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Emtricitabine/Tenofovir Disoproxil Fumarate for HIV Prevention in Men (iPrEx)

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.
ClinicalTrials.gov Identifier: NCT00458393
Recruitment Status : Completed
First Posted : April 10, 2007
Results First Posted : January 24, 2018
Last Update Posted : January 24, 2018
Sponsor:
Collaborator:
Bill and Melinda Gates Foundation
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Prevention
Condition HIV Infections
Interventions Drug: daily TDF/FTC
Drug: Placebo
Enrollment 2499
Recruitment Details The study recruited HIV uninfected participants whose sexual practices put them at risk for HIV infection. They were recruited from community clinics.
Pre-assignment Details  
Arm/Group Title TDF/FTC Placebo
Hide Arm/Group Description

Daily oral emtricitabine/tenofovir disoproxil fumarate

Emtricitabine/tenofovir disoproxil fumarate: Fixed-dose coformulation of 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate

Daily oral placebo

Placebo: Placebo for emtricitabine/tenofovir disoproxil fumarate

Period Title: Overall Study
Started 1251 1248
Completed 942 953
Not Completed 309 295
Reason Not Completed
Withdrawal by Subject             67             80
Physician Decision             31             22
Relocated             77             81
Lost to Follow-up             115             92
Sites marked other on the form.             19             20
Arm/Group Title TDF/FTC Placebo Total
Hide Arm/Group Description

Daily oral emtricitabine/tenofovir disoproxil fumarate

Emtricitabine/tenofovir disoproxil fumarate: Fixed-dose coformulation of 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate

Daily oral placebo

Placebo: Placebo for emtricitabine/tenofovir disoproxil fumarate

Total of all reporting groups
Overall Number of Baseline Participants 1251 1248 2499
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1251 participants 1248 participants 2499 participants
<=18 years
92
   7.4%
101
   8.1%
193
   7.7%
Between 18 and 65 years
1158
  92.6%
1147
  91.9%
2305
  92.2%
>=65 years
1
   0.1%
0
   0.0%
1
   0.0%
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 1251 participants 1248 participants 2499 participants
25
(18 to 67)
24
(18 to 63)
24
(18 to 67)
Sex/Gender, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1251 participants 1248 participants 2499 participants
Male Sex at Birth. Identify Trans
155
  12.4%
155
  12.4%
310
  12.4%
Male Sex at Birth. Identify Female
15
   1.2%
14
   1.1%
29
   1.2%
Male Sex at Birth. Identify Male
1081
  86.4%
1079
  86.5%
2160
  86.4%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 1251 participants 1248 participants 2499 participants
Ecuador 150 150 300
United States 113 114 227
Brazil 186 184 370
South Africa 45 43 88
Thailand 57 57 114
Peru 700 700 1400
1.Primary Outcome
Title HIV Seroconversion
Hide Description Confirmed HIV infection
Time Frame Monthly follow-up through a median of 1.2 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Excludes participants who were HIV+ at enrollment (2 TDF/FTC, 8 Placebo) and those with no follow-up HIV test (25 TDF/FTC and 22 Placebo).
Arm/Group Title TDF/FTC Placebo
Hide Arm/Group Description:

Daily oral emtricitabine/tenofovir disoproxil fumarate

Emtricitabine/tenofovir disoproxil fumarate: Fixed-dose coformulation of 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate

Daily oral placebo

Placebo: Placebo for emtricitabine/tenofovir disoproxil fumarate

Overall Number of Participants Analyzed 1224 1218
Measure Type: Count of Participants
Unit of Measure: Participants
48
   3.9%
83
   6.8%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TDF/FTC, Placebo
Comments Primary null hypothesis: Relative hazard of 0.7 or less. Secondary null hypothesis: Relative hazard of 1.0 or less.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments secondary p-value given.
Method Log Rank
Comments stratified by site
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.577
Confidence Interval (2-Sided) 95%
.404 to .824
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.105
Estimation Comments Efron correction for ties. Placebo is reference. Results typically quoted as efficacy = 100*(1-HR)
2.Primary Outcome
Title Grade 1 or Higher Creatinine Toxicity
Hide Description Creatinine which reach grade 1 (mild, 1.1 to 1.3 local upper limit of normal) or higher by the US Division of AIDS grading table (version 1) or a 50% increase in creatinine from the baseline value. The DAIDS table can be found at https://rsc.tech-res.com/docs/default-source/safety/table_for_grading_severity_of_adult_pediatric_adverse_events.pdf
Time Frame Duration of follow-up, median 1.2 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants which at least 1 follow-up creatinine value
Arm/Group Title TDF/FTC Placebo
Hide Arm/Group Description:
Daily oral emtricitabine/tenofovir disoproxil fumarate
Daily oral placebo
Overall Number of Participants Analyzed 1216 1217
Measure Type: Count of Participants
Unit of Measure: Participants
32
   2.6%
24
   2.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TDF/FTC, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.28
Comments p-value is not adjusted for multiple comparisons, a priori threshold for statistical significance was p < 0.05
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.33
Confidence Interval (2-Sided) 95%
0.79 to 2.25
Estimation Comments [Not Specified]
3.Primary Outcome
Title Grade 3 or Higher Phosphorous Toxicity
Hide Description Grade 3 or higher phosphorous toxicity (hypophosphatemia) by the Division of AIDS Grading Table (severe, level at or below 1.9 mg/dL)
Time Frame The entire follow-up period, median 1.2 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants with at least 1 follow-up phosphorus value
Arm/Group Title TDF/FTC Placebo
Hide Arm/Group Description:
Daily oral emtricitabine/tenofovir disoproxil fumarate
Daily oral placebo
Overall Number of Participants Analyzed 1225 1226
Measure Type: Count of Participants
Unit of Measure: Participants
13
   1.1%
10
   0.8%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TDF/FTC, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.54
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.3
Confidence Interval (2-Sided) 95%
.57 to 2.96
Estimation Comments [Not Specified]
4.Primary Outcome
Title Grade 2, 3, or 4 Laboratory Adverse Events
Hide Description Number of participants with at least one Grade 2, 3, or 4 laboratory adverse events (moderate, severe of life threatening based one the US Division of AIDS Grading of adverse events, version 1.0). The table can be found at https://rsc.tech-res.com/docs/default-source/safety/table_for_grading_severity_of_adult_pediatric_adverse_events.pdf
Time Frame Entire follow-up, median 1.2 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
At participants with at least one visit with laboratory values post-baseline
Arm/Group Title TDF/FTC Placebo
Hide Arm/Group Description:
Daily oral emtricitabine/tenofovir disoproxil fumarate
Daily oral placebo
Overall Number of Participants Analyzed 1229 1226
Measure Type: Count of Participants
Unit of Measure: Participants
70
   5.7%
79
   6.4%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TDF/FTC, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.50
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.89
Confidence Interval (2-Sided) 95%
0.65 to 1.23
Estimation Comments [Not Specified]
5.Primary Outcome
Title Grade 2, 3, or 4 Clinical Adverse Events
Hide Description Number of participants with at least 1 Grade 2, 3, or 4 clinical adverse events (moderate, severe of life threatening based one the US Division of AIDS Grading of adverse events, version 1.0). The table can be found at https://rsc.tech-res.com/docs/default-source/safety/table_for_grading_severity_of_adult_pediatric_adverse_events.pdf
Time Frame Entire follow-up, median 1.2 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
At participants with at least one follow-up visit
Arm/Group Title TDF/FTC Placebo
Hide Arm/Group Description:
Daily oral emtricitabine/tenofovir disoproxil fumarate
Daily oral placebo
Overall Number of Participants Analyzed 1226 1230
Measure Type: Count of Participants
Unit of Measure: Participants
157
  12.8%
162
  13.2%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TDF/FTC, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.92
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.99
Confidence Interval (2-Sided) 95%
0.79 to 1.23
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Hepatitis Flares Among Hepatitis B Virus (HBV) Infected Persons During and After Chemoprophylaxis
Hide Description

A hepatic flare is defined as an increase in alanine transaminase or aspartate transaminase to >5 fold upper limit of normal at any visit, or an increase to >2.5 fold upper limit of normal for 3 months, within 24 weeks of permanently stopping study drug.

