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| ID | Type | Description | Link |
|---|---|---|---|
| 10622 | Registry Identifier | DAIDS ES | |
| MTN-003 | Other Identifier | Microbicide Trials Network | |
| 5U01AI068633-05 | U.S. NIH Grant/Contract | View source | |
| VOICE | Other Identifier | Microbicide Trials Network |
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| Name | Class |
|---|---|
| Microbicide Trials Network | NETWORK |
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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Experimental | TDF 300 mg tablet taken orally once daily and one FTC/TDF placebo tablet taken orally once daily for 12 to 36 months |
|
| 2 | Experimental | 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 |
|
| 3 | Experimental | TDF placebo tablet taken orally once daily and one FTC/TDF placebo tablet taken orally once daily for 12 to 36 months |
|
| 4 | Experimental | Application of tenofovir 1% vaginal gel once daily |
|
| 5 | Experimental | Application of tenofovir placebo gel once daily |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Emtricitabine/tenofovir disoproxil fumarate | Drug | 200 mg/300 mg tablet |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | For up to 30 months of follow-up |
| 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). | For up to 30 months of follow-up |
| 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). | For up to 30 months of follow-up |
| 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. | For up to 30 months of follow-up |
| 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). |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| 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 | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Wits Reproductive Health and HIV Institute CRS (WRHI CRS) | Johannesburg | Gauteng | 2001 | South Africa | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 16470118 | Background | Mayer KH, Maslankowski LA, Gai F, El-Sadr WM, Justman J, Kwiecien A, Masse B, Eshleman SH, Hendrix C, Morrow K, Rooney JF, Soto-Torres L; HPTN 050 Protocol Team. Safety and tolerability of tenofovir vaginal gel in abstinent and sexually active HIV-infected and uninfected women. AIDS. 2006 Feb 28;20(4):543-51. doi: 10.1097/01.aids.0000210608.70762.c3. | |
| 18328009 | Background | Rosen RK, Morrow KM, Carballo-Dieguez A, Mantell JE, Hoffman S, Gai F, Maslankowski L, El-Sadr WM, Mayer KH. Acceptability of tenofovir gel as a vaginal microbicide among women in a phase I trial: a mixed-methods study. J Womens Health (Larchmt). 2008 Apr;17(3):383-92. doi: 10.1089/jwh.2006.0325. |
| Label | URL |
|---|---|
| Click here for the Microbicide Trials Network Web site | View source |
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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.
Women were recruited from September 2009 through June 2011 from 15 sites in South Africa, Uganda, and Zimbabwe.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| FG001 | Oral TDF-FTC |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
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| Emtricitabine/tenofovir disoproxil fumarate placebo | Drug | placebo tablet |
|
|
| Tenofovir disoproxil fumarate | Drug | 300 mg tablet |
|
|
| Tenofovir disoproxil fumarate placebo | Drug | placebo tablet |
|
|
| Tenofovir 1% vaginal gel | Drug | 1 gm/100 ml of 1% gel |
|
|
| Tenofovir placebo | Drug | placebo gel |
|
|
| For up to 30 months of follow-up |
| 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). | For up to 30 months of follow-up |
| 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. | For up to 30 months of follow-up |
| 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). | For up to 30 months of follow-up |
| 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). | For up to 30 months of follow-up |
| 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. | Throughout study, up to 2.5 years |
| Throughout study, up to 2.5 years |
| Soweto MTN CRS |
| Johannesburg |
| Gauteng |
| South Africa |
| Overport CRS | Asherville | KwaZulu-Natal | 4091 | South Africa |
| Chatsworth CRS | Chatsworth | KwaZulu-Natal | 4030 | South Africa |
| eThekwini CRS | Durban | KwaZulu-Natal | 4001 | South Africa |
| Umkomaas CRS | eMkhomazi | KwaZulu-Natal | 4170 | South Africa |
| Tongaat CRS | Tongaat | KwaZulu-Natal | 4400 | South Africa |
| Verulam CRS | Verulam | KwaZulu-Natal | 4340 | South Africa |
| Botha's Hill CRS | Westville | KwaZulu-Natal | 3630 | South Africa |
| Isipingo CRS | Westville | KwaZulu-Natal | 3630 | South Africa |
| CAPRISA Aurum CRS | Klerksdorp | 2571 | South Africa |
| MU-JHU Research Collaboration CRS | Kampala | Uganda |
| Seke South CRS | Chitungwiza | Zimbabwe |
| Zengeza CRS | Chitungwiza | Zimbabwe |
| Spilhaus CRS | Harare | Zimbabwe |
| 28178109 | Derived | Chirenje ZM, Gundacker HM, Richardson B, Rabe L, Gaffoor Z, Nair GL, Mirembe BG, Piper JM, Hillier S, Marrazzo J. Risk Factors for Incidence of Sexually Transmitted Infections Among Women in a Human Immunodeficiency Virus Chemoprevention Trial: VOICE (MTN-003). Sex Transm Dis. 2017 Mar;44(3):135-140. doi: 10.1097/OLQ.0000000000000568. |
