HIV Infections
Conditions
Keywords
Microbicide, HIV Seronegativity
Brief summary
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.
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.
Interventions
DRUGEmtricitabine/tenofovir disoproxil fumarate
200 mg/300 mg tablet
placebo tablet
DRUGTenofovir disoproxil fumarate
300 mg tablet
placebo tablet
1 gm/100 ml of 1% gel
DRUGTenofovir placebo
placebo gel
Sponsors
Microbicide Trials Network
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
| Person-years of Follow-up of Tenofovir 1% Gel and Vaginal Placebo Gel Arms | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of HIV-1 Drug Resistance in Women Who Acquire HIV-1 Infection While Using Study Product | 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. |
Countries
South Africa, Uganda, Zimbabwe
Participant flow
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.
Participants by arm
| Arm | Count |
|---|---|
| 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 | 1,007 |
| 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 | 1,003 |
| 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 | 1,009 |
| TFV Gel Application of tenofovir 1% vaginal gel once daily
Tenofovir 1% vaginal gel: 1 gm/100 ml of 1% gel | 1,007 |
| Gel Placebo Application of tenofovir placebo gel once daily
Tenofovir placebo: placebo gel | 1,003 |
| Total | 5,029 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 0 | 0 | 0 |
| Overall Study | Death | 0 | 0 | 3 | 2 | 1 |
| Overall Study | Lost to Follow-up | 32 | 60 | 44 | 30 | 35 |
| Overall Study | Physician Decision | 0 | 1 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 32 | 77 | 68 | 47 | 33 |
Baseline characteristics
| Characteristic | Total | Gel Placebo | TFV Gel | Oral Placebo | Oral TDF-FTC | Oral TDF |
|---|---|---|---|---|---|---|
| Age, Continuous | 25.3 years STANDARD_DEVIATION 5.2 | 25.3 years STANDARD_DEVIATION 5.1 | 25.3 years STANDARD_DEVIATION 5.2 | 25.3 years STANDARD_DEVIATION 5.2 | 25.2 years STANDARD_DEVIATION 5.2 | 25.5 years STANDARD_DEVIATION 5.1 |
| Anal sex in the previous 3 months Missing | 75 participants | 17 participants | 14 participants | 12 participants | 16 participants | 16 participants |
| Anal sex in the previous 3 months No | 4086 participants | 810 participants | 814 participants | 823 participants | 812 participants | 827 participants |
| Anal sex in the previous 3 months Yes | 868 participants | 176 participants | 179 participants | 174 participants | 175 participants | 164 participants |
| At least 2 male sex partners in the past 3 months No | 3869 participants | 793 participants | 779 participants | 754 participants | 782 participants | 761 participants |
| At least 2 male sex partners in the past 3 months No response | 56 participants | 11 participants | 11 participants | 11 participants | 13 participants | 10 participants |
| At least 2 male sex partners in the past 3 months Yes | 1104 participants | 199 participants | 217 participants | 244 participants | 208 participants | 236 participants |
| Bacterial vaginosis infection Missing | 19 participants | 6 participants | 4 participants | 1 participants | 1 participants | 7 participants |
| Bacterial vaginosis infection No | 2987 participants | 604 participants | 606 participants | 607 participants | 592 participants | 578 participants |
| Bacterial vaginosis infection Yes | 2023 participants | 393 participants | 397 participants | 401 participants | 410 participants | 422 participants |
| Condom use during last vaginal intercourse Missing | 12 participants | 2 participants | 0 participants | 4 participants | 4 participants | 2 participants |
| Condom use during last vaginal intercourse No | 1251 participants | 268 participants | 239 participants | 263 participants | 239 participants | 242 participants |
| Condom use during last vaginal intercourse Yes | 3766 participants | 733 participants | 768 participants | 742 participants | 760 participants | 763 participants |
| Currently married No | 3977 participants | 788 participants | 797 participants | 798 participants | 794 participants | 800 participants |
| Currently married Yes | 1052 participants | 215 participants | 210 participants | 211 participants | 209 participants | 207 participants |
