Trial Outcomes & Findings for Open Label Extension (OLE) of the TDF2 Study, Botswana (NCT NCT04318210)
NCT ID: NCT04318210
Last Updated: 2022-05-13
Results Overview
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?"
COMPLETED
NA
229 participants
Up to 12 Months
2022-05-13
Participant Flow
Participant milestones
| Measure |
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.
Tenofovir Disoproxil Fumarate 300 mg + Emtricitabine 200 mg
|
|---|---|
|
Overall Study
STARTED
|
229
|
|
Overall Study
COMPLETED
|
153
|
|
Overall Study
NOT COMPLETED
|
76
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Open Label Extension (OLE) of the TDF2 Study, Botswana
Baseline characteristics by cohort
| Measure |
TDF-FTC as PrEP
n=229 Participants
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.
Tenofovir Disoproxil Fumarate 300 mg + Emtricitabine 200 mg
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
229 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
30 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
102 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
127 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black
|
229 Participants
n=5 Participants
|
|
Region of Enrollment
Botswana
|
229 participants
n=5 Participants
|
|
Enrollment Site
Gaborone
|
132 Participants
n=5 Participants
|
|
Enrollment Site
Francistown
|
97 Participants
n=5 Participants
|
|
Education Level
Primary or less
|
4 Participants
n=5 Participants
|
|
Education Level
Secondary
|
141 Participants
n=5 Participants
|
|
Education Level
Post-secondary
|
84 Participants
n=5 Participants
|
|
Marital Status
Single
|
163 Participants
n=5 Participants
|
|
Marital Status
Married
|
18 Participants
n=5 Participants
|
|
Marital Status
Cohabitating
|
37 Participants
n=5 Participants
|
|
Marital Status
Separated/Widowed
|
11 Participants
n=5 Participants
|
|
Employment Status
Employed
|
178 Participants
n=5 Participants
|
|
Employment Status
Unemployed
|
51 Participants
n=5 Participants
|
|
Had an HIV test since TDF2 Study
No
|
17 Participants
n=5 Participants
|
|
Had an HIV test since TDF2 Study
Yes
|
212 Participants
n=5 Participants
|
|
Felt at risk for HIV
No
|
46 Participants
n=5 Participants
|
|
Felt at risk for HIV
Yes
|
183 Participants
n=5 Participants
|
|
Risk from partner for HIV
No
|
73 Participants
n=5 Participants
|
|
Risk from partner for HIV
Yes
|
156 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 12 MonthsA 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?"
Outcome measures
| Measure |
TDF-FTC as PrEP
n=229 Participants
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.
Tenofovir Disoproxil Fumarate 300 mg + Emtricitabine 200 mg
|
|---|---|
|
Self-reported Drug Adherence Over the Past 3 Days
Took daily dosage in past 3 days
|
199 Participants
|
|
Self-reported Drug Adherence Over the Past 3 Days
Took 2 doses in past 3 days
|
9 Participants
|
|
Self-reported Drug Adherence Over the Past 3 Days
Took 1 doses in past 3 days
|
2 Participants
|
|
Self-reported Drug Adherence Over the Past 3 Days
No doses taken in past 3 days
|
19 Participants
|
PRIMARY outcome
Timeframe: Up to 12 monthsPopulation: Among 229 participants, 102 participants were women and 127 participants were men. Analyses were stratified by sex.
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?"
Outcome measures
| Measure |
TDF-FTC as PrEP
n=229 Participants
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.
Tenofovir Disoproxil Fumarate 300 mg + Emtricitabine 200 mg
|
|---|---|
|
Number of Sex Partners
Number of sex partners among women, overall
|
0.87 sexual partners
Standard Deviation 0.53
|
|
Number of Sex Partners
Number of sex partners among men, overall
|
1.03 sexual partners
Standard Deviation 0.74
|
PRIMARY outcome
Timeframe: Up to 12 monthsPopulation: Among 229 participants, 102 participants were women and 127 participants were men. Analyses were stratified by sex.
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?"
Outcome measures
| Measure |
TDF-FTC as PrEP
n=229 Participants
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.
Tenofovir Disoproxil Fumarate 300 mg + Emtricitabine 200 mg
|
|---|---|
|
Number of Sex Acts by Condom Usage
Number of sex acts among women
|
4.01 sex acts
Standard Deviation 5.26
|
|
Number of Sex Acts by Condom Usage
Number of sex acts among men
|
5.95 sex acts
Standard Deviation 6.67
|
|
Number of Sex Acts by Condom Usage
Number of condomless sex acts among women
|
1.28 sex acts
Standard Deviation 3.72
|
|
Number of Sex Acts by Condom Usage
Number of condomless sex acts among men
|
1.70 sex acts
Standard Deviation 4.34
|
|
Number of Sex Acts by Condom Usage
Number of sex acts involving a condom among women
|
2.72 sex acts
Standard Deviation 3.70
|
|
Number of Sex Acts by Condom Usage
Number of sex acts involving a condom among men
|
4.24 sex acts
Standard Deviation 5.19
|
PRIMARY outcome
Timeframe: Up to 12 monthsPopulation: Of 229 participants, 196 participants had monthly DBSs available for analysis over a period of 12 months. These 196 participants contributed a total of 777 monthly DBSs for the TFV extracellular analysis.
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.
Outcome measures
| Measure |
TDF-FTC as PrEP
n=777 Dried spot blood sample
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.
