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Safety and Effectiveness of TFV 1% Gel, TDF Tablets, and FTC/TDF Tablets in Preventing HIV in Women

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ClinicalTrials.gov Identifier: NCT00705679
Recruitment Status : Completed
First Posted : June 26, 2008
Results First Posted : February 10, 2016
Last Update Posted : March 14, 2016
Sponsor:
Collaborator:
Microbicide Trials Network
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: None (Open Label);   Primary Purpose: Prevention
Condition HIV Infections
Interventions Drug: Emtricitabine/tenofovir disoproxil fumarate
Drug: Emtricitabine/tenofovir disoproxil fumarate placebo
Drug: Tenofovir disoproxil fumarate
Drug: Tenofovir disoproxil fumarate placebo
Drug: Tenofovir 1% vaginal gel
Drug: Tenofovir placebo
Enrollment 5029
Recruitment Details Women were recruited from September 2009 through June 2011 from 15 sites in South Africa, Uganda, and Zimbabwe.
Pre-assignment Details 12,320 women were assessed for eligibility and 7,291 were excluded for various reasons, including 2,308 women who were HIV-positive. 5,029 women were randomized.
Arm/Group Title Oral TDF Oral TDF-FTC Oral Placebo TFV Gel Gel Placebo
Hide Arm/Group Description

TDF 300 mg tablet taken orally once daily and one FTC/TDF placebo tablet taken orally once daily for 12 to 36 months

Emtricitabine/tenofovir disoproxil fumarate placebo: placebo tablet

Tenofovir disoproxil fumarate: 300 mg tablet

TDF placebo tablet taken orally once daily and one FTC 200 mg/TDF 300 mg tablet taken orally once daily for 12 to 36 months

Emtricitabine/tenofovir disoproxil fumarate: 200 mg/300 mg tablet

Tenofovir disoproxil fumarate placebo: placebo tablet

TDF placebo tablet taken orally once daily and one FTC/TDF placebo tablet taken orally once daily for 12 to 36 months

Emtricitabine/tenofovir disoproxil fumarate placebo: placebo tablet

Tenofovir disoproxil fumarate placebo: placebo tablet

Application of tenofovir 1% vaginal gel once daily

Tenofovir 1% vaginal gel: 1 gm/100 ml of 1% gel

Application of tenofovir placebo gel once daily

Tenofovir placebo: placebo gel

Period Title: Overall Study
Started 1007 1003 1009 1007 1003
Completed 942 864 894 927 934
Not Completed 65 139 115 80 69
Reason Not Completed
Adverse Event             1             1             0             0             0
Death             0             0             3             2             1
Lost to Follow-up             32             60             44             30             35
Physician Decision             0             1             0             1             0
Withdrawal by Subject             32             77             68             47             33
Arm/Group Title Oral TDF Oral TDF-FTC Oral Placebo TFV Gel Gel Placebo Total
Hide Arm/Group Description

TDF 300 mg tablet taken orally once daily and one FTC/TDF placebo tablet taken orally once daily for 12 to 36 months

Emtricitabine/tenofovir disoproxil fumarate placebo: placebo tablet

Tenofovir disoproxil fumarate: 300 mg tablet

TDF placebo tablet taken orally once daily and one FTC 200 mg/TDF 300 mg tablet taken orally once daily for 12 to 36 months

Emtricitabine/tenofovir disoproxil fumarate: 200 mg/300 mg tablet

Tenofovir disoproxil fumarate placebo: placebo tablet

TDF placebo tablet taken orally once daily and one FTC/TDF placebo tablet taken orally once daily for 12 to 36 months