| 27146827 | Derived | Moodley J, Naidoo S, Moodley J, Ramjee G. Sharing of Investigational Drug Among Participants in the Voice Trial. AIDS Behav. 2016 Nov;20(11):2709-2714. doi: 10.1007/s10461-016-1414-x. |
| 26850270 | Derived | van der Straten A, Brown ER, Marrazzo JM, Chirenje MZ, Liu K, Gomez K, Marzinke MA, Piper JM, Hendrix CW; MTN-003 VOICE Protocol Team for Microbicide Trials Network. Divergent adherence estimates with pharmacokinetic and behavioural measures in the MTN-003 (VOICE) study. J Int AIDS Soc. 2016 Feb 4;19(1):20642. doi: 10.7448/IAS.19.1.20642. eCollection 2016. |
| 26155597 | Derived | Noguchi LM, Richardson BA, Baeten JM, Hillier SL, Balkus JE, Chirenje ZM, Bunge K, Ramjee G, Nair G, Palanee-Phillips T, Selepe P, van der Straten A, Parikh UM, Gomez K, Piper JM, Watts DH, Marrazzo JM; VOICE Study Team. Risk of HIV-1 acquisition among women who use diff erent types of injectable progestin contraception in South Africa: a prospective cohort study. Lancet HIV. 2015 Jul;2(7):e279-87. doi: 10.1016/S2352-3018(15)00058-2. |
| 26123563 | Derived | Dai JY, Hendrix CW, Richardson BA, Kelly C, Marzinke M, Chirenje ZM, Marrazzo JM, Brown ER. Pharmacological Measures of Treatment Adherence and Risk of HIV Infection in the VOICE Study. J Infect Dis. 2016 Feb 1;213(3):335-42. doi: 10.1093/infdis/jiv333. Epub 2015 Jun 29. |
| 25651245 | Derived | Marrazzo JM, Ramjee G, Richardson BA, Gomez K, Mgodi N, Nair G, Palanee T, Nakabiito C, van der Straten A, Noguchi L, Hendrix CW, Dai JY, Ganesh S, Mkhize B, Taljaard M, Parikh UM, Piper J, Masse B, Grossman C, Rooney J, Schwartz JL, Watts H, Marzinke MA, Hillier SL, McGowan IM, Chirenje ZM; VOICE Study Team. Tenofovir-based preexposure prophylaxis for HIV infection among African women. N Engl J Med. 2015 Feb 5;372(6):509-18. doi: 10.1056/NEJMoa1402269. |
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 |
| FG002 | 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 |
| FG003 | TFV Gel | Application of tenofovir 1% vaginal gel once daily Tenofovir 1% vaginal gel: 1 gm/100 ml of 1% gel |
| FG004 | Gel Placebo | Application of tenofovir placebo gel once daily Tenofovir placebo: placebo gel |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Includes all participants enrolled and randomized to a study arm
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| BG001 | 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 |
| BG002 | 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 |
| BG003 | TFV Gel | Application of tenofovir 1% vaginal gel once daily Tenofovir 1% vaginal gel: 1 gm/100 ml of 1% gel |
| BG004 | Gel Placebo | Application of tenofovir placebo gel once daily Tenofovir placebo: placebo gel |
| BG005 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | Response to the question: What is your ethnic group or tribe? | Number | participants |
| |||||||||||||||
| Region of Enrollment | Country at time of enrollment | Number | participants |
| |||||||||||||||
| Some secondary school education or higher | Response to question: What is your highest level of education? | Number | participants |
| |||||||||||||||
| Earns own income | Response to question: Do you earn an income of your own? | Number | participants |
| |||||||||||||||
| Live births | Response to question: How many children have you given birth to who were alive at birth? | Mean | Standard Deviation | children |
| ||||||||||||||
| Currently married | Response to question: Are you currently married? | Number | participants |
| |||||||||||||||
| At least 2 male sex partners in the past 3 months | Includes primary partner and at least 1 other male partner with which the participant has had vaginal sex in the past 3 months | Number | participants |
| |||||||||||||||
| Episodes of vaginal intercourse in the past 7 days | Mean | Standard Deviation | episodes |
| |||||||||||||||
| Condom use during last vaginal intercourse | Number | participants |
| ||||||||||||||||
| Anal sex in the previous 3 months | A response of 1 or more to the question: In the past 3 months how many times have you had anal sex? | Number | participants |
| |||||||||||||||
| Injectable contraception use | Response to question: What method(s) of contraception/family planning is the participant currently using? (Participant could indicate more than one method.) | Number | participants |
| |||||||||||||||
| Oral pills contraception | Response to question: What method(s) of contraception/family planning is the participant currently using? (Participant could indicate more than one method.) | Number | participants |
| |||||||||||||||
| Infection by Chlamydia trachomatis | Testing was performed with the use of a strand-displacement amplification assay | Number | participants |
| |||||||||||||||
| Infection by Neisseria gonorrhoeae | Testing was performed with the use of a strand-displacement amplification assay | Number | participants |
| |||||||||||||||
| Infection by Trichomonas vaginalis | Testing was performed with the use of the OSOM Trichomonas Rapid Test | Number | participants |
| |||||||||||||||
| Syphilis infection | Testing was performed with the use of a rapid plasma reagin screening test followed by a confirmatory microhemagglutinin assay | Number | participants |
| |||||||||||||||
| HSV-2 infection | 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. | Number | participants |
| |||||||||||||||
| Bacterial vaginosis infection | Bacterial vaginosis was determined by the Nugent score on Gram's staining of vaginal fluid (Nugent score 7-10). | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | Number | person-years | For up to 30 months of follow-up |
|
|
| |||||||||||||||||||||||||||||
| 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). | 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. | Posted | Number | participants | For up to 30 months of follow-up |
|
| ||||||||||||||||||||||||||||||
| 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. | 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. | Posted | Number | participants | Throughout study, up to 2.5 years |
| |||||||||||||||||||||||||||||||
| 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). | 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. | Posted | Number | 95% Confidence Interval | cases per 100 person-years | For up to 30 months of follow-up |
|
| |||||||||||||||||||||||||||||
| 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. | 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. | Posted | Number | person-years | For up to 30 months of follow-up |
| |||||||||||||||||||||||||||||||
| 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). | 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. | Posted | Number | participants | For up to 30 months of follow-up |
|
| ||||||||||||||||||||||||||||||
| 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). | 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. | Posted | Number | 95% Confidence Interval | cases per 100 person-years | For up to 30 months of follow-up |
|
| |||||||||||||||||||||||||||||
| 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. | 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. | Posted | Number | person-years | For up to 30 months of follow-up |
| |||||||||||||||||||||||||||||||
| 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). | 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. | Posted | Number | participants | For up to 30 months of follow-up |
|
| ||||||||||||||||||||||||||||||
| 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). | 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. | Posted | Number | 95% Confidence Interval | cases per 100 person-years | For up to 30 months of follow-up |
|
| |||||||||||||||||||||||||||||
| 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. | All participants randomized (intention-to-treat). | Posted | Number | participants | Throughout study, up to 2.5 years |
|
each participant followed on study up to 2 years, 6 months
Participants systematically reported any adverse experiences at monthly follow-up visits.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 | 17 | 1,007 | 646 | 1,007 | ||
| EG001 | 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 | 42 | 1,003 | 740 | 1,003 | ||
| EG002 | 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 | 57 | 1,009 | 747 | 1,009 | ||
| EG003 | TFV Gel | Application of tenofovir 1% vaginal gel once daily Tenofovir 1% vaginal gel: 1 gm/100 ml of 1% gel | 39 | 1,007 | 705 | 1,007 | ||
| EG004 | Gel Placebo | Application of tenofovir placebo gel once daily Tenofovir placebo: placebo gel | 26 | 1,003 | 715 | 1,003 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lymph node pain | Blood and lymphatic system disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Congenital anomaly in offspring | Congenital, familial and genetic disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Keratoconus | Eye disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Retinal detachment | Eye disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Food poisoning | Gastrointestinal disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Gastric ulcer | Gastrointestinal disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Umbilical hernia | Gastrointestinal disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Death | General disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Suprapubic pain | General disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Cholecystitis | Hepatobiliary disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Drug-induced liver injury | Hepatobiliary disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Abdominal wall abscess | Infections and infestations | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Appendicitis | Infections and infestations | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Bartholin's abscess | Infections and infestations | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Breast abscess | Infections and infestations | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Disseminated tuberculosis | Infections and infestations | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Gingival abscess | Infections and infestations | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Malaria | Infections and infestations | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Meningitis | Infections and infestations | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Meningitis bacterial | Infections and infestations | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Meningitis viral | Infections and infestations | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Pelvic inflammatory disease | Infections and infestations | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Pericarditis tuberculous | Infections and infestations | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Postoperative wound infection | Infections and infestations | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Pulmonary tuberculosis | Infections and infestations | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Pyelonephritis | Infections and infestations | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Skin infection | Infections and infestations | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Tonsillitis | Infections and infestations | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Tuberculosis | Infections and infestations | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Vulval abscess | Infections and infestations | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Wound sepsis | Infections and infestations | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Abdominal injury | Injury, poisoning and procedural complications | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Ankle fracture | Injury, poisoning and procedural complications | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Electric shock | Injury, poisoning and procedural complications | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Foreign body | Injury, poisoning and procedural complications | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Injury | Injury, poisoning and procedural complications | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Internal injury | Injury, poisoning and procedural complications | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Joint dislocation | Injury, poisoning and procedural complications | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Laceration | Injury, poisoning and procedural complications | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Lower limb fracture | Injury, poisoning and procedural complications | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Overdose | Injury, poisoning and procedural complications | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Pelvic fracture | Injury, poisoning and procedural complications | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Stab wound | Injury, poisoning and procedural complications | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Tendon injury | Injury, poisoning and procedural complications | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Thermal burn | Injury, poisoning and procedural complications | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Upper limb fracture | Injury, poisoning and procedural complications | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Diabetes mellitus | Metabolism and nutrition disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Rheumatoid arthritis | Musculoskeletal and connective tissue disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Gliomatosis cerebri | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Lipoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Uterine leiomyoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Cerebral infarction | Nervous system disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Epilepsy | Nervous system disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Loss of consciousness | Nervous system disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Meningism | Nervous system disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Migraine | Nervous system disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Optic neuritis | Nervous system disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Transient ischaemic attack | Nervous system disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Abortion threatened | Pregnancy, puerperium and perinatal conditions | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Ectopic pregnancy | Pregnancy, puerperium and perinatal conditions | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Haemorrhage in pregnancy | Pregnancy, puerperium and perinatal conditions | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Hyperemesis gravidarum | Pregnancy, puerperium and perinatal conditions | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Intrapartum haemorrhage | Pregnancy, puerperium and perinatal conditions | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Post abortion haemorrhage | Pregnancy, puerperium and perinatal conditions | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Pre-eclampsia | Pregnancy, puerperium and perinatal conditions | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Premature labour | Pregnancy, puerperium and perinatal conditions | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Premature rupture of membranes | Pregnancy, puerperium and perinatal conditions | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Retained products of conception | Pregnancy, puerperium and perinatal conditions | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Bipolar disorder | Psychiatric disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Depression suicidal | Psychiatric disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Intentional self-injury | Psychiatric disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Suicidal ideation | Psychiatric disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Suicide attempt | Psychiatric disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Urinary tract obstruction | Renal and urinary disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Bartholin's cyst | Reproductive system and breast disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Breast discharge | Reproductive system and breast disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Breast enlargement | Reproductive system and breast disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Menorrhagia | Reproductive system and breast disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Metrorrhagia | Reproductive system and breast disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Pelvic pain | Reproductive system and breast disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (12.1-16.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Genitourinary chlamydia infection | Infections and infestations | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Genitourinary tract gonococcal infection | Infections and infestations | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Vaginitis bacterial | Infections and infestations | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Vulvovaginal candidiasis | Infections and infestations | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Vulvovaginitis trichomonal | Infections and infestations | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Blood phosphorus decreased | Investigations | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Haemoglobin decreased | Investigations | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Dysuria | Renal and urinary disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Pollakiuria | Renal and urinary disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Proteinuria | Renal and urinary disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Cervical dysplasia | Reproductive system and breast disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Menorrhagia | Reproductive system and breast disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Metrorrhagia | Reproductive system and breast disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Pelvic pain | Reproductive system and breast disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Vaginal discharge | Reproductive system and breast disorders | MedDRA (12.1-16.0) | Systematic Assessment |
| |
| Vulvovaginal pruritus | Reproductive system and breast disorders | MedDRA (12.1-16.0) | Systematic Assessment |
|
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.
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jeanne Marrazzo, MD, MPH, FACP, FIDSA | University of Washington | 206-744-3679 | jmm2@uw.edu |
| ID | Term |
|---|---|
| D015658 | HIV Infections |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000069480 | Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination |
| D000068679 | Emtricitabine |
| D000068698 | Tenofovir |
| D014622 | Vaginal Creams, Foams, and Jellies |
| C524480 | hexadecyloxypropyl 9-(2-(phosphonomethoxy)propyl)adenine |
| ID | Term |
|---|---|
| D063065 | Organophosphonates |
| D009943 | Organophosphorus Compounds |
| D009930 | Organic Chemicals |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D000225 | Adenine |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D003853 | Deoxyribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D004338 | Drug Combinations |
| D004364 | Pharmaceutical Preparations |
| D004304 | Dosage Forms |
| D053566 | Feminine Hygiene Products |
| D004864 | Equipment and Supplies |
Not provided
Not provided
| Male |
|
| Lombwe |
|
| Yao |
|
| Tumbuka |
|
| Other African tribe |
|
| White |
|
| Zulu |
|
| Xhosa |
|
| Indian |
|
| Colored |
|
| Black |
|
| Bemba |
|
| Chewa |
|
| Tonga |
|
| Lozi |
|
| Shona |
|
| Ndebele |
|
| Other |
|
| Uganda |
|
| Zimbabwe |
|
| Complete primary school education or lower |
|
| Missing |
|
| No |
|
| Missing |
|
| No |
|
| No |
|
| No response |
|
| No |
|
| Missing |
|
| No |
|
| Missing |
|
| No |
|
| No |
|
| No |
|
| Missing |
|
| No |
|
| Missing |
|
| No |
|
| Missing |
|
| No |
|
| Missing |
|
| No |
|
| Missing |
|
| No |
|
| Missing |
|
|
| OG002 | 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 |
| OG003 | TFV Gel | Application of tenofovir 1% vaginal gel once daily Tenofovir 1% vaginal gel: 1 gm/100 ml of 1% gel |
| OG004 | Gel Placebo | Application of tenofovir placebo gel once daily Tenofovir placebo: placebo gel |
|
|
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
|
|
|
|
|
| Units |
|---|
| Counts |
|---|
| Participants |
|
|
| Participants |
|
|
|
|
|
| OG003 | TFV Gel | Application of tenofovir 1% vaginal gel once daily Tenofovir 1% vaginal gel: 1 gm/100 ml of 1% gel |
| OG004 | Gel Placebo | Application of tenofovir placebo gel once daily Tenofovir placebo: placebo gel |
|
|
|