Safety and Effectiveness of Tenofovir 1% Gel, Tenofovir Disproxil Fumarate, and Emtricitabine/Tenofovir Disoproxil Fumarate Tablets in Preventing HIV in Women

Condition(s) targeted: HIV Infections

Intervention: Emtricitabine/tenofovir disoproxil fumarate (Drug); Emtricitabine/tenofovir disoproxil fumarate placebo (Drug); Tenofovir disoproxil fumarate (Drug); Tenofovir disoproxil fumarate placebo (Drug); Tenofovir 1% vaginal gel (Drug); Tenofovir placebo (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)

Official(s) and/or principal investigator(s):
Zvavahera M. Chirenje, MD, FCROG, Study Chair, Affiliation: UZ-UCSF Collaborative Research Programme
Jeanne Marrazzo, MD, MPH, Study Chair, Affiliation: University of Washington, Division of Allergy and Infectious Disease

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.

Official title: Phase 2B Safety and Effectiveness Study of Tenofovir 1% Gel, Tenofovir Disproxil Fumarate Tablet and Emtricitabine/Tenofovir Disoproxil Fumarate Tablet for the Prevention of HIV Infection in Women

Study design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Primary outcome:

Effectiveness of daily tenofovir 1% gel versus vaginal placebo gel measured by HIV seroconversion

Effectiveness of oral TDF and oral FTC/TDF versus oral placebo measured by HIV seroconversion

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

Secondary outcome:

Adherence to daily regimens of vaginal gel versus oral tablets

Change in sexual activity, condom use, and intravaginal practices over time

Frequency of HIV-1 drug resistance in women who acquire HIV-1 infection while using study product

Reported HIV seroconversion, toxicity, viral resistance, cervicovaginal inflammation, or adverse events

Incidence of HIV seroconversion in each study product group

Relationship between plasma drug concentrations and study outcomes using PK-PD models

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 14 months to a maximum of 35 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. Pharmacokinetic studies will occur at some visits. A pap smear will occur at select visits.

Minimum age: 18 Years. Maximum age: 40 Years. Gender(s): Female.

Criteria:

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 infection 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

College of Med. JHU CRS, Blantyre, Malawi; Not yet recruiting
Leslie Degnan, Phone: 265-888-208609, Email: ldegnan@jhu.medcol.mw

CAPRISA Aurum CRS, Klerksdorp 2571, South Africa; Recruiting
Kathy Mngadi, Phone: 27-18-4064214, Email: kmngadi@auruminstitute.org

Makerere University- JHU Research Collaboration, Kampala, Uganda; Recruiting
Carolyne Onyango, MD, Phone: 256-414-541044, Email: carolonyango@mujhu.org

Seke South CRS, Chitungwiza, Zimbabwe; Recruiting
Margaret Mlingo, Phone: 263-4-2915421, Email: margaret@uz-ucsf.co.zw
Thulani Magwali, MD, Principal Investigator

Zengeza CRS, Chitungwiza, Zimbabwe; Recruiting
Margaret Mlingo, Phone: 263-4-2915421, Email: margaret@uz-ucsf.co.zw

Spilhaus CRS, Harare, Zimbabwe; Recruiting
Margaret Mlingo, Phone: 263-4-2915421, Email: margaret@uz-ucsf.co.zw
Tsitsi Magure, MB ChB, MMED, Principal Investigator

Soweto MTN CRS, Johannesburg, Gauteng, South Africa; Recruiting
Sarita Lalsab, Phone: 27-11-9899781, Email: lalsabs@phru.co.za

RHRU - Research & Training Centre CRS, Johannesburg, Gauteng 2001, South Africa; Recruiting
Godspower Akpomiemie, MPH, Phone: 27-11-3585370, Email: GAkpomiemie@rhru.co.za

Verulam CRS, Durban, KwaZulu-Natal 4390, South Africa; Recruiting
Zakir Gaffoor, Phone: 27-32-5334145, Email: Zakir.gaffoor@mrc.ac.za

R. K. Khan CRS, Durban, KwaZulu-Natal, South Africa; Recruiting
Vijayanand Guddera, PhD, Phone: 27-31-4014150, Email: vguddera@mrc.ac.za

Overport CRS, Durban, KwaZulu-Natal 4091, South Africa; Recruiting
Samantha Sukhdeo, Phone: 27-31-2084535, Email: Samantha.sukhdeo@mrc.ac.za

Botha's Hill CRS, Durban, KwaZulu-Natal 3660, South Africa; Recruiting
Zola Msiska, Phone: 27-31-2423600, Email: zmsiska@mrc.ac.za

Isipingo CRS, Durban, KwaZulu-Natal 4133, South Africa; Recruiting
Nonkululeko Mlotshwa, Phone: 27-31-9027494, Email: nonkululeko.mlotshwa@mrc.ac.za

CAPRISA eThekwini CRS, Durban, KwaZulu-Natal 4011, South Africa; Recruiting
Santhana Gengiah, Phone: 27-031-260 1918, Email: gengiahs@ukzn.ac.za

Umkomaas CRS, Durban, KwaZulu-Natal, South Africa; Recruiting
Brodie Daniels, Phone: 27-31-2423600, Email: bdaniel@mrc.ac.za
Shayhana Ganesh, Principal Investigator

Tongaat CRS, Tongaat, KwaZulu-Natal 4400, South Africa; Recruiting
Jessica Phillip, Phone: 27-31-9027494, Email: Jessica.phillip@mrc.ac.za

Click here for more information about Emtricitabine/tenofovir disoproxil fumarate

Click here for more information on tenofovir

Click here for more information about tenofovir disoproxil fumarate

Click here for the Microbicide Trials Network Web site

Haga clic aquí para ver información sobre este ensayo clínico en español

Related 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.

Rosen RK, Morrow KM, Carballo-Diéguez 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.

Starting date: September 2009
Last updated: August 23, 2010