| Earns own income Missing | 1 participants | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Earns own income No | 2147 participants | 432 participants | 420 participants | 423 participants | 434 participants | 438 participants |
| Earns own income Yes | 2881 participants | 570 participants | 587 participants | 586 participants | 569 participants | 569 participants |
| Episodes of vaginal intercourse in the past 7 days | 2.5 episodes STANDARD_DEVIATION 3.1 | 2.6 episodes STANDARD_DEVIATION 2.9 | 2.6 episodes STANDARD_DEVIATION 3.6 | 2.5 episodes STANDARD_DEVIATION 2.6 | 2.5 episodes STANDARD_DEVIATION 3.4 | 2.5 episodes STANDARD_DEVIATION 2.8 |
| HSV-2 infection Missing | 24 participants | 7 participants | 3 participants | 3 participants | 6 participants | 5 participants |
| HSV-2 infection No | 2716 participants | 531 participants | 566 participants | 551 participants | 548 participants | 520 participants |
| HSV-2 infection Yes | 2289 participants | 465 participants | 438 participants | 455 participants | 449 participants | 482 participants |
| Infection by Chlamydia trachomatis Missing | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants |
| Infection by Chlamydia trachomatis No | 4417 participants | 874 participants | 891 participants | 882 participants | 886 participants | 884 participants |
| Infection by Chlamydia trachomatis Yes | 611 participants | 129 participants | 116 participants | 127 participants | 117 participants | 122 participants |
| Infection by Neisseria gonorrhoeae Missing | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants |
| Infection by Neisseria gonorrhoeae No | 4865 participants | 967 participants | 983 participants | 975 participants | 976 participants | 964 participants |
| Infection by Neisseria gonorrhoeae Yes | 163 participants | 36 participants | 24 participants | 34 participants | 27 participants | 42 participants |
| Infection by Trichomonas vaginalis Missing | 6 participants | 3 participants | 2 participants | 0 participants | 1 participants | 0 participants |
| Infection by Trichomonas vaginalis No | 4722 participants | 949 participants | 943 participants | 943 participants | 948 participants | 939 participants |
| Infection by Trichomonas vaginalis Yes | 301 participants | 51 participants | 62 participants | 66 participants | 54 participants | 68 participants |
| Injectable contraception use No | 1464 participants | 277 participants | 300 participants | 309 participants | 280 participants | 298 participants |
| Injectable contraception use Yes | 3565 participants | 726 participants | 707 participants | 700 participants | 723 participants | 709 participants |
| Live births | 1.5 children STANDARD_DEVIATION 1.1 | 1.5 children STANDARD_DEVIATION 1.2 | 1.5 children STANDARD_DEVIATION 1.1 | 1.5 children STANDARD_DEVIATION 1.2 | 1.5 children STANDARD_DEVIATION 1.1 | 1.6 children STANDARD_DEVIATION 1.1 |
| Oral pills contraception No | 3889 participants | 788 participants | 769 participants | 771 participants | 780 participants | 781 participants |
| Oral pills contraception Yes | 1140 participants | 215 participants | 238 participants | 238 participants | 223 participants | 226 participants |
| Race/Ethnicity, Customized Bemba | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Black | 322 participants | 64 participants | 65 participants | 65 participants | 64 participants | 64 participants |
| Race/Ethnicity, Customized Chewa | 2 participants | 0 participants | 0 participants | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Chichewa | 30 participants | 2 participants | 7 participants | 7 participants | 10 participants | 4 participants |
| Race/Ethnicity, Customized Colored | 11 participants | 1 participants | 4 participants | 3 participants | 3 participants | 0 participants |
| Race/Ethnicity, Customized Indian | 115 participants | 22 participants | 22 participants | 22 participants | 28 participants | 21 participants |
| Race/Ethnicity, Customized Lombwe | 1 participants | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Lozi | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Ndebele | 106 participants | 22 participants | 25 participants | 18 participants | 27 participants | 14 participants |
| Race/Ethnicity, Customized Other | 120 participants | 25 participants | 24 participants | 30 participants | 24 participants | 17 participants |
