CompletedNCT00705679Updated Oct 29, 2021Results posted

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

A Phase 2 interventional study of Emtricitabine/tenofovir disoproxil fumarate and Emtricitabine/tenofovir disoproxil fumarate placebo in HIV Infections, sponsored by National Institute of Allergy and Infectious Diseases (NIAID). Completed at 15 sites in 3 countries. Open to female participants aged 18 Years to 45 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2021-10-29.

Sponsored by National Institute of Allergy and Infectious Diseases (NIAID) · Phase 2, Interventional, and Prevention

Phase: Phase 2
Study type: Interventional
Enrollment: 5,029
Allocation: Randomized
Ages: 18 Years to 45 Years
Sex: Female

Study 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.

Read the 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.

Conditions studied

HIV Infections

Browse trials for

HIV Infections 4,340

Keywords

Microbicide
HIV Seronegativity

In context

HIV Infections

4,340 studies on the registry are indexed under HIV Infections; 240 are open to participants now.

This study's enrollment of 5,029 is above the median of 83 across 3,312 interventional studies indexed under HIV Infections.

Browse HIV Infections studies →

Lead sponsor

National Institute of Allergy and Infectious Diseases (NIAID) is the lead sponsor of 2,445 studies on the registry; 182 are open to participants now.

Of its 402 completed or terminated interventional studies of FDA-regulated products, 300 (75%) have results posted.

Browse National Institute of Allergy and Infectious Diseases (NIAID) studies →

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 45 Years
Sexes eligible: Female
Accepts healthy volunteers: Yes

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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

Study design

Phase: Phase 2
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 5,029 participants (actual)

Study arms

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 · Drug: Tenofovir disoproxil fumarate
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 · Drug: Tenofovir disoproxil fumarate 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 · Drug: Tenofovir disoproxil fumarate placebo
Experimental
4
Application of tenofovir 1% vaginal gel once daily
Drug: Tenofovir 1% vaginal gel
Experimental
5
Application of tenofovir placebo gel once daily
Drug: Tenofovir placebo

Interventions

DrugEmtricitabine/tenofovir disoproxil fumarate
200 mg/300 mg tablet
Also known as: FTC/TDF, Truvada
DrugEmtricitabine/tenofovir disoproxil fumarate placebo
placebo tablet
Also known as: FTC/TDF placebo, Truvada placebo
DrugTenofovir disoproxil fumarate
300 mg tablet
Also known as: TDF
DrugTenofovir disoproxil fumarate placebo
placebo tablet
Also known as: TDF placebo
DrugTenofovir 1% vaginal gel
1 gm/100 ml of 1% gel
Also known as: TFV, 9-[2-(Phosphonomethoxy)propyl]adenine
DrugTenofovir placebo
placebo gel
Also known as: TFV placebo

What researchers measure

Primary outcomes

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
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
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
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
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
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
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
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
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
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

Secondary outcomes

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

Results

Posted Feb 10, 2016

Limitations and caveats

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.

Participant flow

Women were recruited from September 2009 through June 2011 from 15 sites in South Africa, Uganda, and Zimbabwe.

Participant flow — Overall Study
Milestone	Oral TDF	Oral TDF-FTC	Oral Placebo	TFV Gel	Gel Placebo
Started	1007	1003	1009	1007	1003
Completed	942	864	894	927	934
Not completed	65	139	115	80	69
Withdrew: Adverse event	1	1	0	0	0
Withdrew: Death	0	0	3	2	1
Withdrew: Lost to follow-up	32	60	44	30	35
Withdrew: Physician decision	0	1	0	1	0
Withdrew: Withdrawal by subject	32	77	68	47	33

Outcome measures

PrimaryPerson-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
Reported as:: Number · person-years

Person-years of Follow-up of Tenofovir 1% Gel and Vaginal Placebo Gel Arms
person-years	TFV Gel	Placebo Gel
Person-years of Follow-up of Tenofovir 1% Gel and Vaginal Placebo Gel Arms	1024	1030

PrimaryNumber 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
Reported as:: Number · participants

Number of HIV-1 Infections of Tenofovir 1% Gel and Vaginal Placebo Gel Arms
participants	TFV Gel	Placebo Gel
Number of HIV-1 Infections of Tenofovir 1% Gel and Vaginal Placebo Gel Arms	61	70

SecondaryFrequency 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
Reported as:: Number · participants

Frequency of HIV-1 Drug Resistance in Women Who Acquire HIV-1 Infection While Using Study Product
participants	Oral TDF	Oral TDF-FTC	Oral Placebo	TFV Gel	Gel Placebo
M184V mutation	0	1	0	0	0
No M184V mutation	58	54	60	60	68

PrimaryIncidence 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
Reported as:: Number · cases per 100 person-years

Incidence Rate of HIV-1 Infections of Tenofovir 1% Gel and Vaginal Placebo Gel Arms
cases per 100 person-years	TFV Gel	Placebo Gel
Incidence Rate of HIV-1 Infections of Tenofovir 1% Gel and Vaginal Placebo Gel Arms	6.0 (4.6 to 7.6)	6.8 (5.3 to 8.6)

Statistical analysis

TFV Gel vs Placebo Gel · Regression, Cox · p = 0.37 (The two-sided test a priori threshold for statistical significance is 0.05 against an alternative of 0% effectiveness for estimated effectiveness levels between 33.3% and 50.0%.) · Hazard ratio (hr): 0.85 · 95% CI 0.61 to 1.21A ratio less than 1 indicates a lower rate of HIV infection in the active arm compared to the placebo arm. A ratio more than 1 indicates a higher rate of HIV infection in the active arm compared to the placebo arm.

PrimaryPerson-years of Follow-up of Oral TDF and Oral Placebo Arms

Time frame:: For up to 30 months of follow-up
Reported as:: Number · person-years

Person-years of Follow-up of Oral TDF and Oral Placebo Arms
person-years	Oral TDF	Oral Placebo
Person-years of Follow-up of Oral TDF and Oral Placebo Arms	823	838

PrimaryNumber of HIV-1 Infections of Oral TDF and Oral Placebo Arms

Time frame:: For up to 30 months of follow-up
Reported as:: Number · participants

Number of HIV-1 Infections of Oral TDF and Oral Placebo Arms
participants	Oral TDF	Oral Placebo
Number of HIV-1 Infections of Oral TDF and Oral Placebo Arms	52	35

PrimaryIncidence 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
Reported as:: Number · cases per 100 person-years

Incidence Rate of HIV-1 Infections of Oral TDF and Oral Placebo Arms
cases per 100 person-years	Oral TDF	Oral Placebo
Incidence Rate of HIV-1 Infections of Oral TDF and Oral Placebo Arms	6.3 (4.7 to 8.3)	4.2 (2.9 to 5.8)

Statistical analysis

Oral TDF vs Oral Placebo · Regression, Cox · p = 0.07 (The two-sided test a priori threshold for statistical significance is 0.05 against an alternative of 0% effectiveness for estimated effectiveness levels between 33.3% and 50.0%.) · Hazard ratio (hr): 1.49 · 95% CI 0.97 to 2.29A ratio less than 1 indicates a lower rate of HIV infection in the active arm compared to the placebo arm. A ratio more than 1 indicates a higher rate of HIV infection in the active arm compared to the placebo arm.

PrimaryPerson-years of Follow-up of Oral TDF-FTC and Oral Placebo Arms

Time frame:: For up to 30 months of follow-up
Reported as:: Number · person-years

Person-years of Follow-up of Oral TDF-FTC and Oral Placebo Arms
person-years	Oral TDF-FTC	Oral Placebo
Person-years of Follow-up of Oral TDF-FTC and Oral Placebo Arms	1284	1308

PrimaryNumber of HIV-1 Infections of Oral TDF-FTC and Oral Placebo Arms

Time frame:: For up to 30 months of follow-up
Reported as:: Number · participants

Number of HIV-1 Infections of Oral TDF-FTC and Oral Placebo Arms
participants	Oral TDF-FTC	Oral Placebo
Number of HIV-1 Infections of Oral TDF-FTC and Oral Placebo Arms	61	60

PrimaryIncidence 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
Reported as:: Number · cases per 100 person-years

Incidence Rate of HIV-1 Infections of Oral TDF-FTC and Oral Placebo Arms
cases per 100 person-years	Oral TDF-FTC	Oral Placebo
Incidence Rate of HIV-1 Infections of Oral TDF-FTC and Oral Placebo Arms	4.7 (3.6 to 6.1)	4.6 (3.5 to 5.9)

Statistical analysis

Oral TDF-FTC vs Oral Placebo · Regression, Cox · p = 0.81 (The two-sided test a priori threshold for statistical significance is 0.05 against an alternative of 0% effectiveness for estimated effectiveness levels between 33.3% and 50.0%.) · Hazard ratio (hr): 1.04 · 95% CI 0.73 to 1.49A ratio less than 1 indicates a lower rate of HIV infection in the active arm compared to the placebo arm. A ratio more than 1 indicates a higher rate of HIV infection in the active arm compared to the placebo arm.

PrimaryExtended 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
Reported as:: Number · participants

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
participants	Oral TDF	Oral TDF-FTC	Oral Placebo	TFV Gel	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	4	13	2	9	3

Statistical analysis

Oral TDF-FTC vs Oral Placebo · Fisher Exact · p = 0.004Two-sided Fisher's Exact Test.

Adverse events

Collected over each participant followed on study up to 2 years, 6 months. Non-serious events are listed at a 3% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Oral TDF	—	17/1,007 (1.7%)	646/1,007 (64.2%)
Oral TDF-FTC	—	42/1,003 (4.2%)	740/1,003 (73.8%)
Oral Placebo	—	57/1,009 (5.6%)	747/1,009 (74%)
TFV Gel	—	39/1,007 (3.9%)	705/1,007 (70%)
Gel Placebo	—	26/1,003 (2.6%)	715/1,003 (71.3%)

Most frequent serious events

Showing 10 of 102

Most frequent serious events
Event	Oral TDF	Oral TDF-FTC	Oral Placebo	TFV Gel	Gel Placebo
Premature labourPregnancy, puerperium and perinatal conditions	0/1007	2/1003	5/1009	1/1007	1/1003
Haemorrhage in pregnancyPregnancy, puerperium and perinatal conditions	2/1007	4/1003	4/1009	3/1007	2/1003
Post abortion haemorrhagePregnancy, puerperium and perinatal conditions	0/1007	4/1003	2/1009	1/1007	2/1003
HeadacheNervous system disorders	2/1007	2/1003	1/1009	4/1007	1/1003
Pulmonary tuberculosisInfections and infestations	1/1007	1/1003	2/1009	1/1007	3/1003
Congenital anomaly in offspringCongenital, familial and genetic disorders	1/1007	0/1003	0/1009	3/1007	1/1003
GastroenteritisInfections and infestations	0/1007	0/1003	3/1009	0/1007	1/1003
Diabetes mellitusMetabolism and nutrition disorders	0/1007	0/1003	0/1009	0/1007	2/1003
Back painMusculoskeletal and connective tissue disorders	0/1007	0/1003	0/1009	0/1007	2/1003
Suicide attemptPsychiatric disorders	0/1007	2/1003	1/1009	0/1007	0/1003

Most frequent other events

Showing 10 of 21

Most frequent other events
Event	Oral TDF	Oral TDF-FTC	Oral Placebo	TFV Gel	Gel Placebo
ProteinuriaRenal and urinary disorders	154/1007	203/1003	180/1009	165/1007	183/1003
DysuriaRenal and urinary disorders	143/1007	159/1003	176/1009	170/1007	188/1003
HypophosphataemiaMetabolism and nutrition disorders	171/1007	180/1003	184/1009	188/1007	169/1003
Genitourinary chlamydia infectionInfections and infestations	105/1007	144/1003	154/1009	100/1007	107/1003
Vulvovaginal pruritusReproductive system and breast disorders	56/1007	75/1003	80/1009	150/1007	126/1003
Vaginal dischargeReproductive system and breast disorders	100/1007	129/1003	124/1009	119/1007	122/1003
Alanine aminotransferase increasedInvestigations	90/1007	99/1003	116/1009	90/1007	84/1003
Cervical dysplasiaReproductive system and breast disorders	34/1007	100/1003	90/1009	48/1007	49/1003
Aspartate aminotransferase increasedInvestigations	69/1007	87/1003	88/1009	73/1007	58/1003
Vulvovaginitis trichomonalInfections and infestations	62/1007	65/1003	66/1009	46/1007	55/1003

Baseline characteristics

Includes all participants enrolled and randomized to a study arm

Age, Continuous
Age, Continuous(years)	Oral TDF	Oral TDF-FTC	Oral Placebo	TFV Gel	Gel Placebo	Total
Mean	25.5 ± 5.1	25.2 ± 5.2	25.3 ± 5.2	25.3 ± 5.2	25.3 ± 5.1	25.3 ± 5.2

Sex: Female, Male
Sex: Female, Male(Participants)	Oral TDF	Oral TDF-FTC	Oral Placebo	TFV Gel	Gel Placebo	Total
Female	1007	1003	1009	1007	1003	5029
Male	0	0	0	0	0	0

Race/Ethnicity, Customized
Race/Ethnicity, Customized(participants)	Oral TDF	Oral TDF-FTC	Oral Placebo	TFV Gel	Gel Placebo	Total
Chichewa	4	10	7	7	2	30
Lombwe	0	0	0	0	1	1
Yao	1	0	0	0	1	2
Tumbuka	0	1	1	0	1	3
Other African tribe	76	75	83	92	84	410
White	0	0	0	0	0	0
Zulu	601	587	595	585	571	2939
Xhosa	85	75	74	72	92	398
Indian	21	28	22	22	22	115
Colored	0	3	3	4	1	11
Black	64	64	65	65	64	322
Bemba	0	0	0	0	0	0
Chewa	1	1	0	0	0	2
Tonga	0	0	0	0	0	0
Lozi	0	0	0	0	0	0
Shona	123	108	111	111	117	570
Ndebele	14	27	18	25	22	106
Other	17	24	30	24	25	120

Region of Enrollment
Region of Enrollment(participants)	Oral TDF	Oral TDF-FTC	Oral Placebo	TFV Gel	Gel Placebo	Total
South Africa	816	812	815	818	816	4077
Uganda	64	64	65	65	64	322
Zimbabwe	127	127	129	124	123	630

Some secondary school education or higher
Some secondary school education or higher(participants)	Oral TDF	Oral TDF-FTC	Oral Placebo	TFV Gel	Gel Placebo	Total
Some secondary school education or higher	924	929	926	920	923	4622
Complete primary school education or lower	82	74	83	85	79	403
Missing	1	0	0	2	1	4

Earns own income
Earns own income(participants)	Oral TDF	Oral TDF-FTC	Oral Placebo	TFV Gel	Gel Placebo	Total
Yes	569	569	586	587	570	2881
No	438	434	423	420	432	2147
Missing	0	0	0	0	1	1

Live births
Live births(children)	Oral TDF	Oral TDF-FTC	Oral Placebo	TFV Gel	Gel Placebo	Total
Mean	1.6 ± 1.1	1.5 ± 1.1	1.5 ± 1.2	1.5 ± 1.1	1.5 ± 1.2	1.5 ± 1.1

Currently married
Currently married(participants)	Oral TDF	Oral TDF-FTC	Oral Placebo	TFV Gel	Gel Placebo	Total
Yes	207	209	211	210	215	1052
No	800	794	798	797	788	3977

12 further baseline measures are reported on the registry.

Study locations

15 sites

Wits Reproductive Health and HIV Institute CRS (WRHI CRS)
Johannesburg, Gauteng 2001, South Africa
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

References and documents

Publications

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. PubMed 16470118 ↗
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. PubMed 18328009 ↗
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. PubMed 28178109 ↗
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. PubMed 27146827 ↗
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. PubMed 26850270 ↗
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. PubMed 26155597 ↗
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. PubMed 26123563 ↗
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. PubMed 25651245 ↗

Timeline

Tracking since Sep 25, 2026

Not marked actual or estimatedDates not marked actual or estimated

The record gives a start of Aug 2009, a primary completion of Aug 2012 and a completion of Aug 2012. It does not say whether these dates are actual or estimated.

Results were first posted in Feb 2016, 3 years 6 months after primary completion. A results delay was requested in May 2015.

How these figures are worked out, and which studies are left out of them.

Registered: Jun 24, 2008
First posted: Jun 26, 2008
Start: Aug 2009
Primary completionActual: Aug 2012
CompletionActual: Aug 2012
Results delay requested: May 28, 2015
Results first posted: Feb 10, 2016
Last update: Oct 29, 2021

What these dates mean

Start.: When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.: When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.: When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.: Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.

No changes since tracking began. The registry record was last updated on Oct 29, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00705679
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators: Microbicide Trials Network
Responsible party: Sponsor
First posted: Jun 26, 2008
Start date: Aug 2009
Primary completion: Aug 2012
Completion: Aug 2012
Results posted: Feb 10, 2016
Last update: Oct 29, 2021

Study contacts

Zvavahera M. Chirenje, MD, FRCOG

study chair · UZ-UCSF Collaborative Research Programme

Jeanne Marrazzo, MD, MPH

study chair · University of Washington, Division of Allergy and Infectious Disease

View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Feb 2016. You cannot join it, but the record below documents what was studied.

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