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

This study has been completed.
Sponsor:
Collaborator:
Microbicide Trials Network
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00705679
First received: June 24, 2008
Last updated: February 15, 2016
Last verified: February 2016
Results First Received: January 12, 2016  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Pharmacokinetics Study;   Intervention Model: Parallel Assignment;   Masking: 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

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Women were recruited from September 2009 through June 2011 from 15 sites in South Africa, Uganda, and Zimbabwe.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

Reporting Groups
  Description
Oral TDF

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

Oral TDF-FTC

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

Oral Placebo

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

TFV Gel

Application of tenofovir 1% vaginal gel once daily

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

Gel Placebo

Application of tenofovir placebo gel once daily

Tenofovir placebo: placebo gel


Participant Flow:   Overall Study
    Oral TDF   Oral TDF-FTC   Oral Placebo   TFV Gel   Gel Placebo
STARTED   1007   1003   1009   1007   1003 
COMPLETED   942   864   894   927   934 
NOT COMPLETED   65   139   115   80   69 
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 



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Includes all participants enrolled and randomized to a study arm

Reporting Groups
  Description
Oral TDF

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

Oral TDF-FTC

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

Oral Placebo

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

TFV Gel

Application of tenofovir 1% vaginal gel once daily

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

Gel Placebo

Application of tenofovir placebo gel once daily

Tenofovir placebo: placebo gel

Total Total of all reporting groups

Baseline Measures
   Oral TDF   Oral TDF-FTC   Oral Placebo   TFV Gel   Gel Placebo   Total 
Overall Participants Analyzed 
[Units: Participants]
 1007   1003   1009   1007   1003   5029 
Age 
[Units: Years]
Mean (Standard Deviation)
 25.5  (5.1)   25.2  (5.2)   25.3  (5.2)   25.3  (5.2)   25.3  (5.1)   25.3  (5.2) 
Gender 
[Units: Participants]
           
Female   1007   1003   1009   1007   1003   5029 
Male   0   0   0   0   0   0 
Race/Ethnicity, Customized [1] 
[Units: 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] Response to the question: What is your ethnic group or tribe?
Region of Enrollment [1] 
[Units: Participants]
           
South Africa   816   812   815   818   816   4077 
Uganda   64   64   65   65   64   322 
Zimbabwe   127   127   129   124   123   630 
[1] Country at time of enrollment
Some secondary school education or higher [1] 
[Units: 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] Response to question: What is your highest level of education?
Earns own income [1] 
[Units: Participants]
           
Yes   569   569   586   587   570   2881 
No   438   434   423   420   432   2147 
Missing   0   0   0   0   1   1 
[1] Response to question: Do you earn an income of your own?
Live births [1] 
[Units: Children]
Mean (Standard Deviation)
 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] Response to question: How many children have you given birth to who were alive at birth?
Currently married [1] 
[Units: Participants]
           
Yes   207   209   211   210   215   1052 
No   800   794   798   797   788   3977 
[1] Response to question: Are you currently married?
At least 2 male sex partners in the past 3 months [1] 
[Units: Participants]
           
Yes   236   208   244   217   199   1104 
No   761   782   754   779   793   3869 
No response   10   13   11   11   11   56 
[1] 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 
[Units: Episodes]
Mean (Standard Deviation)
 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 
[Units: 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] 
[Units: Participants]
           
Yes   164   175   174   179   176   868 
No   827   812   823   814   810   4086 
Missing   16   16   12   14   17   75 
[1] 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] 
[Units: Participants]
           
Yes   709   723   700   707   726   3565 
No   298   280   309   300   277   1464 
[1] 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] 
[Units: Participants]
           
Yes   226   223   238   238   215   1140 
No   781   780   771   769   788   3889 
[1] 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] 
[Units: Participants]
           
Yes   122   117   127   116   129   611 
No   884   886   882   891   874   4417 
Missing   1   0   0   0   0   1 
[1] Testing was performed with the use of a strand-displacement amplification assay
Infection by Neisseria gonorrhoeae [1] 
[Units: Participants]
           
Yes   42   27   34   24   36   163 
No   964   976   975   983   967   4865 
Missing   1   0   0   0   0   1 
[1] Testing was performed with the use of a strand-displacement amplification assay
Infection by Trichomonas vaginalis [1] 
[Units: Participants]
           
Yes   68   54   66   62   51   301 
No   939   948   943   943   949   4722 
Missing   0   1   0   2   3   6 
[1] Testing was performed with the use of the OSOM Trichomonas Rapid Test
Syphilis infection [1] 
[Units: Participants]
           
Yes   12   15   16   14   11   68 
No   994   988   993   993   992   4960 
Missing   1   0   0   0   0   1 
[1] Testing was performed with the use of a rapid plasma reagin screening test followed by a confirmatory microhemagglutinin assay
HSV-2 infection [1] 
[Units: Participants]
           
Yes   482   449   455   438   465   2289 
No   520   548   551   566   531   2716 
Missing   5   6   3   3   7   24 
[1] 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] 
[Units: Participants]
           
Yes   422   410   401   397   393   2023 
No   578   592   607   606   604   2987 
Missing   7   1   1   4   6   19 
[1] Bacterial vaginosis was determined by the Nugent score on Gram's staining of vaginal fluid (Nugent score 7-10).


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Person-years of Follow-up of Tenofovir 1% Gel and Vaginal Placebo Gel Arms   [ Time Frame: For up to 30 months of follow-up ]

2.  Primary:   Number of HIV-1 Infections of Tenofovir 1% Gel and Vaginal Placebo Gel Arms   [ Time Frame: For up to 30 months of follow-up ]

3.  Primary:   Incidence Rate of HIV-1 Infections of Tenofovir 1% Gel and Vaginal Placebo Gel Arms   [ Time Frame: For up to 30 months of follow-up ]

4.  Primary:   Person-years of Follow-up of Oral TDF and Oral Placebo Arms   [ Time Frame: For up to 30 months of follow-up ]

5.  Primary:   Number of HIV-1 Infections of Oral TDF and Oral Placebo Arms   [ Time Frame: For up to 30 months of follow-up ]

6.  Primary:   Incidence Rate of HIV-1 Infections of Oral TDF and Oral Placebo Arms   [ Time Frame: For up to 30 months of follow-up ]

7.  Primary:   Person-years of Follow-up of Oral TDF-FTC and Oral Placebo Arms   [ Time Frame: For up to 30 months of follow-up ]

8.  Primary:   Number of HIV-1 Infections of Oral TDF-FTC and Oral Placebo Arms   [ Time Frame: For up to 30 months of follow-up ]

9.  Primary:   Incidence Rate of HIV-1 Infections of Oral TDF-FTC and Oral Placebo Arms   [ Time Frame: For up to 30 months of follow-up ]

10.  Primary:   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   [ Time Frame: Throughout study, up to 2.5 years ]

11.  Secondary:   Frequency of HIV-1 Drug Resistance in Women Who Acquire HIV-1 Infection While Using Study Product   [ Time Frame: Throughout study, up to 2.5 years ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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.


  More Information
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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
e-mail: jmm2@uw.edu


Publications:
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 ( US NIH Grant/Contract Award Number )
VOICE ( Other Identifier: Microbicide Trials Network )
Study First Received: June 24, 2008
Results First Received: January 12, 2016
Last Updated: February 15, 2016
Health Authority: United States: Food and Drug Administration