| Race/Ethnicity, Customized Other African tribe | 410 participants | 84 participants | 92 participants | 83 participants | 75 participants | 76 participants |
| Race/Ethnicity, Customized Shona | 570 participants | 117 participants | 111 participants | 111 participants | 108 participants | 123 participants |
| Race/Ethnicity, Customized Tonga | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Tumbuka | 3 participants | 1 participants | 0 participants | 1 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized White | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Xhosa | 398 participants | 92 participants | 72 participants | 74 participants | 75 participants | 85 participants |
| Race/Ethnicity, Customized Yao | 2 participants | 1 participants | 0 participants | 0 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Zulu | 2939 participants | 571 participants | 585 participants | 595 participants | 587 participants | 601 participants |
| Region of Enrollment South Africa | 4077 participants | 816 participants | 818 participants | 815 participants | 812 participants | 816 participants |
| Region of Enrollment Uganda | 322 participants | 64 participants | 65 participants | 65 participants | 64 participants | 64 participants |
| Region of Enrollment Zimbabwe | 630 participants | 123 participants | 124 participants | 129 participants | 127 participants | 127 participants |
| Sex: Female, Male Female | 5029 Participants | 1003 Participants | 1007 Participants | 1009 Participants | 1003 Participants | 1007 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Some secondary school education or higher Complete primary school education or lower | 403 participants | 79 participants | 85 participants | 83 participants | 74 participants | 82 participants |
| Some secondary school education or higher Missing | 4 participants | 1 participants | 2 participants | 0 participants | 0 participants | 1 participants |
| Some secondary school education or higher Some secondary school education or higher | 4622 participants | 923 participants | 920 participants | 926 participants | 929 participants | 924 participants |
| Syphilis infection Missing | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants |
| Syphilis infection No | 4960 participants | 992 participants | 993 participants | 993 participants | 988 participants | 994 participants |
| Syphilis infection Yes | 68 participants | 11 participants | 14 participants | 16 participants | 15 participants | 12 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 646 / 1,007 | 740 / 1,003 | 747 / 1,009 | 705 / 1,007 | 715 / 1,003 |
| serious Total, serious adverse events | 17 / 1,007 | 42 / 1,003 | 57 / 1,009 | 39 / 1,007 | 26 / 1,003 |
Outcome results
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
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
Population: All participants randomized (intention-to-treat).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TFV Gel | 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 | 4 participants |
| Placebo Gel | 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 | 13 participants |
| Oral Placebo | 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 | 2 participants |
| TFV Gel | 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 | 9 participants |
| Gel Placebo | 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 | 3 participants |
p-value: 0.004Fisher Exact
Primary
Incidence Rate of HIV-1 Infections of Oral TDF and Oral Placebo Arms
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| TFV Gel | Incidence Rate of HIV-1 Infections of Oral TDF and Oral Placebo Arms | 6.3 cases per 100 person-years |
| Placebo Gel | Incidence Rate of HIV-1 Infections of Oral TDF and Oral Placebo Arms | 4.2 cases per 100 person-years |
Comparison: 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.p-value: 0.0795% CI: [0.97, 2.29]Regression, Cox
Primary
Incidence Rate of HIV-1 Infections of Oral TDF-FTC and Oral Placebo Arms
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| TFV Gel | Incidence Rate of HIV-1 Infections of Oral TDF-FTC and Oral Placebo Arms | 4.7 cases per 100 person-years |
| Placebo Gel | Incidence Rate of HIV-1 Infections of Oral TDF-FTC and Oral Placebo Arms | 4.6 cases per 100 person-years |