More details in https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4752387/

Time Frame Quarterly lab tests through a median follow-up of 1.2 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Those with chronic active hepatitis B at enrollment.
Arm/Group Title TDF/FTC Placebo
Hide Arm/Group Description:

Daily oral emtricitabine/tenofovir disoproxil fumarate

Emtricitabine/tenofovir disoproxil fumarate: Fixed-dose coformulation of 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate

Daily oral placebo

Placebo: Placebo for emtricitabine/tenofovir disoproxil fumarate

Overall Number of Participants Analyzed 6 6
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TDF/FTC, Placebo
Comments Null hypothesis of no difference
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.00
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection TDF/FTC, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Desc
Statistical Test of Hypothesis P-Value 1.00
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 0.00
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Percentage Change in Bone Mineral Density
Hide Description % Change from baseline in bone mineral density (100 * [(value at 24 weeks- value at baseline)/ (value at baseline)]) in in hip and L1-L4 spine by dual-energy x-ray absorptiometry
Time Frame baseline and week 24.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants confirmed to be HIV negative at enrollment who consented to participate in the metabolic substudy. Full details in https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25908682/
Arm/Group Title TDF/FTC Placebo
Hide Arm/Group Description:

Daily oral emtricitabine/tenofovir disoproxil fumarate

Emtricitabine/tenofovir disoproxil fumarate: Fixed-dose coformulation of 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate

Daily oral placebo

Placebo: Placebo for emtricitabine/tenofovir disoproxil fumarate

Overall Number of Participants Analyzed 210 211
Mean (Standard Error)
Unit of Measure: percent change from baseline
L1-L4 Spine bone mineral density -0.59  (0.21) 0.32  (0.21)
Hip bone mineral density -0.34  (0.16) 0.29  (0.16)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TDF/FTC, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments < 0.05 for statistical significance. no adjustment for multiple comparisons
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -.91
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Percentage Change in Body Fat
Hide Description Percentage Change (100 * [(value at 24 weeks- value at baseline)/ (value at baseline)]) in Body Fat from Baseline by dual-energy x-ray absorptiometry
Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants in the body composition substudy who made a week 24 body scan
Arm/Group Title TDF/FTC Placebo
Hide Arm/Group Description:
Daily oral emtricitabine/tenofovir disoproxil fumarate
Daily oral placebo
Overall Number of Participants Analyzed 210 211
Median (Standard Error)
Unit of Measure: percent change from baseline
0.0  (1.0) 3.8  (1.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TDF/FTC, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.009
Comments [Not Specified]
Method median regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value -3.8
Confidence Interval (2-Sided) 95%
-6.6 to -0.95
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Percentage Change in Fasting Triglycerides
Hide Description Percentage Change (Percentage Change (100 * [(value at 24 weeks- value at baseline)/ (value at baseline)]) in Triglycerides from Baseline from a fasting sample.
Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants in the metabolic substudy with a week 24 fast triglyceride value
Arm/Group Title TDF/FTC Placebo
Hide Arm/Group Description:
Daily oral emtricitabine/tenofovir disoproxil fumarate
Daily oral placebo
Overall Number of Participants Analyzed 199 194
Median (Standard Error)
Unit of Measure: percent change from baseline
0.0  (3.3) 0.0  (3.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TDF/FTC, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.00
Comments [Not Specified]
Method median regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-9.3 to 9.3
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Percent Change in Total Cholesterol
Hide Description Percent change (100 * [(value at 24 weeks- value at baseline)/ (value at baseline)]) in fasting total cholesterol from baseline
Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants in the metabolic substudy with a week 24 fasting cholesterol
Arm/Group Title TDF/FTC Placebo
Hide Arm/Group Description:
Daily oral emtricitabine/tenofovir disoproxil fumarate
Daily oral placebo
Overall Number of Participants Analyzed 199 194
Median (Standard Error)
Unit of Measure: percent change from baseline
-3.2  (1.2) -1.1  (1.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TDF/FTC, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.19
Comments [Not Specified]
Method median regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value -2.2
Confidence Interval (2-Sided) 95%
-5.5 to 1.1
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Viral Load Among HIV Infected Participants
Hide Description HIV-RNA in log10 units among HIV infected participants at the time closest to HIV detection
Time Frame At the time closest to HIV detection
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All HIV infections detected during the study including prior to, during and after study treatment
Arm/Group Title TDF/FTC Placebo
Hide Arm/Group Description:
Daily oral emtricitabine/tenofovir disoproxil fumarate
Daily oral placebo
Overall Number of Participants Analyzed 54 93
Mean (Standard Error)
Unit of Measure: log RNA copies per ml
5.2  (0.11) 5.1  (0.08)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TDF/FTC, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.56
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.08
Confidence Interval (2-Sided) 95%
-.18 to 0.33
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Among HIV Infected Participants Drug Resistance
Hide Description Genotypic resistance by clinical assays among the seroconverters from baseline to the end of the study treatment period
Time Frame at the time of HIV acquisition
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
There were 2 TDF/FTC seroconversions at enrollment and 48 during follow-up. There were 8 Placebo seroconversions at enrollment and 83 during follow-up.
Arm/Group Title TDF/FTC Placebo
Hide Arm/Group Description:

