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Open Label Extension (OLE) of the TDF2 Study, Botswana (TDF2-OLE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT04318210
Recruitment Status : Completed
First Posted : March 23, 2020
Last Update Posted : March 23, 2020
Botswana Ministry of Health
Information provided by (Responsible Party):
Centers for Disease Control and 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.

Condition or disease Intervention/treatment Phase
HIV Infections Drug: Tenofovir Disoproxil Fumarate 300 mg + Emtricitabine 200 mg Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 229 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
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
Actual Study Start Date : October 2012
Actual Primary Completion Date : July 2014
Actual Study Completion Date : July 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: TDF-FTC as PrEP
Eligible HIV-uninfected participants were offered 12 months of oral Tenofovir Disoproxil Fumarate 300 mg + Emtricitabine 200 mg (TDF-FTC) once daily in the form of a single tablet regardless of their original study assignment in randomized phase.
Drug: Tenofovir Disoproxil Fumarate 300 mg + Emtricitabine 200 mg
Other Name: Truvada

Primary Outcome Measures :
  1. Drug adherence [ Time Frame: Up to 12 Months ]
    A 30-day supply of TDF/FTC was dispensed at each monthly visit, for up to 12 months. Unused pills were retrieved and counted by study staff. Self-reported adherence measurements included a 3-day recall and a self-assessment scale (e.g., poor, fair, good, very good) to describe the overall adherence experienced in the past 30 days. DBSs were collected at each monthly study visit to characterize drug adherence by measuring extracellular tenofovir (TFV) for recent drug exposure and intracellular tenofovir-diphosphate (TFV-DP) for long-term drug exposure.

  2. Sexual behavior [ Time Frame: Up to 12 Months ]
    Sexual behavior was assessed at each scheduled monthly visit, for up to 12 months. Monthly sexual behavior questions included assessment of number of sexual partners, number of sex acts, and condom usage. HIV risk perception was assessed at study enrollment, month 6 and month 12. Perceived past risk was defined as feeling at risk for HIV in the past 6 months, whereas perceived future risk was defined as feeling at risk for HIV in the next 6 months, using a scale of high risk, medium risk, and low or no risk.

Secondary Outcome Measures :
  1. HIV Seroconversion [ Time Frame: Up to 12 Months ]
    Study visits were scheduled every month until completion of the study and during monthly study visits, HIV testing was performed, for up to 12 months. During monthly visits, routine HIV testing was performed with two HIV rapid tests. If HIV-infection was suspected, HIV antigen-antibody (Ag/Ab) combination enzyme immunoassay (EIA) (Bio-Rad, GS HIV Combo Ag/Ab EIA) testing was performed, and RNA viral load was measured.

  2. Adverse events [ Time Frame: Up to 12 Months ]
    Study visits were scheduled every month until completion of the study (up to 12 months), and participants were instructed to return to the clinic for evaluation in the event of an illness. Participants reported any adverse effects at monthly visits and interim visits.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 64 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04318210

Sponsors and Collaborators
Centers for Disease Control and Prevention
Botswana Ministry of Health
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Principal Investigator: Allan Taylor, MD, MPH Centers for Disease Control and Prevention
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Responsible Party: Centers for Disease Control and Prevention Identifier: NCT04318210    
Other Study ID Numbers: CDC-NCHHSTP-4940-1
First Posted: March 23, 2020    Key Record Dates
Last Update Posted: March 23, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Data cannot be shared publicly without permission from the country of Botswana but may be available upon request.
Keywords provided by Centers for Disease Control and Prevention:
HIV incidence
HIV prevention
HIV seronegativity
Additional relevant MeSH terms:
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HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents