The ADAPT Study: Use of Emtricitabine and Tenofovir Disoproxil Fumarate for Pre-Exposure Prophylaxis (PrEP)

Phase 2

Completed

Conditions: HIV Infections

Interventions: Drug: Daily dosing
Drug: Time-driven dosing
Drug: Event-driven dosing

Registration Number: NCT01327651

Lead Sponsor: HIV Prevention Trials Network

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 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 622

Inclusion Criteria

Literacy in one of the study languages (Thai, Xhosa, and/or English)
Able to provide written informed consent
Able to provide weekly telephonic updates
Within 70 days of enrollment:
1. Serum creatinine less than or equal to the upper limit of normal (ULN) and calculated creatinine clearance of at least 70 mL/min by the Cockcroft-Gault formula. More information on this criterion can be found in the protocol.
2. Serum phosphate greater than or equal to the lower limit of normal (LLN)
3. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 2 times ULN
4. Hemoglobin greater than 10 g/dL
5. Hepatitis B surface antigen (HBsAg)-negative
6. Willing and able to provide adequate locator information

Inclusion Criteria for MSM/TGW:

Male at birth
Reporting anal intercourse and/or receptive neovaginal intercourse with at least one man or transgender woman in the past 6 months
One or more of the following risk factors for HIV acquisition in the past 6 months according to self-report: sexual intercourse with more than one man or transgender woman; history of an acute sexually transmitted infection (STI); sex in exchange for money, goods, or favors; condomless intercourse (oral, anal, vaginal, or neovaginal) with a partner known to be HIV-infected or of unknown HIV infection status according to self report

Inclusion Criteria for Women Who Have Sex With Men (WSM):

Female at birth or self identify as female
Not pregnant or breastfeeding
Not able to or not intending to become pregnant during the next year
If able to become pregnant, self reported use of an effective method of contraception at Enrollment, and intending to use an effective method for the next 34 weeks
One or more of the following risk factors for HIV acquisition in the past 6 months according to self report: sexual intercourse with more than one man; history of an acute STI; sex in exchange for money, goods or favors; condomless intercourse (oral, anal, or vaginal) with a partner known to be HIV-infected or of unknown HIV infection status

Exclusion Criteria

Proteinuria 2+ or greater at screening
Glucosuria 2+ or greater at screening
Serious and active medical or mental illness
One or both HIV rapid tests is reactive at screening or enrollment, regardless of subsequent HIV diagnostic test results
Signs or symptoms suggestive of acute HIV infection
Use of hypoglycemic agents for diabetes or agents with known nephrotoxic potential
Use of ARV therapy (e.g., for post-exposure prophylaxis [PEP] or PrEP) in the 90 days prior to study entry
Serum phosphate level below site laboratory LLN
Current participation (or participation within 3 months of screening) in any HIV prevention study
Previous or current participation in the active arm of an HIV vaccine trial
Acute or chronic hepatitis B (HBV) infection (refers to chronic active HBV infection evidenced by a positive test for hepatitis B surface antigen (HBsAg)
Presence of a psychological or social condition or an addictive disorder that would preclude compliance with the protocol
Any other reason or condition that in the opinion of the investigator would interfere with participation, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Daily dosing	Daily dosing	Participants will receive oral FTC/TDF daily.
Time-driven dosing	Time-driven dosing	Participants will receive oral FTC/TDF twice weekly with a post-exposure dose.
Event-driven dosing	Event-driven dosing	Participants will receive oral FTC/TDF before and after a potential exposure to HIV infection.

Primary Outcome Measures

Name	Time	Method
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)	From week 6 (randomization week) to week 30 (end of self-administered dosing)	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)
The Total Pills Actually Used Over the Follow-up Period	From week 6 (randomization week) to week 30 (end of self-administered dosing)	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
Proportion of Sexual Exposures Covered by Pre- and Post-exposure Dosing	From week 6 (randomization week) to week 30 (end of self-administered 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.
Self-reported Side Effect or Symptom Scores	From week 6 (randomization week) to week 30 (end of self-administered dosing)	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

Secondary Outcome Measures

Name	Time	Method
The Proportion of Participants Who Discontinue All PrEP Use Based on Self-report Via CASI or Weekly Interviews	From Week 6 to Week 30
Measurement of TFV-DP (Tenofovir Diphosphate) in PBMC (Peripheral Blood Mononuclear Cell)	week 10, 18 and 30, which is 4 weeks, 12 weeks, and 24 weeks after randomization	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
A Listing of Adverse Events (AEs) by Grade, Relationship to Study Product, and Arm	From week 6 (randomization week) to week 30 (end of self-administered dosing)	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.
A Listing, by Arm, of Drug Resistance Test Results and Plasma HIV RNA Levels Among All Participants Who Seroconvert While on Study	From Enrollment to week 30 (end of self-administered dosing)	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
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	From week 6 (randomization week) to week 30 (end of self-administered dosing)

Trial Locations

Locations (3): Silom Community Clinic CRS
🇹🇭
Nonthaburi, Thailand
Emavundleni CRS
🇿🇦
Cape Town, Western Cape Province, South Africa
Harlem Prevention Center CRS
🇺🇸
New York, New York, United States