Daily oral emtricitabine/tenofovir disoproxil fumarate

Emtricitabine/tenofovir disoproxil fumarate: Fixed-dose coformulation of 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate

Daily oral placebo

Placebo: Placebo for emtricitabine/tenofovir disoproxil fumarate

Overall Number of Participants Analyzed 50 91
Measure Type: Count of Participants
Unit of Measure: Participants
Infected at Enrollment (prior to randomization) Number Analyzed 2 participants 8 participants
2
 100.0%
1
  12.5%
Infected after Randomization Number Analyzed 48 participants 83 participants
0
   0.0%
0
   0.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TDF/FTC, Placebo
Comments Null hypothesis is the proportion of mutations is identical.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.00
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.00
Estimation Comments [Not Specified]
13.Secondary Outcome
Title CD4 Count Among HIV Infected Participants
Hide Description CD4 cell count for HIV infected participants during the trial
Time Frame at the time infection was detected
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
HIV infected participants during the trial including those HIV+ at baseline
Arm/Group Title TDF/FTC Placebo
Hide Arm/Group Description:
Daily oral emtricitabine/tenofovir disoproxil fumarate
Daily oral placebo
Overall Number of Participants Analyzed 51 87
Mean (95% Confidence Interval)
Unit of Measure: cells per cubic mm
495
(470 to 520)
502
(483 to 521)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TDF/FTC, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.32
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -7
Confidence Interval (2-Sided) 95%
-69 to 54
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Proportion of Missed Doses by Pill Count
Hide Description Estimated proportion of missed doses by pill count (assuming pills taken in unreturned bottles)
Time Frame At 24 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Those who bottles returned at the week 24 visit.
Arm/Group Title TDF/FTC Placebo
Hide Arm/Group Description:

Daily oral emtricitabine/tenofovir disoproxil fumarate

Emtricitabine/tenofovir disoproxil fumarate: Fixed-dose coformulation of 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate

Daily oral placebo

Placebo: Placebo for emtricitabine/tenofovir disoproxil fumarate

Overall Number of Participants Analyzed 983 999
Mean (95% Confidence Interval)
Unit of Measure: proportion of pills not returned
0.92
(0.91 to 0.93)
0.93
(0.92 to 0.94)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TDF/FTC, Placebo
Comments Null hypothesis is equal proportion of pills returned
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.53
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.005
Confidence Interval (2-Sided) 95%
-0.02 to 0.01
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Percentage of Missed Doses by Estimate During CASI Interview
Hide Description Percentage of missed doses by estimate during computer assisted structured interview
Time Frame Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who answered the adherence question with an estimated adherence on the week 24 computer assisted structured interview
Arm/Group Title TDF/FTC Placebo
Hide Arm/Group Description:
Daily oral emtricitabine/tenofovir disoproxil fumarate
Daily oral placebo
Overall Number of Participants Analyzed 884 902
Mean (Standard Error)
Unit of Measure: percentage of doses taken
91.0  (0.5) 91.2  (0.50)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TDF/FTC, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.70
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.25
Confidence Interval (2-Sided) 95%
-1.1 to 1.6
Estimation Comments [Not Specified]
16.Secondary Outcome
Title Number of Condomless Sexual Partners With HIV Positive or Unknown Status
Hide Description Participants self-report of the number of sexual partners with HIV positive or unknown status in the previous 12 weeks with whom they had condomless anal sex
Time Frame At 24 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants interviewed about sexual practices at week 24
Arm/Group Title TDF/FTC Placebo
Hide Arm/Group Description:
Daily oral emtricitabine/tenofovir disoproxil fumarate
Daily oral placebo
Overall Number of Participants Analyzed 1091 1114
Median (Inter-Quartile Range)
Unit of Measure: count
0
(0 to 0)
0
(0 to 0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TDF/FTC, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.99
Comments Not adjusted for multiple comparisons and the a priori threshold for statistical significance was p < 0.05
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0
Estimation Comments [Not Specified]
17.Secondary Outcome
Title Total Number of Sexual Partners
Hide Description Self-reported total number of sexual partners in the previous 12 weeks.
Time Frame 24 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants interviewed about sexual practices at week 24
Arm/Group Title TDF/FTC Placebo
Hide Arm/Group Description:
Daily oral emtricitabine/tenofovir disoproxil fumarate
Daily oral placebo
Overall Number of Participants Analyzed 1091 1114
Median (Inter-Quartile Range)
Unit of Measure: Count
3
(1 to 6)
3
(1 to 7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TDF/FTC, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.76
Comments Not adjusted for multiple comparisons, a priori threshold for statistical significance, p < 0.05
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 0
Confidence Interval (2-Sided) 95%
-.42 to .42
Estimation Comments [Not Specified]
18.Secondary Outcome
Title Condomless Receptive Anal Intercourse in the Previous 12 Weeks With Any Partners Regardless of Status.
Hide Description Self-reported condomless receptive anal intercourse in the previous 12 weeks with any partners regardless of status.
Time Frame At 24 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants interviewed about sexual practices at week 24
Arm/Group Title TDF/FTC Placebo
Hide Arm/Group Description:

