Clinical Trials

MainTitle

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

This study has been completed
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

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
History of Changes
Purpose

Purpose

A new approach to HIV prevention currently being studied includes the use of microbicides, substances that kill microbes. Tenofovir disoproxil fumarate (TDF) and emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) are oral, FDA-approved, anti-HIV drugs, and tenofovir gel is an experimental microbicide. The purpose of this study is to determine the safety and effectiveness of daily tenofovir 1% gel compared to a vaginal placebo gel, and the safety and effectiveness of oral TDF and oral FTC/TDF compared to an oral placebo in preventing HIV infection among women at risk for sexually transmitted infections.

Condition Intervention Phase
HIV Infections

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
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Phase 2B Safety and Effectiveness Study of Tenofovir 1% Gel, Tenofovir Disproxil Fumarate Tablet and Emtricitabine/Tenofovir Disoproxil Fumarate Tablet for the Prevention of HIV Infection in Women

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures

  • Person-years of Follow-up of Tenofovir 1% Gel and Vaginal Placebo Gel Arms [ Time Frame: For up to 30 months of follow-up ]
    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.
  • Number of HIV-1 Infections of Tenofovir 1% Gel and Vaginal Placebo Gel Arms [ Time Frame: For up to 30 months of follow-up ]
    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).
  • 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 ]
    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).
  • Person-years of Follow-up of Oral TDF and Oral Placebo Arms [ Time Frame: For up to 30 months of follow-up ]
    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.
  • Number of HIV-1 Infections of Oral TDF and Oral Placebo Arms [ Time Frame: For up to 30 months of follow-up ]
    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).
  • Incidence Rate of HIV-1 Infections of Oral TDF and Oral Placebo Arms [ Time Frame: For up to 30 months of follow-up ]
    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).
  • Person-years of Follow-up of Oral TDF-FTC and Oral Placebo Arms [ Time Frame: For up to 30 months of follow-up ]
    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.
  • Number of HIV-1 Infections of Oral TDF-FTC and Oral Placebo Arms [ Time Frame: For up to 30 months of follow-up ]
    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).
  • Incidence Rate of HIV-1 Infections of Oral TDF-FTC and Oral Placebo Arms [ Time Frame: For up to 30 months of follow-up ]
    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).
  • 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 ]
    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.
Secondary Outcome Measures:
  • 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 ]
    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.

Enrollment: 5029
Study Start Date: August 2009
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: 1
TDF 300 mg tablet taken orally once daily and one FTC/TDF placebo tablet taken orally once daily for 12 to 36 months
Drug: Emtricitabine/tenofovir disoproxil fumarate placebo

placebo tablet

Other Name:
  • FTC/TDF placebo
  • Truvada placebo

Drug: Tenofovir disoproxil fumarate

300 mg tablet

Other Name: TDF
Experimental: 2
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
Drug: Emtricitabine/tenofovir disoproxil fumarate

200 mg/300 mg tablet

Other Name:
  • FTC/TDF
  • Truvada

Drug: Tenofovir disoproxil fumarate placebo

placebo tablet

Other Name: TDF placebo
Experimental: 3
TDF placebo tablet taken orally once daily and one FTC/TDF placebo tablet taken orally once daily for 12 to 36 months
Drug: Emtricitabine/tenofovir disoproxil fumarate placebo

placebo tablet

Other Name:
  • FTC/TDF placebo
  • Truvada placebo

Drug: Tenofovir disoproxil fumarate placebo

placebo tablet

Other Name: TDF placebo
Experimental: 4
Application of tenofovir 1% vaginal gel once daily
Drug: Tenofovir 1% vaginal gel

1 gm/100 ml of 1% gel

Other Name:
  • TFV
  • 9-[2-(Phosphonomethoxy)propyl]adenine

Experimental: 5
Application of tenofovir placebo gel once daily
Drug: Tenofovir placebo

placebo gel

Other Name: TFV placebo

Detailed Description:

It is necessary to monitor both the adherence and blood levels of microbicides in order to gauge its efficacy in a study population. Utilizing an experimental microbicide (tenofovir gel) and anti-HIV drugs (TDF, FTC/TDF), this study will measure the effectiveness and safety to and blood levels of the three interventions in three regimens given to HIV uninfected women.
The expected duration of participation for each participant ranges from a minimum of 12 months to a maximum of 38 months. Study participants will be randomly assigned into one of five study groups, each with a different regimen. Group 1 participants will take one TDF tablet daily and one FTC/TDF placebo tablet daily. Group 2 participants will take one TDF placebo tablet daily and one FTC/TDF tablet daily. Group 3 participants will take one TDF placebo tablet daily and one FTC/TDF placebo tablet daily. Group 4 participants will apply tenofovir 1% gel vaginally once daily. Group 5 participants will apply tenofovir 1% placebo gel vaginally once daily.
Study visits will occur every 28 days after enrollment. Medical history, a physical exam, behavioral and adherence assessment, urine and blood collection, and counseling will occur at all visits. Blood will also be collected and archived for future research at select visits. Pharmacokinetic studies will occur at some visits. A pap smear will occur at select visits. Some participants may have hair samples collected on an optional basis at study visits every 2 months.

