Perinatal Antiretroviral Intensification for PMTCT of HIV in Late Comers

Study Overview
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Brief Summary
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The purpose is to evaluate the efficacy of maternal and infant perinatal antiretroviral prophylaxis intensification for the prevention of mother-to-child intrapartum transmission of HIV-1 in women receiving less than 8 weeks of antiretroviral prophylaxis during pregnancy.

Detailed Description
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Design: a multicenter, phase III, single-arm trial. Perinatal antiretroviral intensification (study treatment) is defined as the addition to the standard of care* for mothers and infants of: Mothers: One NVP 200 mg tablet at onset of labor with continuation of HAART for four weeks postpartum Newborn: AZT+3TC+ NVP for 2 weeks, followed by AZT+3TC for 2 weeks: NVP syrup 2 mg/kg every 24 hours for seven days, followed by NVP syrup 4 mg/kg every 24 hours for seven days. Newborns less than 2500 g will be administered 2mg/kg NVP syrup at each intake AZT syrup 4 mg/ kg will be given every 12 hours for four weeks (preterm infants less than 30 weeks will be administered 2 mg/kg every 12 hours; preterm 30-35 weeks will receive 2 mg/kg every 12 hours for the first 2 weeks, increased to 3 mg/kg for the next 2 weeks). 3TC syrup 2 mg/kg every 12 hours for four weeks. The standard of care in Thailand is defined as: Maternal antiretroviral treatment: ZDV 300 mg, 3TC 150mg and LPV/r 400/100 twice a day starting as soon possible after 14 weeks of pregnancy + ZDV 300 mg every 3 hours during labor; this treatment may be continued, stopped or modified after delivery upon the recommendation of the internist. Newborn: ZDV 4 mg/kg every 12 hours for 4 weeks (ZDV dosing adjusted for premature infants).

Official Title
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PHPT-5 Second Phase: Perinatal Antiretroviral Intensification for the Prevention of Mother-to-child Transmission of HIV in Thai Women Having Received Less Than 8 Weeks of HAART During Pregnancy

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Nevirapine, zidovudine, lamivudine


Participation Criteria
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Eligibility Criteria
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Eligibility. Pregnant women presenting at the prenatal clinics will be eligible if they are confirmed HIV-infected, intend to deliver and bring their infant to a study site for postnatal care for at least 6 months; at least 18 years old; and have given written informed consent to participate in the study, regardless of their CD4 cell count. Maternal inclusion criteria: Evidence of HIV infection, as documented by two serology tests obtained at two different dates; All HIV infected pregnant women will be enrolled, either in the intervention arm or an observational study group. Women more than 30 weeks gestational age at start of antiretroviral treatment will be eligible for the intervention. They will actually receive the study intervention if they present in labor after less than 8 weeks of treatment duration; Women with no ANC will receive standard care and will be enrolled in an observational study group(and their infant will receive standard of care perinatal antiretroviral intensification) Women with less than 30 weeks gestational age at start of treatment will receive standard care and will also be enrolled in the Observational Reference group; Agreement not to breastfeed; Consent to participate and to be followed for the duration of the study Exclusion Criteria: Evidence of pre-existing fetal anomalies incompatible with life; Concurrent participation to any other clinical trial without prior agreement of the two study teams

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Perinatal intensification<br>Perinatal antiretroviral intensification (study treatment): Mothers: One NVP 200 mg tablet at onset of labor with continuation of HAART for four weeks postpartum Newborn: AZT+3TC+ NVP for 2 weeks, followed by AZT+3TC for 2 weeks The standard of care in Thailand is defined as: Maternal: ZDV 300 mg, 3TC 150mg and LPV/r 400/100 twice a day starting as soon possible after 14 weeks of pregnancy + ZDV 300 mg every 3 hours during labor Newborn: ZDV 4 mg/kg every 12 hours for 4 weeks (ZDV dosing adjusted for premature infants). | Drug: Nevirapine, zidovudine, lamivudine<br>* Mothers: One NVP 200 mg tablet at onset of labor with continuation of HAART for four weeks postpartum Newborn: AZT+3TC+ NVP for 2 weeks, followed by AZT+3TC for 2 weeks: NVP syrup 2 mg/kg every 24 hours for seven days, followed by NVP syrup 4 mg/kg every 24 hours for seven days. Newborns less than 2500 g will be administered 2mg/kg NVP syrup at each intake AZT syrup 4 mg/ kg will be given every 12 hours for four weeks (preterm infants less than 30 weeks will be administered 2 mg/kg every 12 hours; preterm 30-35 weeks will receive 2 mg/kg every 12 hours for the first 2 weeks, increased to 3 mg/kg for the next 2 weeks). 3TC syrup 2 mg/kg every 12 hours for four weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of perinatal HIV transmission | HIV DNA PCR analysis at birth, 2 weeks, 1, 2, 4 and 6 months of age | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety for women and neonates | All grade 3 and 4 clinical adverse events and abnormal laboratory values in women will be recorded and graded according to the toxicity tables developed by the DAIDS | Up to 12 Months | 
| Pregnancy outcomes | Evaluation of the rates of live births and stillbirths, as well as birth weight, gestational age at delivery according to the results of the sonogram at first prenatal visit, newborn maturity (Ballard score). | Up to 12 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV-1 infection, Prophylaxis, Mother-to-child transmission HIV-1, Thailand, Developing Countries