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

NCT ID: NCT00705679

Last Updated: 2021-10-29

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

5029 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-08-31

Study Completion Date

2012-08-31

Brief Summary

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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

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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

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HIV Infections

Keywords

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Microbicide HIV Seronegativity

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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1

TDF 300 mg tablet taken orally once daily and one FTC/TDF placebo tablet taken orally once daily for 12 to 36 months

Group Type EXPERIMENTAL

Emtricitabine/tenofovir disoproxil fumarate placebo

Intervention Type DRUG

placebo tablet

Tenofovir disoproxil fumarate

Intervention Type DRUG

300 mg tablet

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

Group Type EXPERIMENTAL

Emtricitabine/tenofovir disoproxil fumarate

Intervention Type DRUG

200 mg/300 mg tablet

Tenofovir disoproxil fumarate placebo

Intervention Type DRUG

placebo tablet

3

TDF placebo tablet taken orally once daily and one FTC/TDF placebo tablet taken orally once daily for 12 to 36 months

Group Type EXPERIMENTAL

Emtricitabine/tenofovir disoproxil fumarate placebo

Intervention Type DRUG

placebo tablet

Tenofovir disoproxil fumarate placebo

Intervention Type DRUG

placebo tablet

4

Application of tenofovir 1% vaginal gel once daily

Group Type EXPERIMENTAL

Tenofovir 1% vaginal gel

Intervention Type DRUG

1 gm/100 ml of 1% gel

5

Application of tenofovir placebo gel once daily

Group Type EXPERIMENTAL

Tenofovir placebo

Intervention Type DRUG

placebo gel

Interventions

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Emtricitabine/tenofovir disoproxil fumarate

200 mg/300 mg tablet

Intervention Type DRUG

Emtricitabine/tenofovir disoproxil fumarate placebo

placebo tablet

Intervention Type DRUG

Tenofovir disoproxil fumarate

300 mg tablet

Intervention Type DRUG

Tenofovir disoproxil fumarate placebo

placebo tablet

Intervention Type DRUG

Tenofovir 1% vaginal gel

1 gm/100 ml of 1% gel

Intervention Type DRUG

Tenofovir placebo

placebo gel

Intervention Type DRUG

Other Intervention Names

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FTC/TDF Truvada FTC/TDF placebo Truvada placebo TDF TDF placebo TFV 9-[2-(Phosphonomethoxy)propyl]adenine TFV placebo

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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Microbicide Trials Network

NETWORK

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Zvavahera M. Chirenje, MD, FRCOG

Role: STUDY_CHAIR

UZ-UCSF Collaborative Research Programme

Jeanne Marrazzo, MD, MPH

Role: STUDY_CHAIR

University of Washington, Division of Allergy and Infectious Disease

Locations

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Wits Reproductive Health and HIV Institute CRS (WRHI CRS)

Johannesburg, Gauteng, South Africa

Site Status

Soweto MTN CRS

Johannesburg, Gauteng, South Africa

Site Status

Overport CRS

Asherville, KwaZulu-Natal, South Africa

Site Status

Chatsworth CRS

Chatsworth, KwaZulu-Natal, South Africa

Site Status

eThekwini CRS

Durban, KwaZulu-Natal, South Africa

Site Status

Umkomaas CRS

eMkhomazi, KwaZulu-Natal, South Africa

Site Status

Tongaat CRS

Tongaat, KwaZulu-Natal, South Africa

Site Status

Verulam CRS

Verulam, KwaZulu-Natal, South Africa

Site Status

Botha's Hill CRS

Westville, KwaZulu-Natal, South Africa

Site Status

Isipingo CRS

Westville, KwaZulu-Natal, South Africa

Site Status

CAPRISA Aurum CRS

Klerksdorp, , South Africa

Site Status

MU-JHU Research Collaboration CRS

Kampala, , Uganda

Site Status

Seke South CRS

Chitungwiza, , Zimbabwe

Site Status

Zengeza CRS

Chitungwiza, , Zimbabwe

Site Status

Spilhaus CRS

Harare, , Zimbabwe

Site Status

Countries

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Malawi South Africa Uganda Zimbabwe

References

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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.

Reference Type BACKGROUND
PMID: 16470118 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18328009 (View on PubMed)

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.

Reference Type DERIVED
PMID: 28178109 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27146827 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26850270 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26155597 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26123563 (View on PubMed)

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.

Reference Type DERIVED
PMID: 25651245 (View on PubMed)

Other Identifiers

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10622

Identifier Type: REGISTRY

Identifier Source: secondary_id

MTN-003

Identifier Type: OTHER

Identifier Source: secondary_id

5U01AI068633-05

Identifier Type: NIH

Identifier Source: secondary_id

View Link

VOICE

Identifier Type: OTHER

Identifier Source: secondary_id

MTN-003 (VOICE)

Identifier Type: -

Identifier Source: org_study_id