Emtricitabine/tenofovir disoproxil fumarate placebo: placebo tablet

Tenofovir disoproxil fumarate placebo: placebo tablet

Application of tenofovir 1% vaginal gel once daily

Tenofovir 1% vaginal gel: 1 gm/100 ml of 1% gel

Application of tenofovir placebo gel once daily

Tenofovir placebo: placebo gel

Total of all reporting groups
Overall Number of Baseline Participants 1007 1003 1009 1007 1003 5029
Hide Baseline Analysis Population Description
Includes all participants enrolled and randomized to a study arm
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 1007 participants 1003 participants 1009 participants 1007 participants 1003 participants 5029 participants
25.5  (5.1) 25.2  (5.2) 25.3  (5.2) 25.3  (5.2) 25.3  (5.1) 25.3  (5.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1007 participants 1003 participants 1009 participants 1007 participants 1003 participants 5029 participants
Female
1007
 100.0%
1003
 100.0%
1009
 100.0%
1007
 100.0%
1003
 100.0%
5029
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 1007 participants 1003 participants 1009 participants 1007 participants 1003 participants 5029 participants
Chichewa 4 10 7 7 2 30
Lombwe 0 0 0 0 1 1
Yao 1 0 0 0 1 2
Tumbuka 0 1 1 0 1 3
Other African tribe 76 75 83 92 84 410
White 0 0 0 0 0 0
Zulu 601 587 595 585 571 2939
Xhosa 85 75 74 72 92 398
Indian 21 28 22 22 22 115
Colored 0 3 3 4 1 11
Black 64 64 65 65 64 322
Bemba 0 0 0 0 0 0
Chewa 1 1 0 0 0 2
Tonga 0 0 0 0 0 0
Lozi 0 0 0 0 0 0
Shona 123 108 111 111 117 570
Ndebele 14 27 18 25 22 106
Other 17 24 30 24 25 120
[1]
Measure Description: Response to the question: What is your ethnic group or tribe?
Region of Enrollment   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 1007 participants 1003 participants 1009 participants 1007 participants 1003 participants 5029 participants
South Africa 816 812 815 818 816 4077
Uganda 64 64 65 65 64 322
Zimbabwe 127 127 129 124 123 630
[1]
Measure Description: Country at time of enrollment
Some secondary school education or higher   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 1007 participants 1003 participants 1009 participants 1007 participants 1003 participants 5029 participants
Some secondary school education or higher 924 929 926 920 923 4622
Complete primary school education or lower 82 74 83 85 79 403
Missing 1 0 0 2 1 4
[1]
Measure Description: Response to question: What is your highest level of education?
Earns own income   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 1007 participants 1003 participants 1009 participants 1007 participants 1003 participants 5029 participants
Yes 569 569 586 587 570 2881
No 438 434 423 420 432 2147
Missing 0 0 0 0 1 1
[1]
Measure Description: Response to question: Do you earn an income of your own?
Live births   [1] 
Mean (Standard Deviation)
Unit of measure:  Children
Number Analyzed 1007 participants 1003 participants 1009 participants 1007 participants 1003 participants 5029 participants
1.6  (1.1) 1.5  (1.1) 1.5  (1.2) 1.5  (1.1) 1.5  (1.2) 1.5  (1.1)
[1]
Measure Description: Response to question: How many children have you given birth to who were alive at birth?
Currently married   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 1007 participants 1003 participants 1009 participants 1007 participants 1003 participants 5029 participants
Yes 207 209 211 210 215 1052
No 800 794 798 797 788 3977
[1]
Measure Description: Response to question: Are you currently married?
At least 2 male sex partners in the past 3 months   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 1007 participants 1003 participants 1009 participants 1007 participants 1003 participants 5029 participants
Yes 236 208 244 217 199 1104
No 761 782 754 779 793 3869
No response 10 13 11 11 11 56
[1]
Measure Description: Includes primary partner and at least 1 other male partner with which the participant has had vaginal sex in the past 3 months
Episodes of vaginal intercourse in the past 7 days  
Mean (Standard Deviation)
Unit of measure:  Episodes
Number Analyzed 1007 participants 1003 participants 1009 participants 1007 participants 1003 participants 5029 participants
2.5  (2.8) 2.5  (3.4) 2.5  (2.6) 2.6  (3.6) 2.6  (2.9) 2.5  (3.1)
Condom use during last vaginal intercourse  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 1007 participants 1003 participants 1009 participants 1007 participants 1003 participants 5029 participants
Yes 763 760 742 768 733 3766
No 242 239 263 239 268 1251
Missing 2 4 4 0 2 12
Anal sex in the previous 3 months   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 1007 participants 1003 participants 1009 participants 1007 participants 1003 participants 5029 participants
Yes 164 175 174 179 176 868
No 827 812 823 814 810 4086
Missing 16 16 12 14 17 75
[1]
Measure Description: A response of 1 or more to the question: In the past 3 months how many times have you had anal sex?
Injectable contraception use   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 1007 participants 1003 participants 1009 participants 1007 participants 1003 participants 5029 participants
Yes 709 723 700 707 726 3565
No 298 280 309 300 277 1464
[1]
Measure Description: Response to question: What method(s) of contraception/family planning is the participant currently using? (Participant could indicate more than one method.)
Oral pills contraception   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 1007 participants 1003 participants 1009 participants 1007 participants 1003 participants 5029 participants
Yes 226 223 238 238 215 1140
No 781 780 771 769 788 3889
[1]
Measure Description: Response to question: What method(s) of contraception/family planning is the participant currently using? (Participant could indicate more than one method.)
Infection by Chlamydia trachomatis   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 1007 participants 1003 participants 1009 participants 1007 participants 1003 participants 5029 participants
Yes 122 117 127 116 129 611
No 884 886 882 891 874 4417
Missing 1 0 0 0 0 1
[1]
Measure Description: Testing was performed with the use of a strand-displacement amplification assay
Infection by Neisseria gonorrhoeae   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 1007 participants 1003 participants 1009 participants 1007 participants 1003 participants 5029 participants
Yes 42 27 34 24 36 163
No 964 976 975 983 967 4865
Missing 1 0 0 0 0 1
[1]
Measure Description: Testing was performed with the use of a strand-displacement amplification assay
Infection by Trichomonas vaginalis   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 1007 participants 1003 participants 1009 participants 1007 participants 1003 participants 5029 participants
Yes 68 54 66 62 51 301
No 939 948 943 943 949 4722
Missing 0 1 0 2 3 6
[1]
Measure Description: Testing was performed with the use of the OSOM Trichomonas Rapid Test
Syphilis infection   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 1007 participants 1003 participants 1009 participants 1007 participants 1003 participants 5029 participants
Yes 12 15 16 14 11 68
No 994 988 993 993 992 4960
Missing 1 0 0 0 0 1
[1]
Measure Description: Testing was performed with the use of a rapid plasma reagin screening test followed by a confirmatory microhemagglutinin assay
HSV-2 infection   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 1007 participants 1003 participants 1009 participants 1007 participants 1003 participants 5029 participants
Yes 482 449 455 438 465 2289
No 520 548 551 566 531 2716
Missing 5 6 3 3 7 24
[1]
Measure Description: HSV-2 seropositivity was determined with the use of the HerpeSelect 2 enzyme immunoassay at the time of enrollment; an index value of 3.5 or greater was considered to be a positive result.
Bacterial vaginosis infection   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 1007 participants 1003 participants 1009 participants 1007 participants 1003 participants 5029 participants
Yes 422 410 401 397 393 2023
No 578 592 607 606 604 2987
Missing 7 1 1 4 6 19
[1]
Measure Description: Bacterial vaginosis was determined by the Nugent score on Gram's staining of vaginal fluid (Nugent score 7-10).
1.Primary Outcome
Title Person-years of Follow-up of Tenofovir 1% Gel and Vaginal Placebo Gel Arms
Hide Description Participants were followed for up to 30 months. Person-years measures the amount of time for each participant, in years, from the date of enrollment to the date of the first HIV-positive test result if HIV-infected during follow-up or to the date of the last HIV-negative test result on follow-up if not HIV-infected during follow-up.
Time Frame For up to 30 months of follow-up
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants randomized except for those with no follow-up HIV testing or those determined to be HIV-positive at the time of randomization by PCR testing of plasma samples stored at the enrollment visit.
Arm/Group Title TFV Gel Placebo Gel
Hide Arm/Group Description:
Application of tenofovir 1% vaginal gel once daily Tenofovir 1% vaginal gel: 1 gm/100 ml of 1% gel
Application of placebo gel once daily Tenofovir placebo gel: placebo gel
Overall Number of Participants Analyzed 996 996
Measure Type: Number
Unit of Measure: person-years
1024 1030
2.Primary Outcome
Title Number of HIV-1 Infections of Tenofovir 1% Gel and Vaginal Placebo Gel Arms
Hide Description Participants were followed for up to 30 months. Participants were tested monthly for HIV-1 and positive rapid test results were confirmed by means of an enzyme-linked immunosorbent assay (EIA) and subsequent Western blotting (WB).
Time Frame For up to 30 months of follow-up
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants randomized except for those with no follow-up HIV testing or those determined to be HIV-positive at the time of randomization by PCR testing of plasma samples stored at the enrollment visit.
Arm/Group Title TFV Gel Placebo Gel
Hide Arm/Group Description:
Application of tenofovir 1% vaginal gel once daily Tenofovir 1% vaginal gel: 1 gm/100 ml of 1% gel
Application of placebo gel once daily Tenofovir placebo gel: placebo gel
Overall Number of Participants Analyzed 996 996
Measure Type: Number
Unit of Measure: participants
61 70
3.Primary Outcome
Title Incidence Rate of HIV-1 Infections of Tenofovir 1% Gel and Vaginal Placebo Gel Arms
Hide Description This is the number of HIV-1 infections divided by the amount of person-years of follow-up time to HIV-1 infection status, multiplied by 100 (per 100 person-years).
Time Frame For up to 30 months of follow-up
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants randomized except for those with no follow-up HIV testing or those determined to be HIV-positive at the time of randomization by PCR testing of plasma samples stored at the enrollment visit.
Arm/Group Title TFV Gel Placebo Gel
Hide Arm/Group Description:
Application of tenofovir 1% vaginal gel once daily Tenofovir 1% vaginal gel: 1 gm/100 ml of 1% gel
Application of placebo gel once daily Tenofovir placebo gel: placebo gel
Overall Number of Participants Analyzed 996 996
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: cases per 100 person-years
6.0
(4.6 to 7.6)
6.8
(5.3 to 8.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TFV Gel, Placebo Gel
Comments The null hypothesis is that the active product will be no more than 25% effective. The trial was designed so that 94 events per pairwise comparison are needed to detect 55% effectiveness while ruling out a lower effectiveness of 25% with 90% power and a false-positive error rate of 0.0025.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.37