Tenofovir Disoproxil Fumarate 300 mg + Emtricitabine 200 mg
|
|---|---|
|
Extracellular Tenofovir (TFV) for Recent Drug Exposure
Detectable TFV
|
713 number of DBS samples
|
|
Extracellular Tenofovir (TFV) for Recent Drug Exposure
No detectable TFV
|
64 number of DBS samples
|
PRIMARY outcome
Timeframe: Up to 12 monthsPopulation: Of the 196 participants with monthly DBSs available over a period of 12 months, 60 participants were selected for TFV-DP intracellular analysis and contributed a total of 237 monthly DBSs for the TFV-DP intracellular analysis.
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
Outcome measures
| Measure |
TDF-FTC as PrEP
n=237 Dried blood spot sample
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.
Tenofovir Disoproxil Fumarate 300 mg + Emtricitabine 200 mg
|
|---|---|
|
Intracellular Tenofovir-diphosphate (TFV-DP)
7 doses per week
|
141 number of DBS samples
|
|
Intracellular Tenofovir-diphosphate (TFV-DP)
6 doses per week
|
29 number of DBS samples
|
|
Intracellular Tenofovir-diphosphate (TFV-DP)
5 doses per week
|
20 number of DBS samples
|
|
Intracellular Tenofovir-diphosphate (TFV-DP)
4 doses per week
|
6 number of DBS samples
|
|
Intracellular Tenofovir-diphosphate (TFV-DP)
3 doses per week
|
12 number of DBS samples
|
|
Intracellular Tenofovir-diphosphate (TFV-DP)
2 doses per week
|
4 number of DBS samples
|
|
Intracellular Tenofovir-diphosphate (TFV-DP)
1 dose per week
|
5 number of DBS samples
|
|
Intracellular Tenofovir-diphosphate (TFV-DP)
0 doses per week
|
19 number of DBS samples
|
SECONDARY outcome
Timeframe: Up to 12 MonthsStudy 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.
Outcome measures
| Measure |
TDF-FTC as PrEP
n=229 Participants
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.
Tenofovir Disoproxil Fumarate 300 mg + Emtricitabine 200 mg
|
|---|---|
|
HIV Seroconversion
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to 12 MonthsStudy 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.
Outcome measures
| Measure |
TDF-FTC as PrEP
n=229 Participants
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.
Tenofovir Disoproxil Fumarate 300 mg + Emtricitabine 200 mg
|
|---|---|
|
Serious Adverse Events
Hyperamylasemia, Grade 3
|
2 participants
|
|
Serious Adverse Events
Hypophosphatemia, Grade 3
|
5 participants
|
|
Serious Adverse Events
Hypercreatininemia, Grade 1
|
1 participants
|
Adverse Events
TDF-FTC as PrEP
Serious adverse events
| Measure |
TDF-FTC as PrEP
n=229 participants at risk
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.
Tenofovir Disoproxil Fumarate 300 mg + Emtricitabine 200 mg
|
|---|---|
|
Blood and lymphatic system disorders
Hypophosphatemia
|
2.2%
5/229 • Number of events 6 • Adverse event data was collected over the period of 12 months.
|
|
Blood and lymphatic system disorders
Hyperamylasemia
|
0.87%
2/229 • Number of events 2 • Adverse event data was collected over the period of 12 months.
|
|
Renal and urinary disorders
Elevated creatinine
|
0.44%
1/229 • Number of events 1 • Adverse event data was collected over the period of 12 months.
|
Other adverse events
| Measure |
TDF-FTC as PrEP
n=229 participants at risk
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.
Tenofovir Disoproxil Fumarate 300 mg + Emtricitabine 200 mg
|
|---|---|
|
Blood and lymphatic system disorders
Hyperamylasemia
|
55.0%
126/229 • Number of events 223 • Adverse event data was collected over the period of 12 months.
|
|
Blood and lymphatic system disorders
Hypophosphatemia
|
25.3%
58/229 • Number of events 89 • Adverse event data was collected over the period of 12 months.
|
|
Gastrointestinal disorders
Transaminitis
|
9.6%
22/229 • Number of events 26 • Adverse event data was collected over the period of 12 months.
|
|
Blood and lymphatic system disorders
Hyperbilirubinemia
|
7.4%
17/229 • Number of events 23 • Adverse event data was collected over the period of 12 months.
|
|
General disorders
Headache
|
9.2%
21/229 • Number of events 22 • Adverse event data was collected over the period of 12 months.
|
|
Nervous system disorders
Dizziness
|
7.4%
17/229 • Number of events 22 • Adverse event data was collected over the period of 12 months.
|
|
Blood and lymphatic system disorders
Hypocalcemia
|
6.6%
15/229 • Number of events 15 • Adverse event data was collected over the period of 12 months.
|
|
Gastrointestinal disorders
Nausea
|
6.1%
14/229 • Number of events 14 • Adverse event data was collected over the period of 12 months.
|
|
Gastrointestinal disorders
Vomiting
|
5.7%
13/229 • Number of events 13 • Adverse event data was collected over the period of 12 months.
|
|
Gastrointestinal disorders
Pain, abdominal
|
4.8%
11/229 • Number of events 12 • Adverse event data was collected over the period of 12 months.
|
Additional Information
Dr. Allan Taylor
Centers for Disease Control and Prevention
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place