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

NCT00705679 | Completed Phase 2 Results

• 5 other identifiers: MTN-003 (VOICE)10622MTN-0035U01AI068633-05VOICE
• Study Type: interventional
• Target: 5,029
• Locations: 3 countries
• Sites: 15

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.

Conditions

HIV Infections

Keywords

Microbicide; HIV Seronegativity

Outcome Measures

Primary Outcomes (10)

• 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).

  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

Secondary Outcomes (1)

• Frequency of HIV-1 Drug Resistance in Women Who Acquire HIV-1 Infection While Using Study Product

  Throughout study, up to 2.5 years

Study Arms (5)

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

Drug: Emtricitabine/tenofovir disoproxil fumarate placebo; Drug: Tenofovir disoproxil fumarate

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

Drug: Emtricitabine/tenofovir disoproxil fumarate; Drug: Tenofovir disoproxil fumarate placebo

3

EXPERIMENTAL

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

4

EXPERIMENTAL

Application of tenofovir 1% vaginal gel once daily

Drug: Tenofovir 1% vaginal gel

5

EXPERIMENTAL

Application of tenofovir placebo gel once daily

Drug: Tenofovir placebo

Interventions

Emtricitabine/tenofovir disoproxil fumarate DRUG

200 mg/300 mg tablet

Also known as: FTC/TDF, Truvada

2

Emtricitabine/tenofovir disoproxil fumarate placebo DRUG

placebo tablet

Also known as: FTC/TDF placebo, Truvada placebo

1; 3

Tenofovir disoproxil fumarate DRUG

300 mg tablet

Also known as: TDF

1

Tenofovir disoproxil fumarate placebo DRUG

placebo tablet

Also known as: TDF placebo

2; 3

Tenofovir 1% vaginal gel DRUG

1 gm/100 ml of 1% gel

Also known as: TFV, 9-[2-(Phosphonomethoxy)propyl]adenine

4

Tenofovir placebo DRUG

placebo gel

Also known as: TFV placebo

5

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Microbicide Trials Network: collaborator

Study Sites (15)

Wits Reproductive Health and HIV Institute CRS (WRHI CRS)

Johannesburg, Gauteng, 2001, South Africa

Location

Soweto MTN CRS

Johannesburg, Gauteng, South Africa

Location

Overport CRS

Asherville, KwaZulu-Natal, 4091, South Africa

Location

Chatsworth CRS

Chatsworth, KwaZulu-Natal, 4030, South Africa

Location

eThekwini CRS

Durban, KwaZulu-Natal, 4001, South Africa

Location

Umkomaas CRS

eMkhomazi, KwaZulu-Natal, 4170, South Africa

Location

Tongaat CRS

Tongaat, KwaZulu-Natal, 4400, South Africa

Location

Verulam CRS

Verulam, KwaZulu-Natal, 4340, South Africa

Location

Botha's Hill CRS

Westville, KwaZulu-Natal, 3630, South Africa

Location

Isipingo CRS

Westville, KwaZulu-Natal, 3630, South Africa

Location

CAPRISA Aurum CRS

Klerksdorp, 2571, South Africa

Location

MU-JHU Research Collaboration CRS

Kampala, Uganda

Location

Seke South CRS

Chitungwiza, Zimbabwe

Location

Zengeza CRS

Chitungwiza, Zimbabwe

Location

Spilhaus CRS

Harare, Zimbabwe

Location

Related Publications (8)

• 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.

  PMID: 16470118 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.

  PMID: 18328009 BACKGROUND

• 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.

  PMID: 28178109 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.

  PMID: 27146827 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.

  PMID: 26850270 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.

  PMID: 26155597 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.

  PMID: 26123563 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.

  PMID: 25651245 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Emtricitabine; Tenofovir; Vaginal Creams, Foams, and Jellies; hexadecyloxypropyl 9-(2-(phosphonomethoxy)propyl)adenine

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations; Dosage Forms; Feminine Hygiene Products; Equipment and Supplies

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.

Results Point of Contact

• Title: Jeanne Marrazzo, MD, MPH, FACP, FIDSA
• Organization: University of Washington

jmm2@uw.edu

206-744-3679

Study Officials

• 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

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 24, 2008
• First Posted: June 26, 2008
• Study Start: August 1, 2009
• Primary Completion: August 1, 2012
• Study Completion: August 1, 2012
• Last Updated: October 29, 2021
• Results First Posted: February 10, 2016

Record last verified: 2016-02

Locations

UG (1); ZA (11); ZI (3)