Comments The two-sided test a priori threshold for statistical significance is 0.05 against an alternative of 0% effectiveness for estimated effectiveness levels between 33.3% and 50.0%.
Method Regression, Cox
Comments The Cox proportional-hazards model was stratified by site.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.85
Confidence Interval (2-Sided) 95%
0.61 to 1.21
Estimation Comments A ratio less than 1 indicates a lower rate of HIV infection in the active arm compared to the placebo arm. A ratio more than 1 indicates a higher rate of HIV infection in the active arm compared to the placebo arm.
4.Primary Outcome
Title Person-years of Follow-up of Oral TDF and Oral Placebo Arms
Hide Description Participants were followed for up to 30 months. Person-years measures the amount of time for each participant, in years, from the date of enrollment to the date of the first HIV-positive test result if HIV-infected during follow-up or to the date of the last HIV-negative test result on follow-up if not HIV-infected during follow-up. Note that the data for both of these arms were censored on the date when sites were asked to discontinue treatment in the oral TDF group.
Time Frame For up to 30 months of follow-up
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants randomized except for those with no follow-up HIV testing or those determined to be HIV-positive at the time of randomization by PCR testing of plasma samples stored at the enrollment visit.
Arm/Group Title Oral TDF Oral Placebo
Hide Arm/Group Description:
TDF 300 mg tablet taken orally once daily and one FTC/TDF placebo tablet taken orally once daily for 12 to 36 months Emtricitabine/tenofovir disoproxil fumarate placebo: placebo tablet Tenofovir disoproxil fumarate: 300 mg tablet
TDF placebo tablet taken orally once daily and one FTC/TDF placebo tablet taken orally once daily for 12 to 36 months Emtricitabine/tenofovir disoproxil fumarate placebo: placebo tablet Tenofovir disoproxil fumarate placebo: placebo tablet
Overall Number of Participants Analyzed 993 999
Measure Type: Number
Unit of Measure: person-years
823 838
5.Primary Outcome
Title Number of HIV-1 Infections of Oral TDF and Oral Placebo Arms
Hide Description Participants were followed for up to 30 months. Participants were tested monthly for HIV-1 and positive rapid test results were confirmed by means of an enzyme-linked immunosorbent assay (EIA) and subsequent Western blotting (WB).
Time Frame For up to 30 months of follow-up
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants randomized except for those with no follow-up HIV testing or those determined to be HIV-positive at the time of randomization by PCR testing of plasma samples stored at the enrollment visit.
Arm/Group Title Oral TDF Oral Placebo
Hide Arm/Group Description:
TDF 300 mg tablet taken orally once daily and one FTC/TDF placebo tablet taken orally once daily for 12 to 36 months Emtricitabine/tenofovir disoproxil fumarate placebo: placebo tablet Tenofovir disoproxil fumarate: 300 mg tablet
TDF placebo tablet taken orally once daily and one FTC/TDF placebo tablet taken orally once daily for 12 to 36 months Emtricitabine/tenofovir disoproxil fumarate placebo: placebo tablet Tenofovir disoproxil fumarate placebo: placebo tablet
Overall Number of Participants Analyzed 993 999
Measure Type: Number
Unit of Measure: participants
52 35
6.Primary Outcome
Title Incidence Rate of HIV-1 Infections of Oral TDF and Oral Placebo Arms
Hide Description This is the number of HIV-1 infections divided by the amount of person-years of follow-up time to HIV-1 infection status, multiplied by 100 (per 100 person-years).
Time Frame For up to 30 months of follow-up
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants randomized except for those with no follow-up HIV testing or those determined to be HIV-positive at the time of randomization by PCR testing of plasma samples stored at the enrollment visit.
Arm/Group Title Oral TDF Oral Placebo
Hide Arm/Group Description:
TDF 300 mg tablet taken orally once daily and one FTC/TDF placebo tablet taken orally once daily for 12 to 36 months Emtricitabine/tenofovir disoproxil fumarate placebo: placebo tablet Tenofovir disoproxil fumarate: 300 mg tablet
TDF placebo tablet taken orally once daily and one FTC/TDF placebo tablet taken orally once daily for 12 to 36 months Emtricitabine/tenofovir disoproxil fumarate placebo: placebo tablet Tenofovir disoproxil fumarate placebo: placebo tablet
Overall Number of Participants Analyzed 993 999
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: cases per 100 person-years
6.3
(4.7 to 8.3)
4.2
(2.9 to 5.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral TDF, Oral Placebo
Comments The null hypothesis is that the active product will be no more than 25% effective. The trial was designed so that 94 events per pairwise comparison are needed to detect 55% effectiveness while ruling out a lower effectiveness of 25% with 90% power and a false-positive error rate of 0.0025.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.07
Comments The two-sided test a priori threshold for statistical significance is 0.05 against an alternative of 0% effectiveness for estimated effectiveness levels between 33.3% and 50.0%.
Method Regression, Cox
Comments The Cox proportional-hazards model was stratified by site.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.49
Confidence Interval (2-Sided) 95%
0.97 to 2.29
Estimation Comments A ratio less than 1 indicates a lower rate of HIV infection in the active arm compared to the placebo arm. A ratio more than 1 indicates a higher rate of HIV infection in the active arm compared to the placebo arm.
7.Primary Outcome
Title Person-years of Follow-up of Oral TDF-FTC and Oral Placebo Arms
Hide Description Participants were followed for up to 30 months. Person-years measures the amount of time for each participant, in years, from the date of enrollment to the date of the first HIV-positive test result if HIV-infected during follow-up or to the date of the last HIV-negative test result on follow-up if not HIV-infected during follow-up.
Time Frame For up to 30 months of follow-up
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants randomized except for those with no follow-up HIV testing or those determined to be HIV-positive at the time of randomization by PCR testing of plasma samples stored at the enrollment visit.
Arm/Group Title Oral TDF-FTC Oral Placebo
Hide Arm/Group Description:
TDF placebo tablet taken orally once daily and one FTC 200 mg/TDF 300 mg tablet taken orally once daily for 12 to 36 months Emtricitabine/tenofovir disoproxil fumarate: 200 mg/300 mg tablet Tenofovir disoproxil fumarate placebo: placebo tablet
TDF placebo tablet taken orally once daily and one FTC/TDF placebo tablet taken orally once daily for 12 to 36 months Emtricitabine/tenofovir disoproxil fumarate placebo: placebo tablet Tenofovir disoproxil fumarate placebo: placebo tablet
Overall Number of Participants Analyzed 985 999
Measure Type: Number
Unit of Measure: person-years
1284 1308
8.Primary Outcome
Title Number of HIV-1 Infections of Oral TDF-FTC and Oral Placebo Arms
Hide Description Participants were followed for up to 30 months. Participants were tested monthly for HIV-1 and positive rapid test results were confirmed by means of an enzyme-linked immunosorbent assay (EIA) and subsequent Western blotting (WB).
Time Frame For up to 30 months of follow-up
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants randomized except for those with no follow-up HIV testing or those determined to be HIV-positive at the time of randomization by PCR testing of plasma samples stored at the enrollment visit.
Arm/Group Title Oral TDF-FTC Oral Placebo
Hide Arm/Group Description:
TDF placebo tablet taken orally once daily and one FTC 200 mg/TDF 300 mg tablet taken orally once daily for 12 to 36 months Emtricitabine/tenofovir disoproxil fumarate: 200 mg/300 mg tablet Tenofovir disoproxil fumarate placebo: placebo tablet
TDF placebo tablet taken orally once daily and one FTC/TDF placebo tablet taken orally once daily for 12 to 36 months Emtricitabine/tenofovir disoproxil fumarate placebo: placebo tablet Tenofovir disoproxil fumarate placebo: placebo tablet
Overall Number of Participants Analyzed 985 999
Measure Type: Number
Unit of Measure: participants
61 60
9.Primary Outcome
Title Incidence Rate of HIV-1 Infections of Oral TDF-FTC and Oral Placebo Arms
Hide Description This is the number of HIV-1 infections divided by the amount of person-years of follow-up time to HIV-1 infection status, multiplied by 100 (per 100 person-years).
Time Frame For up to 30 months of follow-up
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants randomized except for those with no follow-up HIV testing or those determined to be HIV-positive at the time of randomization by PCR testing of plasma samples stored at the enrollment visit.
Arm/Group Title Oral TDF-FTC Oral Placebo
Hide Arm/Group Description:
TDF placebo tablet taken orally once daily and one FTC 200 mg/TDF 300 mg tablet taken orally once daily for 12 to 36 months Emtricitabine/tenofovir disoproxil fumarate: 200 mg/300 mg tablet Tenofovir disoproxil fumarate placebo: placebo tablet
TDF placebo tablet taken orally once daily and one FTC/TDF placebo tablet taken orally once daily for 12 to 36 months Emtricitabine/tenofovir disoproxil fumarate placebo: placebo tablet Tenofovir disoproxil fumarate placebo: placebo tablet
Overall Number of Participants Analyzed 985 999
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: cases per 100 person-years
4.7
(3.6 to 6.1)
4.6
(3.5 to 5.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral TDF-FTC, Oral Placebo
Comments The null hypothesis is that the active product will be no more than 25% effective. The trial was designed so that 94 events per pairwise comparison are needed to detect 55% effectiveness while ruling out a lower effectiveness of 25% with 90% power and a false-positive error rate of 0.0025.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.81
Comments The two-sided test a priori threshold for statistical significance is 0.05 against an alternative of 0% effectiveness for estimated effectiveness levels between 33.3% and 50.0%.
Method Regression, Cox
Comments The Cox proportional-hazards model was stratified by site.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.04
Confidence Interval (2-Sided) 95%
0.73 to 1.49
Estimation Comments A ratio less than 1 indicates a lower rate of HIV infection in the active arm compared to the placebo arm. A ratio more than 1 indicates a higher rate of HIV infection in the active arm compared to the placebo arm.
10.Primary Outcome
Title Extended Safety of Daily Tenofovir 1% Gel, Oral TDF, and Oral FTC/TDF in Women at Risk for Sexually Transmitted HIV Infection Based on Occurrence of Grade 2, 3, and 4 Adverse Events
Hide Description This measure describes the number of participants with elevated serum creatinine levels, the only safety outcome of concern where a significant difference was detected between an active arm and the corresponding placebo arm.
Time Frame Throughout study, up to 2.5 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants randomized (intention-to-treat).
Arm/Group Title Oral TDF Oral TDF-FTC Oral Placebo TFV Gel Gel Placebo
Hide Arm/Group Description:

TDF 300 mg tablet taken orally once daily and one FTC/TDF placebo tablet taken orally once daily for 12 to 36 months

Emtricitabine/tenofovir disoproxil fumarate placebo: placebo tablet

Tenofovir disoproxil fumarate: 300 mg tablet

TDF placebo tablet taken orally once daily and one FTC 200 mg/TDF 300 mg tablet taken orally once daily for 12 to 36 months

Emtricitabine/tenofovir disoproxil fumarate: 200 mg/300 mg tablet

Tenofovir disoproxil fumarate placebo: placebo tablet

TDF placebo tablet taken orally once daily and one FTC/TDF placebo tablet taken orally once daily for 12 to 36 months

Emtricitabine/tenofovir disoproxil fumarate placebo: placebo tablet

Tenofovir disoproxil fumarate placebo: placebo tablet

Application of tenofovir 1% vaginal gel once daily

Tenofovir 1% vaginal gel: 1 gm/100 ml of 1% gel

Application of tenofovir placebo gel once daily

Tenofovir placebo: placebo gel

Overall Number of Participants Analyzed 1007 1003 1009 1007 1003
Measure Type: Number
Unit of Measure: participants
4 13 2 9 3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral TDF-FTC, Oral Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method Fisher Exact
Comments Two-sided Fisher's Exact Test.
11.Secondary Outcome
Title Frequency of HIV-1 Drug Resistance in Women Who Acquire HIV-1 Infection While Using Study Product
Hide Description The primary resistance mutations for the study were pre-defined as K65R and K70E (which confer resistance to TDF), and M184I and M184V (which confer resistance to FTC), for their potential to cause a decrease in susceptibility to the study drug. K65R, K70E, and M184I were not detected in HIV-1 from any HIV-1 seroconverters while on study product. The number of HIV-1 seroconverters while on study with the M184V resistance mutation are reported for this outcome measure.
Time Frame Throughout study, up to 2.5 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Resistance testing was successfully completed on plasma from 301/312 HIV-1 seroconverters while on study product. 11 participants did not have a resistance result due to no stored plasma, insufficient copies of HIV-1 RNA for extraction, or PCR amplification failure.
Arm/Group Title Oral TDF Oral TDF-FTC Oral Placebo TFV Gel Gel Placebo
Hide Arm/Group Description:

TDF 300 mg tablet taken orally once daily and one FTC/TDF placebo tablet taken orally once daily for 12 to 36 months

Emtricitabine/tenofovir disoproxil fumarate placebo: placebo tablet

Tenofovir disoproxil fumarate: 300 mg tablet

TDF placebo tablet taken orally once daily and one FTC 200 mg/TDF 300 mg tablet taken orally once daily for 12 to 36 months

Emtricitabine/tenofovir disoproxil fumarate: 200 mg/300 mg tablet

Tenofovir disoproxil fumarate placebo: placebo tablet

TDF placebo tablet taken orally once daily and one FTC/TDF placebo tablet taken orally once daily for 12 to 36 months

Emtricitabine/tenofovir disoproxil fumarate placebo: placebo tablet

Tenofovir disoproxil fumarate placebo: placebo tablet

Application of tenofovir 1% vaginal gel once daily

Tenofovir 1% vaginal gel: 1 gm/100 ml of 1% gel

Application of tenofovir placebo gel once daily

Tenofovir placebo: placebo gel

Overall Number of Participants Analyzed 58 55 60 60 69
Measure Type: Number
Unit of Measure: participants
M184V mutation 0 1 0 0 0
No M184V mutation 58 54 60 60 68
Time Frame each participant followed on study up to 2 years, 6 months
Adverse Event Reporting Description Participants systematically reported any adverse experiences at monthly follow-up visits.
 
Arm/Group Title Oral TDF Oral TDF-FTC Oral Placebo TFV Gel Gel Placebo
Hide Arm/Group Description

TDF 300 mg tablet taken orally once daily and one FTC/TDF placebo tablet taken orally once daily for 12 to 36 months

Emtricitabine/tenofovir disoproxil fumarate placebo: placebo tablet

Tenofovir disoproxil fumarate: 300 mg tablet

TDF placebo tablet taken orally once daily and one FTC 200 mg/TDF 300 mg tablet taken orally once daily for 12 to 36 months

Emtricitabine/tenofovir disoproxil fumarate: 200 mg/300 mg tablet

Tenofovir disoproxil fumarate placebo: placebo tablet

TDF placebo tablet taken orally once daily and one FTC/TDF placebo tablet taken orally once daily for 12 to 36 months

