One Month Dual Antiretroviral Prophylaxis to Prevent Resistance Mutations in Mothers Exposed to Single Dose Nevirapine

Study Overview
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Brief Summary
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The purpose of this study is to determine whether providing zidovudine (ZDV) and didanosine (ddI) during labor and for one month postpartum can reduce the selection of nevirapine (NVP) resistance mutations postpartum in women who received a single dose of nevirapine during labor and standard ZDV prophylaxis for the prevention of mother to child transmission of HIV.

Detailed Description
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A single nevirapine dose to the mother, with or without a dose to the child, in addition to oral ZDV prophylaxis starting from 28 weeks gestation has been proven to be highly effective in reducing further mother-to-child HIV transmission (PMTCT). However, post exposure nevirapine resistance mutations are observed in the mother's viral population. These mutations detectable very early after exposure tend to disappear over time. Nevertheless, they may be associated with decrease in efficacy of non-nucleoside reverse transcriptase inhibitor (NNRTI) containing regimens subsequently given to the women for their own health. Therefore, there is a need for research to prevent selection of resistance in the first place or to overcome the resistance in subsequent treatment of the infected mother or infant. Nevirapine plasma levels above IC50 have been detected in women exposed to a single 200 mg dose of nevirapine in a significant number of women during the third week postpartum. We hypothesize that giving ZDV+ddI to women exposed to nevirapine for one month as soon as possible after exposure may prevent the selection of nevirapine resistance mutations.

Official Title
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A Phase 2, One Arm, Open Label, Feasibility Study Assessing One Month Zidovudine/Didanosine Postpartum Prophylaxis to Prevent Resistance Mutations in Mothers Exposed to Single Dose Nevirapine to Prevent Mother to Child Transmission of HIV

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Zidovudine (ZDV)
* Drug: Didanosine (ddI)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meet all pre-entry criteria; Consent to participate and to be followed for the duration of the study; Present the following laboratory values within 14 days prior to inclusion: Hemoglobin > 8.0 mg/dl Absolute neutrophil count > 1000 cells/mm3 Platelets > 100,000 cells/mm3 Serum creatinine < 1.5 mg/dl (women with a serum creatinine > 1.5 mg/dl must have a measured eight-hour urine creatinine clearance > 70 ml/min) SGPT less than 10 times the upper limit of normal Amylase less than 150/L IU (this upper limit may change slightly depending on the normal range at the hospital laboratory). Exclusion Criteria: Evidence of pre-existing fetal anomalies incompatible with life; Known hypersensitivity to any benzodiazepine or to NVP; Receipt of antiretroviral agent other than ZDV; Receipt of non-allowed concomitant treatment or contraindication to ddI Concurrent participation in another clinical trial; Women with a CD4 count <200/µL or history of oral candidiasis if they are not receiving pneumocystis carinii pneumonia (PCP) prophylaxis Any other contra-indicated drugs during ZDV+ddI treatment for the mother as well as the child (Contra-indicated drugs such as gancyclovir, isoniazid, linezolid, ethambutol, rifabutin, cidofovir are not allowed during the ZDV ddI treatment after delivery in order to prevent pharmacological interactions or overlapping toxicities.)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Zidovudine (ZDV)|Zidovudine 300 mg, twice daily, for one month postpartum. Note: after July 03, 2005, all women received 200 mg, twice daily, for the same duration.|
|Drug: Didanosine (ddI)|250 mg ddI-EC (400 mg if body weight >60 kg) once daily, starting at the onset of labor and for one month postpartum|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with viral NNRTI mutations detectable during the 4 month follow-up compared with the incidence observed in the PHPT-2 clinical trial, who received the same antiretroviral prophylaxis but no post-partum regimen |  | Within 4 months postpartum | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, zidovudine, didanosine, Prevention of mother to child transmission of HIV, nevirapine, Thailand, Resistance, Postpartum period