Maternal TDF and FTC to Reduce NNRTI Resistance Mutations After Intrapartum NVP

Study Overview
=================
Brief Summary
-----------------
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).

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.

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

Conditions
-----------------
HIV, Pregnancy

Intervention / Treatment
-----------------
* Drug: Combination tenofovir-emtricitabine


Participation Criteria
=================
Eligibility 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

Ages Eligible for Study
-----------------
Minimum Age: 16 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: combination tenofovir-emtricitabine<br> | Drug: Combination tenofovir-emtricitabine<br>* Tenofovir disoproxil 300 mg / emtricitabine 200 mg taken as a single dose during labor<br>* Other names: Truvada;|
| No Intervention: control arm<br> | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| maternal antiretroviral drug resistance to non-nucloeoside reverse transcriptase inhibitors |  | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| maternal antiretroviral drug resistance to non-nucloeoside reverse transcriptase inhibitors |  | 2 weeks | 
| maternal hematological and renal function after TDF-FTC use |  | 6 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
HIV, Pregnancy, Mother-to-child transmission of HIV, Drug resistance, Nevirapine resistance, NNRTI resistance