Emtricitabine/tenofovir disoproxil fumarate placebo: placebo tablet

Tenofovir disoproxil fumarate placebo: placebo tablet

Application of tenofovir 1% vaginal gel once daily

Tenofovir 1% vaginal gel: 1 gm/100 ml of 1% gel

Application of tenofovir placebo gel once daily

Tenofovir placebo: placebo gel

All-Cause Mortality
Oral TDF Oral TDF-FTC Oral Placebo TFV Gel Gel Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Oral TDF Oral TDF-FTC Oral Placebo TFV Gel Gel Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   17/1007 (1.69%)   42/1003 (4.19%)   57/1009 (5.65%)   39/1007 (3.87%)   26/1003 (2.59%) 
Blood and lymphatic system disorders           
Lymph node pain  1  0/1007 (0.00%)  0/1003 (0.00%)  1/1009 (0.10%)  0/1007 (0.00%)  0/1003 (0.00%) 
Congenital, familial and genetic disorders           
Congenital anomaly in offspring  1  1/1007 (0.10%)  0/1003 (0.00%)  0/1009 (0.00%)  3/1007 (0.30%)  1/1003 (0.10%) 
Eye disorders           
Keratoconus  1  0/1007 (0.00%)  1/1003 (0.10%)  0/1009 (0.00%)  0/1007 (0.00%)  0/1003 (0.00%) 
Retinal detachment  1  0/1007 (0.00%)  1/1003 (0.10%)  0/1009 (0.00%)  0/1007 (0.00%)  0/1003 (0.00%) 
Gastrointestinal disorders           
Abdominal pain  1  0/1007 (0.00%)  0/1003 (0.00%)  1/1009 (0.10%)  0/1007 (0.00%)  1/1003 (0.10%) 
Abdominal pain upper  1  0/1007 (0.00%)  1/1003 (0.10%)  0/1009 (0.00%)  1/1007 (0.10%)  0/1003 (0.00%) 
Diarrhoea  1  0/1007 (0.00%)  0/1003 (0.00%)  0/1009 (0.00%)  1/1007 (0.10%)  0/1003 (0.00%) 
Food poisoning  1  0/1007 (0.00%)  0/1003 (0.00%)  0/1009 (0.00%)  0/1007 (0.00%)  1/1003 (0.10%) 
Gastric ulcer  1  0/1007 (0.00%)  0/1003 (0.00%)  1/1009 (0.10%)  0/1007 (0.00%)  1/1003 (0.10%) 
Gastritis  1  0/1007 (0.00%)  0/1003 (0.00%)  1/1009 (0.10%)  0/1007 (0.00%)  1/1003 (0.10%) 
Umbilical hernia  1  0/1007 (0.00%)  0/1003 (0.00%)  1/1009 (0.10%)  0/1007 (0.00%)  0/1003 (0.00%) 
Vomiting  1  0/1007 (0.00%)  0/1003 (0.00%)  1/1009 (0.10%)  0/1007 (0.00%)  0/1003 (0.00%) 
General disorders           
Death  1  0/1007 (0.00%)  0/1003 (0.00%)  0/1009 (0.00%)  1/1007 (0.10%)  0/1003 (0.00%) 
Suprapubic pain  1  0/1007 (0.00%)  0/1003 (0.00%)  0/1009 (0.00%)  1/1007 (0.10%)  0/1003 (0.00%) 
Hepatobiliary disorders           
Cholecystitis  1  0/1007 (0.00%)  0/1003 (0.00%)  1/1009 (0.10%)  1/1007 (0.10%)  0/1003 (0.00%) 
Drug-induced liver injury  1  0/1007 (0.00%)  0/1003 (0.00%)  1/1009 (0.10%)  0/1007 (0.00%)  0/1003 (0.00%) 
Infections and infestations           
Abdominal wall abscess  1  0/1007 (0.00%)  0/1003 (0.00%)  1/1009 (0.10%)  0/1007 (0.00%)  0/1003 (0.00%) 
Appendicitis  1  0/1007 (0.00%)  0/1003 (0.00%)  2/1009 (0.20%)  1/1007 (0.10%)  1/1003 (0.10%) 
Bartholin's abscess  1  0/1007 (0.00%)  0/1003 (0.00%)  2/1009 (0.20%)  0/1007 (0.00%)  0/1003 (0.00%) 
Breast abscess  1  0/1007 (0.00%)  1/1003 (0.10%)  0/1009 (0.00%)  1/1007 (0.10%)  0/1003 (0.00%) 
Disseminated tuberculosis  1  0/1007 (0.00%)  0/1003 (0.00%)  0/1009 (0.00%)  1/1007 (0.10%)  0/1003 (0.00%) 
Gastroenteritis  1  0/1007 (0.00%)  0/1003 (0.00%)  3/1009 (0.30%)  0/1007 (0.00%)  1/1003 (0.10%) 
Gingival abscess  1  0/1007 (0.00%)  0/1003 (0.00%)  1/1009 (0.10%)  0/1007 (0.00%)  0/1003 (0.00%) 
Malaria  1  0/1007 (0.00%)  1/1003 (0.10%)  1/1009 (0.10%)  2/1007 (0.20%)  0/1003 (0.00%) 
Meningitis  1  0/1007 (0.00%)  0/1003 (0.00%)  0/1009 (0.00%)  1/1007 (0.10%)  0/1003 (0.00%) 
Meningitis bacterial  1  0/1007 (0.00%)  1/1003 (0.10%)  0/1009 (0.00%)  0/1007 (0.00%)  0/1003 (0.00%) 
Meningitis viral  1  0/1007 (0.00%)  0/1003 (0.00%)  0/1009 (0.00%)  0/1007 (0.00%)  1/1003 (0.10%) 
Pelvic inflammatory disease  1  0/1007 (0.00%)  0/1003 (0.00%)  1/1009 (0.10%)  1/1007 (0.10%)  1/1003 (0.10%) 
Pericarditis tuberculous  1  0/1007 (0.00%)  0/1003 (0.00%)  1/1009 (0.10%)  0/1007 (0.00%)  0/1003 (0.00%) 
Pneumonia  1  0/1007 (0.00%)  0/1003 (0.00%)  1/1009 (0.10%)  0/1007 (0.00%)  0/1003 (0.00%) 
Postoperative wound infection  1  1/1007 (0.10%)  0/1003 (0.00%)  0/1009 (0.00%)  0/1007 (0.00%)  0/1003 (0.00%) 
Pulmonary tuberculosis  1  1/1007 (0.10%)  1/1003 (0.10%)  2/1009 (0.20%)  1/1007 (0.10%)  3/1003 (0.30%) 
Pyelonephritis  1  0/1007 (0.00%)  0/1003 (0.00%)  0/1009 (0.00%)  1/1007 (0.10%)  1/1003 (0.10%) 
Respiratory tract infection  1  0/1007 (0.00%)  1/1003 (0.10%)  0/1009 (0.00%)  0/1007 (0.00%)  1/1003 (0.10%) 
Sinusitis  1  0/1007 (0.00%)  0/1003 (0.00%)  1/1009 (0.10%)  0/1007 (0.00%)  1/1003 (0.10%) 
Skin infection  1  0/1007 (0.00%)  0/1003 (0.00%)  0/1009 (0.00%)  1/1007 (0.10%)  0/1003 (0.00%) 
Tonsillitis  1  0/1007 (0.00%)  0/1003 (0.00%)  0/1009 (0.00%)  1/1007 (0.10%)  0/1003 (0.00%) 
Tuberculosis  1  0/1007 (0.00%)  1/1003 (0.10%)  0/1009 (0.00%)  0/1007 (0.00%)  0/1003 (0.00%) 
Vulval abscess  1  0/1007 (0.00%)  0/1003 (0.00%)  1/1009 (0.10%)  0/1007 (0.00%)  0/1003 (0.00%) 
Wound sepsis  1  0/1007 (0.00%)  1/1003 (0.10%)  0/1009 (0.00%)  0/1007 (0.00%)  0/1003 (0.00%) 
Injury, poisoning and procedural complications           
Abdominal injury  1  0/1007 (0.00%)  0/1003 (0.00%)  0/1009 (0.00%)  1/1007 (0.10%)  0/1003 (0.00%) 
Ankle fracture  1  1/1007 (0.10%)  0/1003 (0.00%)  1/1009 (0.10%)  1/1007 (0.10%)  0/1003 (0.00%) 
