Clinical trial NCT04318210: Open Label Extension (OLE) of the TDF2 Study, Botswana
Official title: Open Label Extension (OLE) of the Study of the Safety and Efficacy of Daily Oral Antiretroviral Use for the Prevention of HIV Infection in Heterosexually Active Young Adults in Botswana
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV Infections
Keywords: HIV incidence
HIV prevention
Tenofovir
Emtricitabine
Botswana
HIV seronegativity
PrEP
Lead sponsor: Centers for Disease Control and Prevention
Sponsor class: FED
Collaborators: name: Botswana Ministry of Health
First posted: 2020-03-23
Enrollment: 229
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: This study is an open label and is an extension to the TDF2 study in which the investigators offered daily oral tenofovir/emtricitabine (TDF/FTC) for a maximum of 12 months to HIV uninfected former participants of the TDF2 study.

Detailed description: This open label phase builds on a unique opportunity provided by the end of the randomized phase of the TDF 2 study. The randomized study provided a well-characterized cohort of persons who received standard prevention interventions, including monthly testing, counseling, and condoms. The primary intervention that will change in the open label phase is the provision of information about the demonstrated efficacy and safety of PrEP including counseling about how PrEP is not 100% effective, provision of open label rather than blinded study medication, and a shortened visit schedule designed to more closely approximate what would be feasible in an implementation program. This open label phase will therefore serve as an opportunity to gather additional information relevant to the delivery and uptake of daily oral PrEP that may help inform eventual more wide scale PrEP implementation in Botswana.The OLE also leverages unique opportunities to address important questions about how information about PrEP safety and efficacy might affect risk behavior. The randomized trial showed that condom use (81.9% in the TDF/FTC group and 79.7% in the placebo group, p = 0.21) and the number of participants with more than one sexual partner in the previous month (14.2% in the TDF/FTC group and 14.1% in the placebo group, p = 0.86) between the two groups was similar. The underlying premise of this OLE is that information about PrEP efficacy and the knowledge of taking active drug rather than placebo might alter perception of HIV risk. This extension seeks to determine whether this trend will occur in the cohort after individuals receive information and counseling about the partial protective efficacy of PrEP and to identify risk factors for changes in risk behavior. The randomized trial revealed that reported drug adherence between the two arms was almost identical at 84.1% in the TDF/FTC group and 83.7% in the placebo arm (p = 0.79). The investigators have designed this open label phase in order to determine 1) if the knowledge of receiving active drug and the receipt of information about PrEP safety and partial efficacy at the onset of the open label phase could have substantial effects on pill use and 2) to identify individual factors associated with this impact. In addition, the open label extension will provide more information about the long term safety of Truvada.

Eligibility criteria: Inclusion Criteria:

* Former TDF 2 participants
* Willing and able to provide informed written consent for participation
* If female, willing to use effective contraception during the trial (oral or injectable hormonal contraception, an intrauterine device \[IUD\], or who have had surgical interventions such as bilateral tubal ligation or hysterectomy)
* Laboratory values as follows within 30 days prior to enrollment:
* HIV uninfected by dual, parallel, rapid whole blood testing and HIV EIA
* Serum phosphorus ≥ 2.2 mg/dL
* Calculated creatinine clearance ≥ 60 mL/min

Exclusion Criteria:

* Positive urine pregnancy test (females)
* Breastfeeding (females)
* History of significant renal or bone disease
* Any other clinical condition or prior therapy that, in the opinion of the physician would make the subject unsuitable for the OLE or unable to comply with the dosing requirements

Primary outcomes:
measure: Self-reported Drug Adherence Over the Past 3 Days
timeFrame: Up to 12 Months
measure: Number of Sex Partners
timeFrame: Up to 12 months
measure: Number of Sex Acts by Condom Usage
timeFrame: Up to 12 months
measure: Extracellular Tenofovir (TFV) for Recent Drug Exposure
timeFrame: Up to 12 months
measure: Intracellular Tenofovir-diphosphate (TFV-DP)
timeFrame: Up to 12 months
Secondary outcomes:
measure: HIV Seroconversion
timeFrame: Up to 12 Months
measure: Serious Adverse Events
timeFrame: Up to 12 Months
Other outcomes:
Locations:
Study officials:
affiliation: Centers for Disease Control and Prevention
name: Allan Taylor, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: