HIV Infections
Conditions
Brief summary
This study will assess the uptake, acceptability, safety, and feasibility of HIV pre-exposure prophylaxis (PrEP), consisting of a once-daily fixed-dose combination tablet of emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF), administered at sexually transmitted disease (STD) clinics and a community health center in the United States.
Detailed description
A previous study (iPrEx) showed that daily PrEP with FTC/TDF provided with a comprehensive package of prevention services is effective in preventing HIV infection among men who have sex with men (MSM). The PrEP administered in that study was given in the context of a research setting/controlled trial, but it is important to evaluate the acceptability, sustainability, and safety of PrEP in a real world setting. This study will evaluate PrEP administered to HIV-uninfected MSM and transgender females at two STD clinics and one community health center in the United States. Each participant will receive PrEP for up to 1 year and will have up to 8 study visits. PrEP will consist of one fixed-dose FTC/TDF combination tablet orally each day. All participants will have study visits at screening, enrollment, and 4 weeks after enrollment; participants will continue to have visits at Weeks 12, 24, 36, 48, and 52 if they do not seroconvert. Participants who seroconvert will discontinue PrEP and will have a post-drug discontinuation visit 4 weeks after discontinuing PrEP. At most visits, participants will undergo blood, urine, and hair sample collection; give a medical history; undergo a physical exam; receive risk-reduction counseling and condoms; undergo testing for HIV and other STDs; receive study drugs; and undergo a pill count and adherence assessment (follow-up visits only). For participants who stop taking the study drug but remain in the study, urine, blood, and hair samples will not be collected at 12-week follow-up visits if all stop procedures have been completed and if there are no lab abnormalities that require additional follow-up. Participants will also answer questionnaires at screening, 12-week visits, and at study exit.
Interventions
DRUGFTC 200 mg/TDF 300 mg fixed-dose combination tablet
Each participant will be directed to take one FTC/TDF tablet orally once a day, with or without food.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Must be either a man who has sex with men or a transgender female * Male sex (at birth) * Willing and able to provide written informed consent * HIV-1 uninfected, defined as having a negative rapid HIV antibody test at both screening visit and enrollment and a negative 4th generation antibody/antigen test at screening * No laboratory evidence of a detectable HIV viral load (San Francisco site only) * Evidence of risk of acquiring HIV-1 infection including any one of the following: (1) Condomless anal sex with two or more male or transgender female sex partners during the last 12 months; or (2) two or more episodes of anal sex with at least one HIV-positive partner during the last 12 months; or (3) sex with a male or transgender female partner and any of the following STDs diagnosed during the last 12 months or at screening: syphilis, rectal gonorrhea, or rectal chlamydia. * Able to provide a street address of residence or phone number for themselves or two personal contacts who would know their whereabouts during the period of the demonstration project * Adequate renal function: creatinine clearance of 60 ml/min or greater as estimated by the Cockcroft-Gault equation within 45 days of enrollment * A urine dipstick with a negative or trace result for protein within 45 days of enrollment * Fluent in English or in Spanish
Exclusion criteria
* Signs or symptoms of acute HIV infection * Previously diagnosed active and serious infections including active tuberculosis infection or osteomyelitis and all infections requiring parenteral antibiotic therapy (other than STDs requiring intramuscular injections of antibiotics); active clinically significant medical problems including poorly controlled cardiac disease (e.g., symptoms of ischemia or congestive heart failure) or previously diagnosed malignancy expected to require further treatment * Hepatitis B surface antigen (HBsAg) positive * History of pathological bone fractures not related to trauma * Receiving ongoing therapy with any of the following: investigational antiretroviral agents (PEP is allowed as described in the protocol), interferon (alpha, beta, or gamma) or interleukin (e.g., IL-2) therapy, agents with significant nephrotoxic potential, other agents that may inhibit or compete for elimination via active renal tubular secretion (e.g., probenecid), and/or other investigational agents * Concomitant participation in a clinical trial using investigational agents, including placebo-controlled clinical trials using such agents * At enrollment, has any other condition that, based on the opinion of the investigator or designee, would preclude provision of informed consent; make participation in the project unsafe; complicate interpretation of outcome data; or otherwise interfere with achieving the project objectives
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Measurement of PrEP Adherence by Medication Possession Ratio | Participants were followed for 48 weeks, or up to the point of early termination | Medication possession ratio is defined as the number of dispensed pills divided by the number of days between visits |
| Measurement of PrEP Adherence by TFV-DP Levels in DBS | Participants were followed for 48 weeks, or up to the point of early termination | — |
| Number of Male Sexual Partners | Participants were followed for 48 weeks, or up to the point of early termination | — |
| Measurement of Acceptance Rate of PrEP | Measured through enrollment (Week 0) | — |
| Measurement of Refusal Rate of PrEP | Measured through enrollment (Week 0) | — |
| Duration of PrEP Use | Participants were followed for 48 weeks, or up to the point of early termination | Number of study drug interruptions |
| Measurement of Side Effects/Toxicities | Participants were followed for 48 weeks, or up to the point of early termination | — |
Secondary
| Measure | Time frame |
|---|---|
| Measurement of HIV Drug Resistance Patterns Among Participants Who Become Infected | Participants were followed for 48 weeks, or up to the point of early termination |
| Number of Participants Who Seroconvert | Participants were followed for 48 weeks, or up to the point of early termination |
Countries
United States
Participant flow
Recruitment details
Participants were screened and enrolled at 3 sites in the US (San Francisco, Miami, Washington DC). Enrollment began on October 1, 2012 and ended February 10, 2015.