Electric shock  1  0/1007 (0.00%)  0/1003 (0.00%)  0/1009 (0.00%)  1/1007 (0.10%)  0/1003 (0.00%) 
Foreign body  1  0/1007 (0.00%)  1/1003 (0.10%)  0/1009 (0.00%)  0/1007 (0.00%)  0/1003 (0.00%) 
Injury  1  0/1007 (0.00%)  1/1003 (0.10%)  1/1009 (0.10%)  1/1007 (0.10%)  0/1003 (0.00%) 
Internal injury  1  0/1007 (0.00%)  0/1003 (0.00%)  1/1009 (0.10%)  0/1007 (0.00%)  0/1003 (0.00%) 
Joint dislocation  1  0/1007 (0.00%)  1/1003 (0.10%)  0/1009 (0.00%)  0/1007 (0.00%)  0/1003 (0.00%) 
Laceration  1  1/1007 (0.10%)  0/1003 (0.00%)  0/1009 (0.00%)  0/1007 (0.00%)  0/1003 (0.00%) 
Lower limb fracture  1  2/1007 (0.20%)  0/1003 (0.00%)  0/1009 (0.00%)  0/1007 (0.00%)  0/1003 (0.00%) 
Overdose  1  0/1007 (0.00%)  1/1003 (0.10%)  0/1009 (0.00%)  0/1007 (0.00%)  0/1003 (0.00%) 
Pelvic fracture  1  0/1007 (0.00%)  0/1003 (0.00%)  1/1009 (0.10%)  0/1007 (0.00%)  0/1003 (0.00%) 
Stab wound  1  0/1007 (0.00%)  0/1003 (0.00%)  1/1009 (0.10%)  0/1007 (0.00%)  0/1003 (0.00%) 
Tendon injury  1  0/1007 (0.00%)  1/1003 (0.10%)  0/1009 (0.00%)  0/1007 (0.00%)  0/1003 (0.00%) 
Thermal burn  1  1/1007 (0.10%)  1/1003 (0.10%)  1/1009 (0.10%)  1/1007 (0.10%)  0/1003 (0.00%) 
Upper limb fracture  1  1/1007 (0.10%)  0/1003 (0.00%)  0/1009 (0.00%)  0/1007 (0.00%)  0/1003 (0.00%) 
Investigations           
Alanine aminotransferase increased  1  0/1007 (0.00%)  1/1003 (0.10%)  2/1009 (0.20%)  1/1007 (0.10%)  0/1003 (0.00%) 
Aspartate aminotransferase increased  1  0/1007 (0.00%)  1/1003 (0.10%)  0/1009 (0.00%)  1/1007 (0.10%)  0/1003 (0.00%) 
Metabolism and nutrition disorders           
Diabetes mellitus  1  0/1007 (0.00%)  0/1003 (0.00%)  0/1009 (0.00%)  0/1007 (0.00%)  2/1003 (0.20%) 
Musculoskeletal and connective tissue disorders           
Back pain  1  0/1007 (0.00%)  0/1003 (0.00%)  0/1009 (0.00%)  0/1007 (0.00%)  2/1003 (0.20%) 
Musculoskeletal chest pain  1  0/1007 (0.00%)  0/1003 (0.00%)  0/1009 (0.00%)  1/1007 (0.10%)  0/1003 (0.00%) 
Rheumatoid arthritis  1  0/1007 (0.00%)  0/1003 (0.00%)  0/1009 (0.00%)  0/1007 (0.00%)  1/1003 (0.10%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Gliomatosis cerebri  1  0/1007 (0.00%)  0/1003 (0.00%)  1/1009 (0.10%)  0/1007 (0.00%)  0/1003 (0.00%) 
Lipoma  1  0/1007 (0.00%)  0/1003 (0.00%)  1/1009 (0.10%)  0/1007 (0.00%)  0/1003 (0.00%) 
Uterine leiomyoma  1  0/1007 (0.00%)  0/1003 (0.00%)  0/1009 (0.00%)  1/1007 (0.10%)  0/1003 (0.00%) 
Nervous system disorders           
Cerebral infarction  1  1/1007 (0.10%)  0/1003 (0.00%)  0/1009 (0.00%)  0/1007 (0.00%)  0/1003 (0.00%) 
Cerebrovascular accident  1  0/1007 (0.00%)  0/1003 (0.00%)  1/1009 (0.10%)  0/1007 (0.00%)  0/1003 (0.00%) 
Epilepsy  1  0/1007 (0.00%)  0/1003 (0.00%)  1/1009 (0.10%)  0/1007 (0.00%)  0/1003 (0.00%) 
Headache  1  2/1007 (0.20%)  2/1003 (0.20%)  1/1009 (0.10%)  4/1007 (0.40%)  1/1003 (0.10%) 
Loss of consciousness  1  0/1007 (0.00%)  1/1003 (0.10%)  0/1009 (0.00%)  0/1007 (0.00%)  0/1003 (0.00%) 
Meningism  1  0/1007 (0.00%)  1/1003 (0.10%)  0/1009 (0.00%)  0/1007 (0.00%)  0/1003 (0.00%) 
Migraine  1  0/1007 (0.00%)  1/1003 (0.10%)  1/1009 (0.10%)  0/1007 (0.00%)  0/1003 (0.00%) 
Optic neuritis  1  0/1007 (0.00%)  0/1003 (0.00%)  0/1009 (0.00%)  0/1007 (0.00%)  1/1003 (0.10%) 
Syncope  1  1/1007 (0.10%)  0/1003 (0.00%)  0/1009 (0.00%)  0/1007 (0.00%)  0/1003 (0.00%) 
Transient ischaemic attack  1  0/1007 (0.00%)  1/1003 (0.10%)  1/1009 (0.10%)  0/1007 (0.00%)  0/1003 (0.00%) 
Pregnancy, puerperium and perinatal conditions           
Abortion threatened  1  0/1007 (0.00%)  0/1003 (0.00%)  1/1009 (0.10%)  0/1007 (0.00%)  0/1003 (0.00%) 
Ectopic pregnancy  1  0/1007 (0.00%)  1/1003 (0.10%)  1/1009 (0.10%)  1/1007 (0.10%)  0/1003 (0.00%) 
Haemorrhage in pregnancy  1  2/1007 (0.20%)  4/1003 (0.40%)  4/1009 (0.40%)  3/1007 (0.30%)  2/1003 (0.20%) 
Hyperemesis gravidarum  1  0/1007 (0.00%)  0/1003 (0.00%)  0/1009 (0.00%)  1/1007 (0.10%)  0/1003 (0.00%) 
Intrapartum haemorrhage  1  0/1007 (0.00%)  0/1003 (0.00%)  1/1009 (0.10%)  0/1007 (0.00%)  0/1003 (0.00%) 
Post abortion haemorrhage  1  0/1007 (0.00%)  4/1003 (0.40%)  2/1009 (0.20%)  1/1007 (0.10%)  2/1003 (0.20%) 
Pre-eclampsia  1  0/1007 (0.00%)  1/1003 (0.10%)  0/1009 (0.00%)  0/1007 (0.00%)  0/1003 (0.00%) 
Premature labour  1  0/1007 (0.00%)  2/1003 (0.20%)  5/1009 (0.50%)  1/1007 (0.10%)  1/1003 (0.10%) 
Premature rupture of membranes  1  0/1007 (0.00%)  0/1003 (0.00%)  2/1009 (0.20%)  0/1007 (0.00%)  0/1003 (0.00%) 
Retained products of conception  1  0/1007 (0.00%)  0/1003 (0.00%)  1/1009 (0.10%)  0/1007 (0.00%)  1/1003 (0.10%) 
Psychiatric disorders           
Bipolar disorder  1  0/1007 (0.00%)  1/1003 (0.10%)  0/1009 (0.00%)  0/1007 (0.00%)  0/1003 (0.00%) 
Depression  1  0/1007 (0.00%)  0/1003 (0.00%)  0/1009 (0.00%)  1/1007 (0.10%)  0/1003 (0.00%) 
Depression suicidal  1  0/1007 (0.00%)  0/1003 (0.00%)  1/1009 (0.10%)  0/1007 (0.00%)  0/1003 (0.00%) 
Intentional self-injury  1  0/1007 (0.00%)  1/1003 (0.10%)  0/1009 (0.00%)  0/1007 (0.00%)  1/1003 (0.10%) 
Suicidal ideation  1  0/1007 (0.00%)  1/1003 (0.10%)  0/1009 (0.00%)  0/1007 (0.00%)  0/1003 (0.00%) 
Suicide attempt  1  0/1007 (0.00%)  2/1003 (0.20%)  1/1009 (0.10%)  0/1007 (0.00%)  0/1003 (0.00%) 
Renal and urinary disorders           
