Maternal TDF and FTC to Reduce NNRTI Resistance Mutations After Intrapartum NVP - Full Text View

Sponsored by:	University of Alabama at Birmingham
Information provided by:	University of Alabama at Birmingham
ClinicalTrials.gov Identifier:	NCT00204308

Purpose

The purpose of this study is to determine whether the addition of tenofovir (TDF) and emtricitabine (FTC)to a standard PMTCT regimen containing single-dose nevirapine (NVP) can reduce the development of post-ingestion HIV resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs).

Condition	Intervention	Phase
HIV Pregnancy	Drug: Single dose maternal tenofovir and emtricitabine	Phase II

MedlinePlus related topics: AIDS AIDS and Pregnancy

Drug Information available for: Zidovudine Nevirapine Tenofovir Tenofovir disoproxil Tenofovir Disoproxil Fumarate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Randomized, Open Label, Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Addition of Single-Dose, Maternal Tenofovir and Emtricitabine to Reduce Non-Nucleoside Reverse Transcriptase Inhibitor Resistance Mutations in the Setting of Zidovudine and Nevirapine for Prevention of Mother-to-Child HIV Transmission

Further study details as provided by University of Alabama at Birmingham:

Primary Outcome Measures:

Frequency of maternal NNRTI resistance mutations at 6 weeks post-ingestion

Secondary Outcome Measures:

Frequency of maternal NNRTI resistance mutations at 2 weeks post-ingestion
Safety of TDF and FTC when used in pregnancy as a single-dose

Estimated Enrollment:	400
Study Start Date:	March 2005
Study Completion Date:	May 2007
Primary Completion Date:	May 2007 (Final data collection date for primary outcome measure)

Detailed Description:

Single-dose intrapartum and neonatal nevirapine (NVP), either alone or in combination with short course zidovudine (ZDV) is in widespread use to prevent mother-to-child HIV transmission throughout the developing world. Though the public health benefits cannot be overstated, widespread use of NVP in this fashion may come at a cost. Non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations are induced in at least 20% and probably a larger proportion of women exposed to NVP in this fashion. Addition of short-course ZDV does not appear to mitigate this effect substantially. The full implications of these NVP resistance mutations are yet unknown, though there is concern that they may result in reduced efficacy of the NVP or other NNRTIs in long-term, therapeutic regimens.

We are conducting a clinical trial of tenofovir (TDF) and emtricitabine (FTC), marketed as a fixed dose combination, Truvada ™, to reduce NNRTI-resistance post-delivery in the setting of NVP with or without ZDV for PMTCT. TDF and FTC are both Category B drugs and are approved for use in pregnancy. They have several characteristics that make them ideal candidate drugs for use in conjunction with NVP, including long intracellular half-lives and established safety profile among adults for HIV treatment.

Women will be enrolled between 28 and 38 weeks of gestation. As part of normal PMTCT services, they may choose NVP-boosted ZDV or single dose NVP for PMTCT; We anticipate that most (~80%) will choose the former. At arrival for delivery, they will be randomized to receive either the two study drugs (intervention) or no drug (control). A total of 400 women will be randomized, and followed, along with their infants, for 6 months.

Eligibility

Ages Eligible for Study:	16 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Serologically confirmed HIV infection;
Gestational age of 28 to 38 weeks;
Previous selection of a NVP-based PMTCT regimen (with or without ZDV)
Willingness to participate in a randomized trial;
Willingness to follow up in a postpartum visit schedule;
Willingness to allow her infant to participate in this trial;

Exclusion Criteria:

Use of antiretroviral medications before this pregnancy, even in a single dose.
Current use of antiretroviral medications for treatment of advanced HIV disease and/or AIDS
Illness or complication of pregnancy likely to warrant transfer to the University Teaching Hospital (UTH), known at time of randomization;
Known or suspected allergy to NVP or other benzodiazepine medications;
History of known liver disease.
Hemoglobin level of 7.9 g/dL or less

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00204308

Locations

Zambia
Kanyama Health Centre
Lusaka, Zambia
Kalingalinga Health Centre
Lusaka, Zambia

Sponsors and Collaborators

University of Alabama at Birmingham

Investigators

Principal Investigator:	Jeffrey S A Stringer, MD	University of Alabama at Birmingham
Study Director:	Benjamin H Chi, MD	University of Alabama at Birmingham

More Information

Publications of Results:

Chi BH, Sinkala M, Mbewe F, Cantrell RA, Kruse G, Chintu N, Aldrovandi GM, Stringer EM, Kankasa C, Safrit JT, Stringer JS. Single-dose tenofovir and emtricitabine for reduction of viral resistance to non-nucleoside reverse transcriptase inhibitor drugs in women given intrapartum nevirapine for perinatal HIV prevention: an open-label randomised trial. Lancet. 2007 Nov 17;370(9600):1698-705. Epub 2007 Nov 7.

Study ID Numbers:	EGSA 19-02
Study First Received:	September 12, 2005
Last Updated:	February 5, 2008
ClinicalTrials.gov Identifier:	NCT00204308
Health Authority:	Zambia: Ministry of Health

Keywords provided by University of Alabama at Birmingham:

HIV
Pregnancy
Mother-to-child transmission of HIV

Drug resistance
Nevirapine resistance
NNRTI resistance

Study placed in the following topic categories:

Nevirapine
Emtricitabine
HIV Infections
Acquired Immunodeficiency Syndrome

Tenofovir
Zidovudine
Tenofovir disoproxil

Additional relevant MeSH terms:

Anti-Infective Agents
Anti-HIV Agents
Anti-Retroviral Agents
Molecular Mechanisms of Pharmacological Action
Therapeutic Uses

Enzyme Inhibitors
Antiviral Agents
Pharmacologic Actions
Nucleic Acid Synthesis Inhibitors
Reverse Transcriptase Inhibitors

ClinicalTrials.gov processed this record on January 16, 2009