Eligibility

Eligibility

Ages Eligible for Study: 18 Years to 45 Years  
Sexes Eligible for Study: Female  
Accepts Healthy Volunteers: Yes  

Criteria

Inclusion Criteria:

  • Willing to provide adequate locator information
  • Sexually active, defined as having vaginal intercourse at least once in the 3 months prior to screening
  • Agree to not participate in other research studies involving drugs, medical devices, or vaginal products for duration of study.
  • Agree to use effective method of contraception. More information on this criterion can be found in the protocol.


Exclusion Criteria:
  • HIV infected
  • Known adverse reaction to any of the study products
  • Known adverse reaction to latex
  • Pathologic bone fracture not related to trauma
  • Non-therapeutic injection drug use in the 12 months prior to screening
  • Post-exposure prophylaxis for HIV exposure within 6 months prior to enrollment
  • Last pregnancy outcome 42 days or less prior to enrollment
  • Gynecologic or genital procedure 42 days or less prior to enrollment
  • Participation in any other research study involving drugs, medical devices, or vaginal products 30 days or less prior to enrollment
  • Currently using spermicide, interferon or interleukin therapy, or certain medications. More information on this criterion can be found in the protocol.
  • Any significant uncontrolled active or chronic disease. More information on this criterion can be found in the protocol.
  • Certain abnormal laboratory values. More information on this criterion can be found in the protocol.
  • Intends to become pregnant in the 24 months after enrollment
  • Plans to relocate or travel away from the study site for more than 8 consecutive weeks in the 24 months after enrollment
  • Urinary tract infection
  • Pelvic inflammatory disease, an STI, or reproductive tract infection requiring treatment
  • Grade 2 or higher pelvic exam finding
  • Any condition that, in the opinion of the investigator, would interfere with the study
  • Pregnant or breastfeeding

contacts and locations

Contacts and Locations

Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00705679

Locations

South Africa
Wits Reproductive Health and HIV Institute CRS (WRHI CRS)
Johannesburg, Gauteng, South Africa, 2001
Soweto MTN CRS
Johannesburg, Gauteng, South Africa
Overport CRS
Asherville, KwaZulu-Natal, South Africa, 4091
Chatsworth CRS
Chatsworth, KwaZulu-Natal, South Africa, 4030
eThekwini CRS
Durban, KwaZulu-Natal, South Africa, 4001
Tongaat CRS
Tongaat, KwaZulu-Natal, South Africa, 4400
Umkomaas CRS
Umkomaas, KwaZulu-Natal, South Africa, 4170
Verulam CRS
Verulam, KwaZulu-Natal, South Africa, 4340
Botha's Hill CRS
Westville, KwaZulu-Natal, South Africa, 3630
Isipingo CRS
Westville, KwaZulu-Natal, South Africa, 3630
CAPRISA Aurum CRS
Klerksdorp, South Africa, 2571
Uganda
MU-JHU Research Collaboration CRS
Kampala, Uganda
Zimbabwe
Seke South CRS
Chitungwiza, Zimbabwe
Zengeza CRS
Chitungwiza, Zimbabwe
Spilhaus CRS
Harare, Zimbabwe

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)
Microbicide Trials Network

Investigators

Study Chair: Zvavahera M. Chirenje, MD, FRCOG UZ-UCSF Collaborative Research Programme
Study Chair: Jeanne Marrazzo, MD, MPH University of Washington, Division of Allergy and Infectious Disease
More Information

More Information

Additional Information:

Click here for the Microbicide Trials Network Web site

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  
  MTN-003  
  5U01AI068633-05  
  VOICE  
Study First Received: June 24, 2008  
Last Updated: February 15, 2016  

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Microbicide
HIV Seronegativity

Additional relevant MeSH terms:
Infection
HIV Infections
Acquired Immunodeficiency Syndrome
Tenofovir
Emtricitabine
Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

ClinicalTrials.gov processed this data on July 22, 2019
This information is provided by ClinicalTrials.gov.