HIV InfectionsTDF2-OLENCT04318210
Open Label Extension (OLE) of the TDF2 Study, Botswana
A study testing Tenofovir Disoproxil Fumarate 300 mg + Emtricitabine 200 mg in people with HIV Infections, run by Centers for Disease Control and Prevention.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 64 yearsHealthy volunteers can take part
- Conditions the study is for
- HIV Infections
- What is being tested?
- Tenofovir Disoproxil Fumarate 300 mg + Emtricitabine 200 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 229 participants
- Where
- No sites listed yet
- Study dates
- Oct 2012to Jul 2014
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 64 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
About this study
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
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.
Read the 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.
- Conditions
- HIV Infections
- Being tested
- Tenofovir Disoproxil Fumarate 300 mg + Emtricitabine 200 mg
- Keywords
- HIV incidence, HIV prevention, Tenofovir, Emtricitabine, Botswana, HIV seronegativity, PrEP
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tenofovir Disoproxil Fumarate 300 mg + Emtricitabine 200 mgDrug
Also called Truvada
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Tenofovir Disoproxil Fumarate 300 mg + Emtricitabine 200 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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?"
Measured: 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?"
Measured: 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?"
Measured: 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.
Measured: 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
Measured: Up to 12 months
Secondary outcomes (2)
HIV Seroconversion
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.
Measured: Up to 12 Months
Serious Adverse Events
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.
Measured: Up to 12 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Mar 2020
- Study startOct 2012
- Primary completionJul 2014
- Study completionJul 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 229 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centers for Disease Control and Prevention
- Sponsor type
- US federal agency
- Collaborators
- Botswana Ministry of Health
- Responsible party
- Sponsor
- Investigators
- Allan Taylor, MD, MPH, Principal investigator, Centers for Disease Control and Prevention
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04318210
- Sponsor's protocol ID
- CDC-NCHHSTP-4940-1
- Acronym
- TDF2-OLE
- Status last verified
- May 2022
- First submitted
- 3 Mar 2020
- Last updated
- 13 May 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No: Data cannot be shared publicly without permission from the country of Botswana but may be available upon request.
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04318210
- Acronym / sponsor ID
- TDF2-OLE / CDC-NCHHSTP-4940-1
- Conditions
- HIV Infections
- Keywords
- HIV incidence, HIV prevention, Tenofovir, Emtricitabine, Botswana, HIV seronegativity, PrEP
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 229 participants (actual)
- Lead sponsor
- Centers for Disease Control and PreventionUS federal agency
- Collaborators
- Botswana Ministry of Health
- Study start
- Oct 2012 (actual)
- Primary completion
- Jul 2014 (actual)
- Study completion
- Jul 2014 (actual)
- First posted
- 23 Mar 2020 (actual)
- Results
- Posted 13 May 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TDF-FTC as PrEP | Experimental | Drug: Tenofovir Disoproxil Fumarate 300 mg + Emtricitabine 200 mgEligible 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. |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tenofovir Disoproxil Fumarate 300 mg + Emtricitabine 200 mgAlso: Truvada | Drug | TDF-FTC as PrEP |
Primary outcome
Self-reported Drug Adherence Over the Past 3 Days
Time frame: Up to 12 Months
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?"
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?"
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?"
Extracellular Tenofovir (TFV) for Recent Drug Exposure
Time frame: Up to 12 months
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.
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
2 secondary outcomes
HIV Seroconversion
Time frame: Up to 12 Months
Serious Adverse Events
Time frame: Up to 12 Months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. Data cannot be shared publicly without permission from the country of Botswana but may be available upon request.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Allan Taylor, MD, MPH principal investigator
Centers for Disease Control and Prevention
Questions about this trial
What is this clinical trial studying?
A study testing Tenofovir Disoproxil Fumarate 300 mg + Emtricitabine 200 mg in people with HIV Infections, run by Centers for Disease Control and Prevention.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 May 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 May 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Self-reported Drug Adherence Over the Past 3 Days (time frame: Up to 12 Months). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2022.