Clinical trial NCT02213328: Acceptability, Safety, and Use of Daily Truvada Pre-Exposure Prophylaxis in Adolescents
Official title: CHAMPS: Choices For Adolescent Prevention Methods For South Africa. Pilot Study B: 'PlusPills'
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2014-08-11
Enrollment: 148
Sex: ALL
Minimum age (years): 15
Maximum age (years): 19
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: Truvada (emtricitabine/tenofovir disoproxil fumarate, or FTC/TDF) is a type of antiretroviral (ARV) medicine that is commonly used to treat HIV. Truvada is also used as pre-exposure prophylaxis (PrEP) to prevent HIV infection in HIV-negative adults. The purpose of this study is to evaluate the acceptability, safety, and use of daily Truvada PrEP as part of a comprehensive HIV prevention package in healthy, HIV-uninfected adolescents 15 to 19 years of age.

Detailed description: Truvada PrEP is an approach used to protect HIV-uninfected adults against possible infection with HIV. The approach involves taking Truvada every day to prevent HIV infection in case the person is exposed to HIV (for example, through sex with an HIV-infected person). The purpose of this study is to evaluate the acceptability, safety, and use of daily Truvada PrEP as part of a comprehensive HIV prevention package in healthy, HIV-uninfected adolescents 15 to 19 years old. In addition to Truvada PrEP, the HIV prevention package will include HIV testing, management of sexually transmitted infections (STIs), risk reduction counseling, access to condoms, post-exposure prophylaxis (PEP), and circumcision counseling and referral for male participants.

The study will enroll 150 healthy, HIV-uninfected adolescents 15 to 19 years of age. The study will last for 12 months (52 weeks) and involve scheduled clinic visits at study entry (Week 0) and Weeks 4, 8, 12, 24, 36, 48, and 52.

For the first 12 weeks of the study, all participants will be provided with a supply of Truvada tablets to take once daily as part of the comprehensive HIV prevention package. At Weeks 12, 24, 36, and 48, participants will be offered the following options: to continue with the full HIV prevention package plus Truvada PrEP, to stop Truvada PrEP and continue with rest of the HIV prevention package, or to re-start Truvada PrEP if previously stopped. After Week 12 of the study, Truvada tablets will be given only to those participants who decide to take PrEP and who do not have any medical reasons not to do so. Regardless whether they choose to use Truvada PrEP after Week 12, all study participants will be followed through Week 52 of the study.

All study visits will include blood collection, counseling before and after HIV testing, urine collection for pregnancy testing (female participants only), completion of a sexual risk behavior questionnaire, receipt of a supply of condoms, contraceptive counseling, a medical history review, and disclosure of available test results. Select study visits may include a physical exam, blood and urine collection, testing and treatment of STIs, adherence counseling, and an acceptability assessment. Between Months 11 and 12 of the study, some participants will be randomly selected to participate in focus groups to discuss their experiences while taking Truvada PrEP.

Eligibility criteria: Inclusion Criteria:

* Age 15 to 19 years (inclusive) at screening, verified per study site standard operating procedures (SOPs)
* Able and willing to provide written informed consent/assent (age dependent) to be screened for and to take part in the study
* Have a guardian who is able and willing to provide written informed consent for his or her child to be screened for and to take part in the study
* Able and willing to provide adequate locator information, as defined in site standard operating procedures (SOPs)
* HIV-uninfected based on testing performed by study staff at screening and enrollment
* Sexually active, as defined as a minimum of one act of (penile vaginal) sexual intercourse in the last 12 months, per self-report
* (For female participants) Negative pregnancy test at screening and enrollment and, per participant report, does not intend to become pregnant in the next 12 months
* (For female participants) Using an effective method of contraception at enrollment, and intending to use an effective method for the study duration; effective methods include low dose oral, implant, or injectable hormonal methods.
* Does not report intention to relocate out of the study area during the course of the study
* Does not have job or other obligations that would require long absences from the area (for more than 4 weeks at a time)
* Willing to undergo all study-required procedures
* At screening and enrollment, agrees not to participate in other research studies involving drugs or medical devices for the next 12 months

