HIV Prevention
Conditions
Brief summary
The purpose of this study is to evaluate the safety, acceptability and feasibility of delivery of Pre-Exposure Prophylaxis (PrEP) or Post-Exposure Prophylaxis) PEP as part of combination HIV prevention services for high-risk MSM and transgender women.
Detailed description
Two community-based sites (LALGBT Center and The OASIS Clinic) will serve as facilities at which participants may present for screening for prevention services. At the sites, eligibility criteria will be assessed, HIV, Sexually Transmitted Disease (STD) and laboratory testing will be performed, and HIV prevention service referrals will be initiated. Follow-up will be on a monthly basis for the first three months, and then de-escalated to an every-3-month interval. The program stratifies participants into two cohorts on the basis of sexual risk behavior: a low-moderate risk cohort (LM) and a high-risk cohort (H). Participants in the LM cohort will be provided a customized prevention package (CPP) including access to PEP for emergency HIV prevention in the event of unanticipated HIV exposure. Participants in the H cohort will be provided a CPP including daily Truvada-based PrEP. All participants will be followed for 48 weeks. Participants in the LM cohort who, on longitudinal sexual risk behavior surveillance, report increased levels of sexual risk-taking such that they meet enrollment criteria for the H-cohort will be transitioned to the H-cohort. At each follow-up visit, a careful safety assessment will be made, including signs/symptoms and laboratory assessments. STD testing will be performed at 3 month intervals. An escalating-intensity adherence intervention will be implemented based on real-time plasma tenofovir levels. A computer-assisted self-interview (CASI) will be used to capture detailed sexual risk, adherence, and substance use behavior.
Interventions
DRUGemtricitabine 200mg/tenofovir 300mg
The intervention medication will be tenofovir + emtricitabine, provided as a fixed-dose combination tablet as Truvada®. Dosing is 1 tablet by mouth once daily. For participants with a a confirmed (i.e. two consecutive) reduction in creatinine clearance (CrCl) to \<50 mL/min, Truvada will be dose-reduced to 1 tablet by mouth every other day. For patients with CrCl \<30 mL/min, Truvada will be discontinued.
Sponsors
Los Angeles County Department of Public Health
Los Angeles LGBT Center
The OASIS Clinic
AIDS Project Los Angeles
University of California, Los Angeles
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* At least 18 years of age * Able to understand and provide consent in English or Spanish * Self identified MSM, MSM/W, or Transfemale * At least one male sex partner for anal intercourse in the prior 12 months * HIV negative by enzyme immunoassay (EIA) and viral load (VL) * CrCl ≥ 60 ml/min (via Cockcroft-Gault formula) * No signs or symptoms suggestive of primary HIV infection (PHI).
Exclusion criteria
* Participants \<18 years of age * Unable to understand and provide consent in English or Spanish * Known or found on testing to be HIV positive * Any condition, which in the opinion of the intake provider, will seriously compromise the participant's ability to comply with the protocol, including adherence to PEP or PrEP medication dosing * Use of Antiretroviral therapy (ART) taken for any indication (i.e. PEP or PrEP) within 60 days of study entry * Previous participation in an HIV vaccine trial. Participants that were documented to have received only placebo are not excluded. * Signs or symptoms suspicious for PHI.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Grade 2 or Higher Adverse Event by Cohort | Baseline to 48 weeks | Number and frequency rate of clinical and laboratory AEs (Gr 2 and above), including SAEs by Cohort. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cohort H PrEP Engagement by Study Visit | Baseline to 48 weeks | Optimal adherence to daily oral emtricitabine/tenofovir disoproxil fumarate by study visit as measured by tenofovir diphosphate (TFV-DP) in dried blood spots (DBS). Optimal adherence is defined as TFV-DP levels great than or equal to 700 femtomoles per punch in DBS samples (approximately 4 or more doses a week over the past 60 days). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Escalation in Transmission Risk Behavior Among Participants Reporting Low Risk Behaviors at Baseline | Baseline to 48 weeks | Changes in sexual risk behavior as assessed via CASI-based self-report questionnaire, measured longitudinally over time. |
| Number of HIV Seroconversions by Cohort. | Baseline to 48 weeks | — |
Countries
United States
Participant flow
Pre-assignment details
Of the 328 participants who enrolled in the study, 27 screen failed for various reasons and were not assigned to a cohort.
Participants by arm
| Arm | Count |
|---|---|
| Cohort H (PrEP) Participants in the H cohort will be provided with a CPP (customized prevention package) including daily Truvada-based PrEP(Pre-Exposure Prophylaxis).
High Risk Cohort Criteria (one or more of the following has to be met):
1. No condom use during anal intercourse with ≥3 male sex partners who are HIV-positive or of unknown HIV status during the last three months.
2. STI diagnosis during the last 12 months.
3. Previous PEP use during the last 12 months (\* see exclusion criteria)
4. Has at least one HIV infected sexual partner for ≥4 weeks.
emtricitabine 200mg/tenofovir 300mg: The intervention medication will be tenofovir + emtricitabine, provided as a fixed-dose combination tablet as Truvada®. Dosing is 1 tablet by mouth once daily. For participants with a a confirmed (i.e. two consecutive) reduction in CrCl to \<50 mL/min, Truvada will be dose-reduced to 1 tablet by mouth every other day. For patients with creatinine clearance \<30 mL/min, Truvada will be discontinued. | 297 |
| Cohort LM (PEP) Participants who do not meet criteria for High Risk (Cohort H) will be assigned to the LM (low moderate) cohort and will receive a customized prevention package based on baseline assessments (in the same manner as the Cohort H Participants). In addition, they will receive education on the availability and use of post-exposure prophylaxis.
emtricitabine 200mg/tenofovir 300mg: The intervention medication will be tenofovir + emtricitabine, provided as a fixed-dose combination tablet as Truvada®. Dosing is 1 tablet by mouth once daily. For participants with a a confirmed (i.e. two consecutive) reduction in CrCl to \<50 mL/min, Truvada will be dose-reduced to 1 tablet by mouth every other day. For patients with creatinine clearance \<30 mL/min, Truvada will be discontinued. | 4 |
| Total | 301 |
Baseline characteristics
| Characteristic | Cohort H (PrEP) | Cohort LM (PEP) | Total |
|---|---|---|---|
| Age, Continuous | 33 years | 35 years | 34 years |
| Education Any postgraduate | 55 Participants | 1 Participants | 56 Participants |
| Education College graduate | 104 Participants | 2 Participants | 106 Participants |
| Education High school or less | 33 Participants | 0 Participants | 33 Participants |
| Education Some college | 105 Participants | 1 Participants | 106 Participants |
| Family Income $20,000 or less | 92 Participants | 0 Participants | 92 Participants |
| Family Income $20,001 - $50,000 | 111 Participants | 3 Participants | 114 Participants |
| Family Income $50,001 or more | 94 Participants | 1 Participants | 95 Participants |
| Insurance Insured | 200 Participants | 1 Participants | 201 Participants |
| Insurance Uninsured | 91 Participants | 2 Participants | 93 Participants |
| Insurance Unknown | 6 Participants | 1 Participants | 7 Participants |
| Marital Status Have primary or main partner, not living together | 39 Participants | 0 Participants | 39 Participants |
| Marital Status Living with primary or main partner | 42 Participants | 0 Participants | 42 Participants |
| Marital Status Married/civil union/legal partnership | 9 Participants | 0 Participants | 9 Participants |
| Marital Status Other | 12 Participants | 0 Participants | 12 Participants |
| Marital Status Single/divorced/widowed | 194 Participants | 4 Participants | 198 Participants |
| Marital Status Unknown | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 14 Participants | 1 Participants | 15 Participants |
| Race/Ethnicity, Customized Hispanic/Latino | 82 Participants | 1 Participants | 83 Participants |
| Race/Ethnicity, Customized Mixed Race/Other | 16 Participants | 1 Participants | 17 Participants |
| Race/Ethnicity, Customized Non-Hispanic Black | 30 Participants | 0 Participants | 30 Participants |
| Race/Ethnicity, Customized Non-Hispanic White | 150 Participants | 1 Participants | 151 Participants |
| Race/Ethnicity, Customized Pacific Islander/Alaskan Native | 4 Participants | 0 Participants | 4 Participants |
| Region of Enrollment United States | 297 Participants | 4 Participants | 301 Participants |
| Sex/Gender, Customized Male Male | 296 Participants | 4 Participants | 300 Participants |
| Sex/Gender, Customized Male Transfemale | 1 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 195 / 297 | 0 / 4 |
| serious Total, serious adverse events | 2 / 297 | 0 / 4 |
Outcome results
Primary
Number of Participants With a Grade 2 or Higher Adverse Event by Cohort
Number and frequency rate of clinical and laboratory AEs (Gr 2 and above), including SAEs by Cohort.
Time frame: Baseline to 48 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort H (PrEP) | Number of Participants With a Grade 2 or Higher Adverse Event by Cohort | 230 Participants |
| Cohort LM (PEP) | Number of Participants With a Grade 2 or Higher Adverse Event by Cohort | 0 Participants |
Secondary
Cohort H PrEP Engagement by Study Visit
Optimal adherence to daily oral emtricitabine/tenofovir disoproxil fumarate by study visit as measured by tenofovir diphosphate (TFV-DP) in dried blood spots (DBS). Optimal adherence is defined as TFV-DP levels great than or equal to 700 femtomoles per punch in DBS samples (approximately 4 or more doses a week over the past 60 days).
Time frame: Baseline to 48 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort H (PrEP) | Cohort H PrEP Engagement by Study Visit | Week 4 | 246 Participants |
| Cohort H (PrEP) | Cohort H PrEP Engagement by Study Visit | Week 12 | 247 Participants |
| Cohort H (PrEP) | Cohort H PrEP Engagement by Study Visit | Week 24 | 224 Participants |
| Cohort H (PrEP) | Cohort H PrEP Engagement by Study Visit | Week 36 | 212 Participants |
| Cohort H (PrEP) | Cohort H PrEP Engagement by Study Visit | Week 48 | 194 Participants |
Other Pre-specified
Escalation in Transmission Risk Behavior Among Participants Reporting Low Risk Behaviors at Baseline
Changes in sexual risk behavior as assessed via CASI-based self-report questionnaire, measured longitudinally over time.
Time frame: Baseline to 48 weeks
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort H (PrEP) | Escalation in Transmission Risk Behavior Among Participants Reporting Low Risk Behaviors at Baseline | High risk reported at baseline and remained high | 278 Participants |
| Cohort H (PrEP) | Escalation in Transmission Risk Behavior Among Participants Reporting Low Risk Behaviors at Baseline | Risk increased from low (baseline) to high | 19 Participants |
| Cohort H (PrEP) | Escalation in Transmission Risk Behavior Among Participants Reporting Low Risk Behaviors at Baseline | Low risk reported at baseline and remained low | 4 Participants |
Other Pre-specified
Number of HIV Seroconversions by Cohort.
Time frame: Baseline to 48 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort H (PrEP) | Number of HIV Seroconversions by Cohort. | 1 Participants |
| Cohort LM (PEP) | Number of HIV Seroconversions by Cohort. | 0 Participants |