Daily oral emtricitabine/tenofovir disoproxil fumarate

Emtricitabine/tenofovir disoproxil fumarate: Fixed-dose coformulation of 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate

Daily oral placebo

Placebo: Placebo for emtricitabine/tenofovir disoproxil fumarate

Overall Number of Participants Analyzed 1091 1114
Measure Type: Count of Participants
Unit of Measure: Participants
332
  30.4%
348
  31.2%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TDF/FTC, Placebo
Comments Null is no difference between arms
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.68
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -0.008
Confidence Interval (2-Sided) 95%
-0.047 to 0.030
Estimation Comments [Not Specified]
19.Secondary Outcome
Title Incidence of Confirmed Syphilis During Follow-Up
Hide Description Number of participants who have at least 1 confirmed syphilis infection during the study
Time Frame All Follow-Up median of 1.2 years of follow-up
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants without active syphilis at baseline with a follow-up syphilis test.
Arm/Group Title TDF/FTC Placebo
Hide Arm/Group Description:

Daily oral emtricitabine/tenofovir disoproxil fumarate

Emtricitabine/tenofovir disoproxil fumarate: Fixed-dose coformulation of 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate

Daily oral placebo

Placebo: Placebo for emtricitabine/tenofovir disoproxil fumarate

Overall Number of Participants Analyzed 1155 1171
Measure Type: Count of Participants
Unit of Measure: Participants
147
  12.7%
132
  11.3%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TDF/FTC, Placebo
Comments Null hypothesis of no difference between the arms
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.30
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.13
Confidence Interval (2-Sided) 95%
0.89 to 1.43
Estimation Comments [Not Specified]
20.Secondary Outcome
Title Incidence of HSV-2 During the Follow-up Period
Hide Description Incidence of HSV-2 during the follow-up period among those HIV-2 negative at baseline
Time Frame Total study follow-up, a median of 1.2 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All HSV-2 negative participants with a follow-up HSV-2 test.
Arm/Group Title TDF/FTC Placebo
Hide Arm/Group Description:
Daily oral emtricitabine/tenofovir disoproxil fumarate
Daily oral placebo
Overall Number of Participants Analyzed 671 676
Measure Type: Count of Participants
Unit of Measure: Participants
65
   9.7%
60
   8.9%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TDF/FTC, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.41
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.2
Confidence Interval (2-Sided) 95%
0.8 to 1.7
Estimation Comments [Not Specified]
21.Secondary Outcome
Title Diagnosis of Gonorrhea During the Follow-up Period
Hide Description Diagnosis of gonorrhea during the follow-up period by PCR
Time Frame All of follow-up period, median of 1.2 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants with at least one follow-up test for gonorrhea
Arm/Group Title TDF/FTC Placebo
Hide Arm/Group Description:
Daily oral emtricitabine/tenofovir disoproxil fumarate
Daily oral placebo
Overall Number of Participants Analyzed 1226 1229
Measure Type: Count of Participants
Unit of Measure: Participants
18
   1.5%
30
   2.4%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TDF/FTC, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.09
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.61
Confidence Interval (2-Sided) 95%
0.34 to 1.09
Estimation Comments [Not Specified]
Time Frame Monthly follow-up with quarterly lab assessments though a median of 1.2 years of follow-up
Adverse Event Reporting Description Adverse events graded by the NIH Division of AIDS grading tables, version 1.0
 
Arm/Group Title TDF/FTC Placebo
Hide Arm/Group Description

Daily oral emtricitabine/tenofovir disoproxil fumarate

Emtricitabine/tenofovir disoproxil fumarate: Fixed-dose coformulation of 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate

Daily oral placebo

Placebo: Placebo for emtricitabine/tenofovir disoproxil fumarate

All-Cause Mortality
TDF/FTC Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
TDF/FTC Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   92/1226 (7.50%)      94/1230 (7.64%)    
Blood and lymphatic system disorders     
CREATININE INCREASE  1  9/1226 (0.73%)  9 7/1230 (0.57%)  7
ALT INCREASE  1  1/1226 (0.08%)  1 4/1230 (0.33%)  4
AST  1  4/1226 (0.33%)  4 5/1230 (0.41%)  5
General disorders     
OTHER EVENTS  1 [1]  28/1226 (2.28%)  28 29/1230 (2.36%)  29
Hepatobiliary disorders     
APPENDICITIS  1  3/1226 (0.24%)  3 3/1230 (0.24%)  3
Musculoskeletal and connective tissue disorders     
Bone Fracture  1  8/1226 (0.65%)  8 9/1230 (0.73%)  9
Psychiatric disorders     
SUICIDE ATTEMPT  1  17/1226 (1.39%)  17 14/1230 (1.14%)  14
SUICIDAL IDEATION  1  5/1226 (0.41%)  5 6/1230 (0.49%)  6
DEPRESSION  1  7/1226 (0.57%)  7 11/1230 (0.89%)  11
SUICIDAL DEPRESSION  1  5/1226 (0.41%)  5 6/1230 (0.49%)  6
MAJOR DEPRESSION  1  5/1226 (0.41%)  5 0/1230 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (10.0)
[1]
EVENTS AFFECTING LESS THAN A TOTAL OF 5 PARTICIPANTS
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
TDF/FTC Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   906/1226 (73.90%)      937/1230 (76.18%)    
Gastrointestinal disorders     
PARASITIC INFECTION INTESTINAL  1  231/1226 (18.84%)  231 216/1230 (17.56%)  216
DIARRHOEA  1  109/1226 (8.89%)  109 123/1230 (10.00%)  123
Infections and infestations     
SYPHILIS  1  82/1226 (6.69%)  82 71/1230 (5.77%)  71
UPPER RESPIRATORY TRACT INFECTION  1  73/1226 (5.95%)  73 76/1230 (6.18%)  76
SECONDARY SYPHILIS  1  81/1226 (6.61%)  81 64/1230 (5.20%)  64
BLOOD AMYLASE INCREASED  1  62/1226 (5.06%)  62 57/1230 (4.63%)  57
Investigations     
ALANINE AMINOTRANSFERASE INCREASED  1  151/1226 (12.32%)  151 155/1230 (12.60%)  155
BILIRUBIN INCREASE  1  127/1226 (10.36%)  127 132/1230 (10.73%)  132
BLOOD GLUCOSE INCREASED  1  109/1226 (8.89%)  109 123/1230 (10.00%)  123
BLOOD PHOSPHORUS DECREASED  1  122/1226 (9.95%)  122 100/1230 (8.13%)  100
ASPARTATE AMINOTRANSFERASE INCREASED  1  76/1226 (6.20%)  76 93/1230 (7.56%)  93
Musculoskeletal and connective tissue disorders     
BACK PAIN  1  84/1226 (6.85%)  84 87/1230 (7.07%)  87
Nervous system disorders     
HEADACHE  1  102/1226 (8.32%)  102 107/1230 (8.70%)  107
DEPRESSION  1  81/1226 (6.61%)  81 84/1230 (6.83%)  84
Renal and urinary disorders     
URETHRITIS  1  84/1226 (6.85%)  84 102/1230 (8.29%)  102
Respiratory, thoracic and mediastinal disorders     
PHARYNGITIS  1  248/1226 (20.23%)  248 282/1230 (22.93%)  282
NASOPHARYNGITIS  1  98/1226 (7.99%)  98 92/1230 (7.48%)  92
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (10.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: David Glidden
Organization: University of California, San Francisco
Phone: 415-514-8009
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00458393     History of Changes
Obsolete Identifiers: NCT00350324
Other Study ID Numbers: CO-US-104-0288
10445 ( Registry Identifier: DAIDS ES )
1U01AI064002 ( U.S. NIH Grant/Contract )
iPrEx ( Other Identifier: Study team )
First Submitted: April 6, 2007
First Posted: April 10, 2007
Results First Submitted: December 27, 2016
Results First Posted: January 24, 2018
Last Update Posted: January 24, 2018