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.
Name: Emtricitabine/tenofovir disoproxil fumarate
Description: 200 mg/300 mg tabletType: Drug2
Name: Emtricitabine/tenofovir disoproxil fumarate placebo
Description: placebo tabletType: Drug1 3
Name: Tenofovir disoproxil fumarate
Description: 300 mg tabletType: Drug1
Name: Tenofovir disoproxil fumarate placebo
Description: placebo tabletType: Drug2 3
Name: Tenofovir 1% vaginal gel
Description: 1 gm/100 ml of 1% gelType: Drug4
Name: Tenofovir placebo
Description: placebo gelType: Drug5
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.
Measure: Person-years of Follow-up of Tenofovir 1% Gel and Vaginal Placebo Gel Arms Time: For up to 30 months of follow-upDescription: 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).
Measure: Number of HIV-1 Infections of Tenofovir 1% Gel and Vaginal Placebo Gel Arms Time: For up to 30 months of follow-upDescription: 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).
Measure: Incidence Rate of HIV-1 Infections of Tenofovir 1% Gel and Vaginal Placebo Gel Arms Time: For up to 30 months of follow-upDescription: 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.
Measure: Person-years of Follow-up of Oral TDF and Oral Placebo Arms Time: For up to 30 months of follow-upDescription: 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).
Measure: Number of HIV-1 Infections of Oral TDF and Oral Placebo Arms Time: For up to 30 months of follow-upDescription: 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).
Measure: Incidence Rate of HIV-1 Infections of Oral TDF and Oral Placebo Arms Time: For up to 30 months of follow-upDescription: 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.
Measure: Person-years of Follow-up of Oral TDF-FTC and Oral Placebo Arms Time: For up to 30 months of follow-upDescription: 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).
Measure: Number of HIV-1 Infections of Oral TDF-FTC and Oral Placebo Arms Time: For up to 30 months of follow-upDescription: 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).
Measure: Incidence Rate of HIV-1 Infections of Oral TDF-FTC and Oral Placebo Arms Time: For up to 30 months of follow-upDescription: 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.
Measure: 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: Throughout study, up to 2.5 yearsDescription: 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.
Measure: Frequency of HIV-1 Drug Resistance in Women Who Acquire HIV-1 Infection While Using Study Product Time: Throughout study, up to 2.5 yearsAllocation: Randomized
Parallel Assignment
There are 4 SNPs
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 ---
K65R, K70E, and M184I were not detected in HIV-1 from any HIV-1 seroconverters while on study product. --- K65R ---
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 ---
K65R, K70E, and M184I were not detected in HIV-1 from any HIV-1 seroconverters while on study product. --- K65R --- --- K70E ---
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 --- --- M184I ---
K65R, K70E, and M184I were not detected in HIV-1 from any HIV-1 seroconverters while on study product. --- K65R --- --- K70E --- --- M184I ---
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 --- --- M184I --- --- M184V ---
The number of HIV-1 seroconverters while on study with the M184V resistance mutation are reported for this outcome measure.. 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. --- M184V ---