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

NCT04318210 | Completed Results

• 1 other identifier: CDC-NCHHSTP-4940-1
• Study Type: interventional
• Target: 229
• Locations: 0 countries
• Sites: N/A

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.

Conditions

HIV Infections

Keywords

HIV incidence; HIV prevention; Tenofovir; Emtricitabine; Botswana; HIV seronegativity; PrEP

Outcome Measures

Primary Outcomes (5)

• Self-reported Drug Adherence Over the Past 3 Days

  A 30-day supply of TDF/FTC was dispensed at each monthly visit, for up to 12 months. Participants were asked monthly about their drug adherence and were asked to recall their time of dosing over the past 3 days. Question: "Please think back to \[yesterday, 2 days ago, 3 days ago\]. What time did you take Truvada? Was it in the morning, afternoon, evening, or you weren't able to take the pill that day?"

  Up to 12 Months

• Number of Sex Partners

  Number of sex partners was assessed at baseline and each scheduled monthly visit, for up to 12 months. Responses to the following question refers to the number of partners reported in the past 30 days: "In the past 30 days, with how many partners have you had sexual intercourse?"

  Up to 12 months

• Number of Sex Acts by Condom Usage

  Number of sex acts by condom usage was assessed at baseline and each scheduled monthly visit, for up to 12 months. Responses to the following question refers to the number of sex acts with up to 3 partners. "In the past 30 days, how many times did you have sex with \['this partner'\]? When I ask about the number of times you had sex, please count each sexual act. For example, if you had 2 rounds of sexual intercourse with your partner on a single evening, count that as two times you had sex. Please remember that this only refers to vaginal and anal sex. It does not refer to oral sex." To assess condom use by sex act, the following question was asked to assess the number of sex acts with condoms and without condoms with up to 3 partners: "Of the \_\_\_ sex acts, how many times did you not use condoms the entire time?"

  Up to 12 months

• Extracellular Tenofovir (TFV) for Recent Drug Exposure

  Dried blood spots were collected at each monthly study visit to characterize drug adherence by measuring extracellular tenofovir (TFV) for recent drug exposure (\~24 hours). Of 229 participants, 196 participants had monthly DBSs available for analysis. A sampling algorithm was designed to make inference to TFV and TFV-DP levels at all 12 months. For the TFV extracellular analysis, participants were randomly assigned to one of three sampling schedules, with equal probability: (a) months 1, 2, 5, 8, and 11; (b) months 1, 3, 6, 9, and 12; and (c) months 1, 4, 7, 10, and 12. These 196 participants contributed a total of 777 monthly DBSs for the TFV extracellular analysis. Extracellular TFV detectability was defined as having a mean TFV level (of up to four measurements) equal to or greater than 5 ng/mL.

  Up to 12 months

• Intracellular Tenofovir-diphosphate (TFV-DP)

  Dried blood spots were collected at each monthly study visit to characterize drug adherence by measuring intracellular tenofovir-diphosphate (TFV-DP) for long-term drug exposure (\~7 days). The 196 participants who had monthly DBSs available were stratified by site, gender, and the 3 patterns previously assigned for the TFV extracellular analysis (2×2×3 = 12 strata). Then 60 participants were selected, 5 from each of the 12 strata, to balance by site, gender, and the above 3 patterns were maintained. In turn, the monthly DBSs indicated by the assigned pattern were analyzed. These 60 participants contributed a total of 237 monthly DBSs for the TFV-DP intracellular analysis. The observed TFV-DP levels in our study population were categorized as follows (units of drug in fmol/mL): 0 doses per week (\<912); 1 dose taken per week (≥912 and \<1824); 2 doses taken per week (≥1824 and \<2688); 3 doses taken per week (≥2688 and \<3600); 4 doses taken per week (≥3600 and \<4464); 5 to 7 doses taken

  Up to 12 months

Secondary Outcomes (2)

• HIV Seroconversion

  Up to 12 Months

• Serious Adverse Events

  Up to 12 Months

Study Arms (1)

TDF-FTC as PrEP

EXPERIMENTAL

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

Interventions

Tenofovir Disoproxil Fumarate 300 mg + Emtricitabine 200 mg DRUG

Also known as: Truvada

TDF-FTC as PrEP

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Centers for Disease Control and Prevention: lead
• Botswana Ministry of Health: collaborator

MeSH Terms

Conditions

HIV Infections

Interventions

Tenofovir; Emtricitabine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: Dr. Allan Taylor
• Organization: Centers for Disease Control and Prevention

avt0@cdc.gov

404-639-6120

Study Officials

• Allan Taylor, MD, MPH

  Centers for Disease Control and Prevention

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 3, 2020
• First Posted: March 23, 2020
• Study Start: October 1, 2012
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: May 13, 2022
• Results First Posted: May 13, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share