Exclusion Criteria:

Participants who meet any of the following criteria, at baseline, are excluded from the study:

* As determined by the Site Investigator, any significant uncontrolled active or chronic disease process such as but not limited to diabetes, hypertension, and other diseases involving the cardiovascular, pulmonary, gastrointestinal, genitourinary, musculoskeletal, and central nervous systems
* Confirmed Grade 2 or greater hypophosphatemia
* Presence of serious psychiatric symptoms (e.g., active hallucinations)
* Visibly distraught at the time of consent (e.g., suicidal, homicidal, exhibiting violent behavior)
* Intoxicated or under the influence of alcohol or other drugs at the time of consent
* Acute or chronic hepatitis B infection (i.e., if hepatitis B surface antigen positive)
* Hepatitis B seronegative and refuses vaccination
* Renal dysfunction (creatinine clearance less than 75 ml/min); Use Cockroft-Gault equation as detailed in the protocol
* Urine dipstick for protein and glucose, excluding values of "1 +" or greater
* Any history of bone fractures not explained by trauma
* Any Grade 2 or greater toxicity on screening tests and assessments
* Concurrent participation in an HIV vaccine study or other investigational drug study
* Known allergy/sensitivity to the study drug or its components
* Use of disallowed medications (as detailed in the protocol)

Primary outcomes:
measure: The Percentage of Participants Who Report Willingness to Use the Study Regimen, Take up PrEP, and Remain on PrEP as Part of a Comprehensive Prevention Package
timeFrame: Measured through Week 48
measure: Number of Participants With Acceptability as Per Questionnaire Administered at Week 48
timeFrame: Measured at Week 48
measure: Number of Adolescents Who Continue to Use PrEP (as Indicated by Dried Blood Spot [DBS] Levels) After the Initial 3-month Period
timeFrame: Measured through Week 48
measure: Number of Participants With Grades 2, 3, and 4 Clinical and Laboratory Adverse Events
timeFrame: Measured through Week 48
measure: Number of Adolescents Enrolled and Retained in the Study
timeFrame: Measured through Week 52
Secondary outcomes:
measure: Number of Participants Who Used PrEP at Any Time Point During the Study, Measured With Drug Levels at M4/8/12/24/36
timeFrame: Measured through Week 48
measure: Proportion of Adolescents With Detectable Drug Levels Who Report Using PrEP
timeFrame: Measured though Week 48
measure: Number of Participants Reporting Multiple Partners in the Preceding Year as Evidenced by Participant Responses to Interviewer Administered Questionnaires at Enrolment
timeFrame: Baseline
measure: Reported Consistent Condom Use as Evidenced by Participant Responses to Interviewer-administered Questionnaires Adminstered at the Enrolment Visit
timeFrame: Baseline
measure: Reported Alcohol and Substance Use as Evidenced by Participant Responses to Interviewer-administered Questionnaires at the Enrolment Visit
timeFrame: Baseline visit
measure: Percentage of Study Participants Who Seroconverted During the Study, Measured Until Month 52
timeFrame: Measured through Week 52
Other outcomes:
Locations:
city: Cape Town
country: South Africa
facility: Desmond Tutu HIV Foundation Non-Network CRS
city: Soweto
country: South Africa
facility: Perinatal HIV Non-network Research CRS
Study officials:
affiliation: Desmond Tutu HIV Centre
name: Linda-Gail Bekker, MBChB, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gill K, Johnson L, Dietrich J, Myer L, Marcus R, Wallace M, Pidwell T, Mendel E, Fynn L, Jones K, Wiesner L, Slack C, Strode A, Spiegel H, Hosek S, Rooney J, Gray G, Bekker LG. Acceptability, safety, and patterns of use of oral tenofovir disoproxil fumarate and emtricitabine for HIV pre-exposure prophylaxis in South African adolescents: an open-label single-arm phase 2 trial. Lancet Child Adolesc Health. 2020 Dec;4(12):875-883. doi: 10.1016/S2352-4642(20)30248-0. Epub 2020 Oct 24.