- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04318210
Open Label Extension (OLE) of the TDF2 Study, Botswana (TDF2-OLE)
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 Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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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.
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Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Self-reported Drug Adherence Over the Past 3 Days
Time Frame: Up to 12 Months
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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
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Number of Sex Partners
Time Frame: Up to 12 months
|
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
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Number of Sex Acts by Condom Usage
Time Frame: Up to 12 months
|
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
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Extracellular Tenofovir (TFV) for Recent Drug Exposure
Time Frame: Up to 12 months
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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
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Intracellular Tenofovir-diphosphate (TFV-DP)
Time Frame: Up to 12 months
|
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
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Up to 12 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
HIV Seroconversion
Time Frame: Up to 12 Months
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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.
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Up to 12 Months
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Serious Adverse Events
Time Frame: Up to 12 Months
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Study visits were scheduled every month until study completion.
Participants were instructed to return to the clinic for evaluation in event of illness.
Participants reported any adverse effects (AEs) at monthly or interim visits and were determined as serious adverse events (SAE) when at least possibly related to study drug.
DAIDS Table for Grading Severity of Adult Adverse Experiences for Vaccine & Prevention Research Programs was used for grading.
Definitions: Grade 3-'probably related'-strong temporal relationship to study product that cannot be explained by participant's clinical state or other factors and a causal relationship is biologically plausible.
Grade 4-'definitely related'-distinct temporal relationship to administration of the study product that cannot be explained by the participant's clinical state or other factors or AE occurs on re-challenge or the AE is a known reaction to the product or chemical group or can be predicted by the product's pharmacology.
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Up to 12 Months
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Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Allan Taylor, MD, MPH, Centers for Disease Control and Prevention
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- RNA Virus Infections
- Virus Diseases
- Blood-Borne Infections
- Communicable Diseases
- Sexually Transmitted Diseases, Viral
- Sexually Transmitted Diseases
- Lentivirus Infections
- Retroviridae Infections
- Immunologic Deficiency Syndromes
- Immune System Diseases
- Slow Virus Diseases
- HIV Infections
- Infections
- Acquired Immunodeficiency Syndrome
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Reverse Transcriptase Inhibitors
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Anti-HIV Agents
- Anti-Retroviral Agents
- Tenofovir
- Emtricitabine
Other Study ID Numbers
- CDC-NCHHSTP-4940-1
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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