Urinary tract obstruction  1  0/1007 (0.00%)  0/1003 (0.00%)  0/1009 (0.00%)  0/1007 (0.00%)  1/1003 (0.10%) 
Reproductive system and breast disorders           
Bartholin's cyst  1  0/1007 (0.00%)  0/1003 (0.00%)  1/1009 (0.10%)  0/1007 (0.00%)  0/1003 (0.00%) 
Breast discharge  1  0/1007 (0.00%)  0/1003 (0.00%)  0/1009 (0.00%)  1/1007 (0.10%)  0/1003 (0.00%) 
Breast enlargement  1  0/1007 (0.00%)  0/1003 (0.00%)  0/1009 (0.00%)  1/1007 (0.10%)  0/1003 (0.00%) 
Menorrhagia  1  0/1007 (0.00%)  0/1003 (0.00%)  1/1009 (0.10%)  0/1007 (0.00%)  0/1003 (0.00%) 
Metrorrhagia  1  0/1007 (0.00%)  0/1003 (0.00%)  0/1009 (0.00%)  1/1007 (0.10%)  0/1003 (0.00%) 
Pelvic pain  1  1/1007 (0.10%)  0/1003 (0.00%)  0/1009 (0.00%)  0/1007 (0.00%)  0/1003 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Asthma  1  0/1007 (0.00%)  1/1003 (0.10%)  2/1009 (0.20%)  0/1007 (0.00%)  0/1003 (0.00%) 
Dyspnoea  1  0/1007 (0.00%)  0/1003 (0.00%)  1/1009 (0.10%)  1/1007 (0.10%)  0/1003 (0.00%) 
Epistaxis  1  0/1007 (0.00%)  0/1003 (0.00%)  1/1009 (0.10%)  0/1007 (0.00%)  0/1003 (0.00%) 
Vascular disorders           
Deep vein thrombosis  1  1/1007 (0.10%)  0/1003 (0.00%)  0/1009 (0.00%)  0/1007 (0.00%)  0/1003 (0.00%) 
Hypertension  1  0/1007 (0.00%)  1/1003 (0.10%)  1/1009 (0.10%)  0/1007 (0.00%)  0/1003 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (12.1-16.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
Oral TDF Oral TDF-FTC Oral Placebo TFV Gel Gel Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   646/1007 (64.15%)   740/1003 (73.78%)   747/1009 (74.03%)   705/1007 (70.01%)   715/1003 (71.29%) 
Infections and infestations           
Genitourinary chlamydia infection  1  105/1007 (10.43%)  144/1003 (14.36%)  154/1009 (15.26%)  100/1007 (9.93%)  107/1003 (10.67%) 
Genitourinary tract gonococcal infection  1  26/1007 (2.58%)  46/1003 (4.59%)  45/1009 (4.46%)  40/1007 (3.97%)  32/1003 (3.19%) 
Urinary tract infection  1  26/1007 (2.58%)  40/1003 (3.99%)  43/1009 (4.26%)  28/1007 (2.78%)  36/1003 (3.59%) 
Vaginitis bacterial  1  31/1007 (3.08%)  41/1003 (4.09%)  41/1009 (4.06%)  32/1007 (3.18%)  43/1003 (4.29%) 
Vulvovaginal candidiasis  1  43/1007 (4.27%)  58/1003 (5.78%)  54/1009 (5.35%)  59/1007 (5.86%)  51/1003 (5.08%) 
Vulvovaginitis trichomonal  1  62/1007 (6.16%)  65/1003 (6.48%)  66/1009 (6.54%)  46/1007 (4.57%)  55/1003 (5.48%) 
Investigations           
Alanine aminotransferase increased  1  90/1007 (8.94%)  99/1003 (9.87%)  116/1009 (11.50%)  90/1007 (8.94%)  84/1003 (8.37%) 
Aspartate aminotransferase increased  1  69/1007 (6.85%)  87/1003 (8.67%)  88/1009 (8.72%)  73/1007 (7.25%)  58/1003 (5.78%) 
Blood phosphorus decreased  1  29/1007 (2.88%)  26/1003 (2.59%)  34/1009 (3.37%)  40/1007 (3.97%)  29/1003 (2.89%) 
Haemoglobin decreased  1  20/1007 (1.99%)  38/1003 (3.79%)  44/1009 (4.36%)  27/1007 (2.68%)  29/1003 (2.89%) 
Metabolism and nutrition disorders           
Hypophosphataemia  1  171/1007 (16.98%)  180/1003 (17.95%)  184/1009 (18.24%)  188/1007 (18.67%)  169/1003 (16.85%) 
Nervous system disorders           
Headache  1  32/1007 (3.18%)  39/1003 (3.89%)  44/1009 (4.36%)  23/1007 (2.28%)  30/1003 (2.99%) 
Renal and urinary disorders           
Dysuria  1  143/1007 (14.20%)  159/1003 (15.85%)  176/1009 (17.44%)  170/1007 (16.88%)  188/1003 (18.74%) 
Pollakiuria  1  16/1007 (1.59%)  39/1003 (3.89%)  41/1009 (4.06%)  30/1007 (2.98%)  34/1003 (3.39%) 
Proteinuria  1  154/1007 (15.29%)  203/1003 (20.24%)  180/1009 (17.84%)  165/1007 (16.39%)  183/1003 (18.25%) 
Reproductive system and breast disorders           
Cervical dysplasia  1  34/1007 (3.38%)  100/1003 (9.97%)  90/1009 (8.92%)  48/1007 (4.77%)  49/1003 (4.89%) 
Menorrhagia  1  16/1007 (1.59%)  21/1003 (2.09%)  29/1009 (2.87%)  33/1007 (3.28%)  26/1003 (2.59%) 
Metrorrhagia  1  29/1007 (2.88%)  55/1003 (5.48%)  50/1009 (4.96%)  48/1007 (4.77%)  51/1003 (5.08%) 
Pelvic pain  1  31/1007 (3.08%)  46/1003 (4.59%)  52/1009 (5.15%)  56/1007 (5.56%)  52/1003 (5.18%) 
Vaginal discharge  1  100/1007 (9.93%)  129/1003 (12.86%)  124/1009 (12.29%)  119/1007 (11.82%)  122/1003 (12.16%) 
Vulvovaginal pruritus  1  56/1007 (5.56%)  75/1003 (7.48%)  80/1009 (7.93%)  150/1007 (14.90%)  126/1003 (12.56%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (12.1-16.0)
In September 2011, the oral TDF arm was discontinued for futility; in November 2011, the TFV gel and gel placebo arms were discontinued for futility. The TDF-FTC and oral placebo arms continued follow-up until the end of study in August 2012.
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: Jeanne Marrazzo, MD, MPH, FACP, FIDSA
Organization: University of Washington
Phone: 206-744-3679
EMail: jmm2@uw.edu
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: NCT00705679     History of Changes
Other Study ID Numbers: MTN-003 (VOICE)
10622 ( Registry Identifier: DAIDS ES )
MTN-003 ( Other Identifier: Microbicide Trials Network )
5U01AI068633-05 ( U.S. NIH Grant/Contract )
VOICE ( Other Identifier: Microbicide Trials Network )
First Submitted: June 24, 2008
First Posted: June 26, 2008
Results First Submitted: January 12, 2016
Results First Posted: February 10, 2016
Last Update Posted: March 14, 2016