Pre-assignment details
As this PrEP Demonstration project assessed acceptance of PrEP, all participants assessed for participation are included in the start category, and those who enrolled and initiated PrEP are indicated as a separate milestone.
Participants by arm
| Arm | Count |
|---|---|
| Emtricitabine (FTC)/Tenofovir Disoproxil Fumarate (TDF) All study participants will be assigned to this arm and will receive one FTC/TDF tablet orally once a day.
FTC 200 mg/TDF 300 mg fixed-dose combination tablet: Each participant will be directed to take one FTC/TDF tablet orally once a day, with or without food. | 557 |
| Total | 557 |
Baseline characteristics
| Characteristic | Emtricitabine (FTC)/Tenofovir Disoproxil Fumarate (TDF) |
|---|---|
| Age, Continuous | 33 years |
| Race/Ethnicity, Customized Asian | 26 Participants |
| Race/Ethnicity, Customized Black | 40 Participants |
| Race/Ethnicity, Customized Latino | 192 Participants |
| Race/Ethnicity, Customized Other | 32 Participants |
| Race/Ethnicity, Customized White | 266 Participants |
| Region of Enrollment United States | 557 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 557 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 25 / 557 |
| serious Total, serious adverse events | 19 / 557 |
Outcome results
Primary
Duration of PrEP Use
Number of study drug interruptions
Time frame: Participants were followed for 48 weeks, or up to the point of early termination
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants Assessed for Participation | Duration of PrEP Use | 86 interruptions |
Primary
Duration of PrEP Use
Mean duration of interruptions
Time frame: Participants were followed for 48 weeks, or up to the point of early termination
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants Assessed for Participation | Duration of PrEP Use | 65 Days |
Primary
Measurement of Acceptance Rate of PrEP
Time frame: Measured through enrollment (Week 0)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Participants Assessed for Participation | Measurement of Acceptance Rate of PrEP | Potentially eligible clients | 921 Participants |
| Participants Assessed for Participation | Measurement of Acceptance Rate of PrEP | Participants enrolled | 557 Participants |
Primary
Measurement of PrEP Adherence by Medication Possession Ratio
Medication possession ratio is defined as the number of dispensed pills divided by the number of days between visits
Time frame: Participants were followed for 48 weeks, or up to the point of early termination
Population: Mean PrEP adherence by medication possession ratio
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants Assessed for Participation | Measurement of PrEP Adherence by Medication Possession Ratio | 85.9 percent |
Primary
Measurement of PrEP Adherence by TFV-DP Levels in DBS
Time frame: Participants were followed for 48 weeks, or up to the point of early termination
Population: DBS testing was performed in approximately 100 randomly selected participants per site, and among all African American and transgender participants, who were underrepresented in the overall sample
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Participants Assessed for Participation | Measurement of PrEP Adherence by TFV-DP Levels in DBS | % with protective TFV-DP levels at week 4 | 86 Percent of Participants |
| Participants Assessed for Participation | Measurement of PrEP Adherence by TFV-DP Levels in DBS | % with protective TFV-DP levels at week 12 | 85 Percent of Participants |
| Participants Assessed for Participation | Measurement of PrEP Adherence by TFV-DP Levels in DBS | % with protective TFV-DP levels at week 24 | 82 Percent of Participants |
| Participants Assessed for Participation | Measurement of PrEP Adherence by TFV-DP Levels in DBS | % with protective TFV-DP levels at week 36 | 85 Percent of Participants |
| Participants Assessed for Participation | Measurement of PrEP Adherence by TFV-DP Levels in DBS | % with protective TFV-DP levels at week 48 | 80 Percent of Participants |
Primary
Measurement of Refusal Rate of PrEP
Time frame: Measured through enrollment (Week 0)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Participants Assessed for Participation | Measurement of Refusal Rate of PrEP | Potentially eligible clients | 921 Participants |
| Participants Assessed for Participation | Measurement of Refusal Rate of PrEP | Declined participation | 364 Participants |
Primary
Measurement of Side Effects/Toxicities
Time frame: Participants were followed for 48 weeks, or up to the point of early termination
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Participants Assessed for Participation | Measurement of Side Effects/Toxicities | Serious adverse events | 19 events |
| Participants Assessed for Participation | Measurement of Side Effects/Toxicities | Creatinine elevations | 23 events |
Primary
Number of Male Sexual Partners
Time frame: Participants were followed for 48 weeks, or up to the point of early termination
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Participants Assessed for Participation | Number of Male Sexual Partners | Mean Anal sex partners at baseline | 10.9 partners |
| Participants Assessed for Participation | Number of Male Sexual Partners | Mean Anal sex partners at week 48 | 9.3 partners |
Secondary
Measurement of HIV Drug Resistance Patterns Among Participants Who Become Infected
Time frame: Participants were followed for 48 weeks, or up to the point of early termination
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants Assessed for Participation | Measurement of HIV Drug Resistance Patterns Among Participants Who Become Infected | 1 participant with acquired HIV resistance |
Secondary
Number of Participants Who Seroconvert
Time frame: Participants were followed for 48 weeks, or up to the point of early termination
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Participants Assessed for Participation | Number of Participants Who Seroconvert | Acute HIV infection at baseline | 3 participants |
| Participants Assessed for Participation | Number of Participants Who Seroconvert | HIV seroconversion during follow-up | 2 participants |