The ADAPT Study: Use of Emtricitabine and Tenofovir Disop... | NCT01327651

NCT01327651

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
10852	Registry Identifier	DAIDS-ES

Status Module

Description Module

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.

Label	Type	Description	Intervention Names
Daily dosing	Active Comparator	Participants will receive oral FTC/TDF daily.	Drug: Daily dosing
Time-driven dosing	Experimental	Participants will receive oral FTC/TDF twice weekly with a post-exposure dose.	Drug: Time-driven dosing
Event-driven dosing	Experimental	Participants will receive oral FTC/TDF before and after a potential exposure to HIV infection.	Drug: Event-driven dosing

Name	Type	Description	Arm Group Labels	Other Names
Daily dosing	Drug	A fixed-dose combination of emtricitabine and tenofovir disoproxil fumarate.	Daily dosing

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.	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)	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	From week 6 (randomization week) to week 30 (end of self-administered dosing)

Secondary Outcomes

Measure	Description	Time Frame
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

Eligibility Module

Eligibility Criteria

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

Name	Affiliation	Role
Robert M. Grant, MD, MPH	University of California, San Francisco	Study Chair
Frits van Griensven, PhD, MPH	School of Medicine, University of California at San Francisco	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Harlem Prevention Center CRS		New York	New York	10027	United States
Emavundleni CRS

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
21091279	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.
35080038

Arm/Group Information

ID	Title	Description
FG000	Daily Dosing, Cape Town	Cape Town participants will receive oral FTC/TDF daily. Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF): A fixed-dose combination of emtricitabine and tenofovir disoproxil fumarate, two nucleoside reverse transcriptase inhibitors.
FG001	Time-driven Dosing, Cape Town	Cape Town participants will receive oral FTC/TDF twice weekly with a post-exposure dose. Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF): A fixed-dose combination of emtricitabine and tenofovir disoproxil fumarate, two nucleoside reverse transcriptase inhibitors.
FG002	Event-driven Dosing, Cape Town	Cape Town participants will receive oral FTC/TDF before and after a potential exposure to HIV infection. Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF): A fixed-dose combination of emtricitabine and tenofovir disoproxil fumarate, two nucleoside reverse transcriptase inhibitors.
FG003	Daily Dosing, Bangkok	Bangkok participants will receive oral FTC/TDF daily. Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF): A fixed-dose combination of emtricitabine and tenofovir disoproxil fumarate, two nucleoside reverse transcriptase inhibitors.
FG004	Time-driven Dosing, Bangkok	Bangkok participants will receive oral FTC/TDF twice weekly with a post-exposure dose. Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF): A fixed-dose combination of emtricitabine and tenofovir disoproxil fumarate, two nucleoside reverse transcriptase inhibitors
FG005	Event-driven Dosing, Bangkok	Bangkok participants will receive oral FTC/TDF before and after a potential exposure to HIV infection. Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF): A fixed-dose combination of emtricitabine and tenofovir disoproxil fumarate, two nucleoside reverse transcriptase inhibitors.
FG006	Daily Dosing, Harlem	Harlem participants will receive oral FTC/TDF daily. Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF): A fixed-dose combination of emtricitabine and tenofovir disoproxil fumarate, two nucleoside reverse transcriptase inhibitors.
FG007	Time-driven Dosing, Harlem	Harlem participants will receive oral FTC/TDF twice weekly with a post-exposure dose. Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF): A fixed-dose combination of emtricitabine and tenofovir disoproxil fumarate, two nucleoside reverse transcriptase inhibitors.
FG008	Event-driven Dosing, Harlem	Harlem participants will receive oral FTC/TDF before and after a potential exposure to HIV infection. Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF): A fixed-dose combination of emtricitabine and tenofovir disoproxil fumarate, two nucleoside reverse transcriptase inhibitors.

Periods

Title

Milestones

Reasons Not Completed

Self-administered Dosing Period

Type	Comment	Milestone Data
STARTED	Week 6 (Randomization visit)	FG00060 subjects FG00159 subjects FG00260 subjects FG00360 subjects FG004
Week 10		FG00059 subjects FG00158 subjects FG00260 subjects FG00360 subjects FG004
Week 14		FG00059 subjects FG00155 subjects FG00257 subjects FG00360 subjects FG004
Week 18		FG00057 subjects FG00156 subjects FG00256 subjects FG00360 subjects FG004
Week 22		FG00059 subjects FG00156 subjects FG00255 subjects FG00358 subjects FG004
Week 26		FG00058 subjects FG00156 subjects FG00253 subjects FG00357 subjects FG004
COMPLETED	Week 30	FG00056 subjects FG00156 subjects FG00256 subjects FG00357 subjects
NOT COMPLETED		FG0004 subjects FG0013 subjects FG0024 subjects FG0033 subjects FG004

Type	Comment	Reasons
Lost to Follow-up		FG0003 subjects FG0012 subjects FG0024 subjects FG003

Post Study Follow-up

Type	Comment	Milestone Data
STARTED	Week 30	FG00056 subjects FG00156 subjects FG00256 subjects FG003

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Daily Dosing, Cape Town	Cape Town participants will receive oral FTC/TDF daily. Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF): A fixed-dose combination of emtricitabine and tenofovir disoproxil fumarate, two nucleoside reverse transcriptase inhibitors.
BG001	Time-driven Dosing, Cape Town

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Median

Outcome Measures Module

Outcome Measures

Type	Title	Description	Population Description	Reporting Status	Anticipated Posting Date	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Time Frame	Units Analyzed	Denominator Units Selected	Arm/Group Information	Denominators	Classes	Analyses
Primary	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.	For Cape Town daily dosing arm, there are originally 60 participants, but 1 participant was later found to be HIV infected on or before randomization visit, which should make this participant not eligible for the study analysis, so we removed this participant from this table. Given this, we left 59 participants in Cape Town daily dosing arm	Posted		Number		percentage of sexual exposures		From week 6 (randomization week) to week 30 (end of self-administered dosing)

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Daily Dosing, Cape Town	Cape Town participants will receive oral FTC/TDF daily. Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF): A fixed-dose combination of emtricitabine and tenofovir disoproxil fumarate, two nucleoside reverse transcriptase inhibitors.

ID	Term
D000086982	Blood-Borne Infections
D003141	Communicable Diseases
D007239	Infections
D015229	Sexually Transmitted Diseases, Viral

ID	Term
D063065	Organophosphonates
D009943	Organophosphorus Compounds
D009930	Organic Chemicals
D000225	Adenine