of delivering PrEP has not yet been determined. This study will examine the feasibility of delivering PrEP in three methods. Daily dosing involves receiving ARV medications every day; time-driven dosing involves receiving ARV medications twice weekly plus a post-exposure dose; and event-driven dosing involves receiving ARV medications before and after a potential exposure to HIV. The ARV medication that will be used in this study is a combination pill that contains emtricitabine and tenofovir disoproxil fumarate (FTC/TDF). Recent research studies have shown that, if taken consistently, a daily oral dose of FTC/TDF can reduce the risk of HIV infection. This study will enroll HIV-uninfected men who have sex with men and transgender women (MSM/TGW) and women who have sex with men (WSM). Participation will last 34 weeks. All participants will be given a combination pill that contains FTC/TDF. For the first 5 weeks, all participants will come to the study clinic weekly to receive a single dose of FTC/TDF. At Week 6, participants will be randomly assigned to one of three groups. In the daily dosing group, participants will take FTC/TDF once a day. In the time-dosing group, participants will take FTC/TDF twice per week and another dose after sexual intercourse (a post-exposure dose). In the event-dosing group, participants will take FTC/TDF before and after sexual intercourse. During this part of the study, participants will be given FTC/TDF to take on their own. Every week, from Week 6 to Week 29, study officials will call to ask questions about how many pills participants have taken and when they have had sexual intercourse. Participants will also complete computer-assisted self-interviews (CASIs). Study visits will occur at enrollment, once a week for the first 5 weeks, and then once a month until Week 34. Assessment will include recording of medical history, completing an interview about sexual practices and background, and collection of blood, urine, and hair samples. Select study visits will include vaginal practices assessment (including use of lubricants and vaginal cleansing practices), family planning assessments (for women), and sex hormones assessments (for men). Participants who acquire HIV infection during the study will discontinue study product. These participants will continue to be followed after enrollment at Weeks 4, 6, 10, 14, 18, 22, 26, 30, and every 12 weeks thereafter, as appropriate, until the last study participant completes follow-up at the study site. Participants whose first reactive HIV rapid test is at Week 34 who are later confirmed to be HIV infected will also be followed every 12 weeks after their Week 30 visit until the last study participant completes follow-up at the study site. Participants who acquire HIV infection during the study will undergo select protocol procedures and will receive counseling and referrals for HIV treatment.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
622
A fixed-dose combination of emtricitabine and tenofovir disoproxil fumarate.
TDF/FTC twice weekly with a post-exposure dose
TDF/FTC as needed with a post exposure dose
Harlem Prevention Center CRS
New York, New York, United States
Emavundleni CRS
Cape Town, Western Cape, South Africa
Silom Community Clinic CRS
Nonthaburi, Thailand
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.
Time frame: 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)
Time frame: 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
Time frame: From week 6 (randomization week) to week 30 (end of self-administered dosing)
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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
Time frame: From week 6 (randomization week) to week 30 (end of self-administered dosing)
Measurement of TFV-DP (Tenofovir Diphosphate) in PBMC (Peripheral Blood Mononuclear Cell)
Below we presented the percentages of total cohort with TFV-DP concentrations consistent with \>=2 pills/week in women who also report sex in the last 7 day for each arm. For Cape Town and Bangkok, TFV-DP in PBMC was analyzed, for Harlem site, the TFV-DP in DBS (dried blood spot) was analyzed. Note: PBMC \>5.2 fmol/10\^6 cells is considered as participants taken \>=2 tablets per week; DBS \>=326 fmol/punch is considered as participants taken \>=2 tablets per week
Time frame: 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
Only the listing of adverse events (AEs) by grade and arm are presented here. See outcome measure 10 for the listing of AE by relationship to study product
Time frame: 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
Only the cross table between drug resistance by arm are presented here. See outcome measure 11 for the listing of plasma HIV RNA levels, and outcome measure 12 for the listing of drug resistance test by arm among all participants who seroconvert while on study.
Time frame: 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
Time frame: 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
Time frame: From Week 6 to Week 30
A Listing of Adverse Events (AEs) by Grade, Relationship to Study Product, and Arm
Only the listing of AE related to study product are presented here. See outcome measure 6 for the listing of adverse events (AEs) by grade and arm.
Time frame: 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
Only the listing of plasma HIV RNA levels among all participants who seroconvert while on study are presented here. See outcome measure 12 for the listing of drug resistance test by arm.
Time frame: From Enrollment 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
Only the listing of drug resistance test by arm among all participants who seroconvert while on study are presented here. See outcome measure 11 for the listing of plasma HIV RNA levels
Time frame: From Enrollment to week 30 (end of self-administered dosing)