Comparison: 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.p-value: 0.8195% CI: [0.73, 1.49]Regression, Cox
Primary
Incidence Rate of HIV-1 Infections of Tenofovir 1% Gel and Vaginal Placebo Gel Arms
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| TFV Gel | Incidence Rate of HIV-1 Infections of Tenofovir 1% Gel and Vaginal Placebo Gel Arms | 6.0 cases per 100 person-years |
| Placebo Gel | Incidence Rate of HIV-1 Infections of Tenofovir 1% Gel and Vaginal Placebo Gel Arms | 6.8 cases per 100 person-years |
Comparison: 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.p-value: 0.3795% CI: [0.61, 1.21]Regression, Cox
Primary
Number of HIV-1 Infections of Oral TDF and Oral Placebo Arms
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| TFV Gel | Number of HIV-1 Infections of Oral TDF and Oral Placebo Arms | 52 participants |
| Placebo Gel | Number of HIV-1 Infections of Oral TDF and Oral Placebo Arms | 35 participants |
Primary
Number of HIV-1 Infections of Oral TDF-FTC and Oral Placebo Arms
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| TFV Gel | Number of HIV-1 Infections of Oral TDF-FTC and Oral Placebo Arms | 61 participants |
| Placebo Gel | Number of HIV-1 Infections of Oral TDF-FTC and Oral Placebo Arms | 60 participants |
Primary
Number of HIV-1 Infections of Tenofovir 1% Gel and Vaginal Placebo Gel Arms
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| TFV Gel | Number of HIV-1 Infections of Tenofovir 1% Gel and Vaginal Placebo Gel Arms | 61 participants |
| Placebo Gel | Number of HIV-1 Infections of Tenofovir 1% Gel and Vaginal Placebo Gel Arms | 70 participants |
Primary
Person-years of Follow-up of Oral TDF and Oral Placebo Arms
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| TFV Gel | Person-years of Follow-up of Oral TDF and Oral Placebo Arms | 823 person-years |
| Placebo Gel | Person-years of Follow-up of Oral TDF and Oral Placebo Arms | 838 person-years |
Primary
Person-years of Follow-up of Oral TDF-FTC and Oral Placebo Arms
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| TFV Gel | Person-years of Follow-up of Oral TDF-FTC and Oral Placebo Arms | 1284 person-years |
| Placebo Gel | Person-years of Follow-up of Oral TDF-FTC and Oral Placebo Arms | 1308 person-years |
Primary
Person-years of Follow-up of Tenofovir 1% Gel and Vaginal Placebo Gel Arms
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| TFV Gel | Person-years of Follow-up of Tenofovir 1% Gel and Vaginal Placebo Gel Arms | 1024 person-years |
| Placebo Gel | Person-years of Follow-up of Tenofovir 1% Gel and Vaginal Placebo Gel Arms | 1030 person-years |
Secondary
Frequency of HIV-1 Drug Resistance in Women Who Acquire HIV-1 Infection While Using Study Product
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TFV Gel | Frequency of HIV-1 Drug Resistance in Women Who Acquire HIV-1 Infection While Using Study Product | M184V mutation | 0 participants |
| TFV Gel | Frequency of HIV-1 Drug Resistance in Women Who Acquire HIV-1 Infection While Using Study Product | No M184V mutation | 58 participants |
| Placebo Gel | Frequency of HIV-1 Drug Resistance in Women Who Acquire HIV-1 Infection While Using Study Product | No M184V mutation | 54 participants |
| Placebo Gel | Frequency of HIV-1 Drug Resistance in Women Who Acquire HIV-1 Infection While Using Study Product | M184V mutation | 1 participants |
| Oral Placebo | Frequency of HIV-1 Drug Resistance in Women Who Acquire HIV-1 Infection While Using Study Product | No M184V mutation | 60 participants |
| Oral Placebo | Frequency of HIV-1 Drug Resistance in Women Who Acquire HIV-1 Infection While Using Study Product | M184V mutation | 0 participants |
| TFV Gel | Frequency of HIV-1 Drug Resistance in Women Who Acquire HIV-1 Infection While Using Study Product | M184V mutation | 0 participants |
| TFV Gel | Frequency of HIV-1 Drug Resistance in Women Who Acquire HIV-1 Infection While Using Study Product | No M184V mutation | 60 participants |
| Gel Placebo | Frequency of HIV-1 Drug Resistance in Women Who Acquire HIV-1 Infection While Using Study Product | M184V mutation | 0 participants |
| Gel Placebo | Frequency of HIV-1 Drug Resistance in Women Who Acquire HIV-1 Infection While Using Study Product | No M184V mutation | 68 participants |