Trial of Three Neonatal Antiretroviral Regimens for Prevention of Intrapartum HIV Transmission

• Infant HIV Infection Status [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  Intrapartum HIV infection at 3 Months
  
  
• Participants With Serious Adverse Events [ Time Frame: through age 6 months. ] [ Designated as safety issue: Yes ]
  Serious Adverse Events by System Organ Class=Blood and lymphatic system disorders
  
  

• Infant HIV-1 Infection Status [ Time Frame: birth ] [ Designated as safety issue: No ]
  In utero HIV-1 infection rate
  
  
• Participant Deaths [ Time Frame: through age 6 months ] [ Designated as safety issue: Yes ]
  
• Clinical Covariates of HIV-1 Infection [ Time Frame: through age 3 months ] [ Designated as safety issue: No ]
  Compare HIV-1 RNA levels; CD4+ lymphocyte counts; and rates of genotypic and phenotypic resistance among the three treatment regimens.
  
  
• 3TC and NFV Pharmacokinetics [ Time Frame: through age 14 days ] [ Designated as safety issue: No ]
  Descriptive study of 3TC and NFV pharmacokinetics during first two weeks of life using weight band dosing regimen in a subset of enrolled infants.
  
  
• Risk Factors for Perinatal HIV-1 Transmission [ Time Frame: through age 3 months ] [ Designated as safety issue: No ]
  Risk factors to be assessed include maternal HIV-1 RNA levels at delivery, maternal syphilis and other infections, obstetrical factors such as duration of membrane rupture, and adherence to neonatal medication.
  
  
• NVP Pharmacokinetics [ Time Frame: 14 days ] [ Designated as safety issue: No ]
  Descriptive study of NVP pharmacokinetics during first two weeks of life using weight band dosing in a subset of enrolled infants.
  
  

Despite the notable reductions in perinatal transmission of HIV-1 with antiretroviral therapy and other interventions, perinatal transmission continues to occur at rates of 20-30% among pregnant women who are not identified as HIV-1-infected and/or are not provided with antiretroviral therapy. The optimum treatment strategy for prevention of transmission of HIV-1 to infants born to these women is unknown. No trials have evaluated the efficacy of neonatal antiretroviral therapy alone but observational data suggest benefit from zidovudine (ZDV) therapy given to the infant beginning within 48 hours of birth and continued for six weeks. This protocol will compare the safety and efficacy of three antiretroviral regimens administered in the neonatal period: Arm A- ZDV, Arm B- ZDV plus nevirapine (NVP), and Arm C- ZDV plus nelfinavir (NFV) and lamivudine (3TC). Two regimens were selected based on expected antiretroviral activity, pharmacokinetic data, and toxicity profiles. Standard of care (6 weeks of ZDV) alone will be compared to the 6 weeks of ZDV plus either 3 doses of NVP or 2 weeks of 3TC and NFV. Arm B (ZDV + NVP) is the regimen expected to provide the best profile when factors of efficacy, safety, cost, acceptability and convenience are considered. The comparison of Arms B and C is also of considerable interest since the 2-drug Arm B is easier to implement and less expensive than the triple drug Arm C. Although triple drug therapies have been recommended for post-exposure prophylaxis for needle-stick injuries in high-risk circumstances, it is unknown whether the triple drug arm will provide better efficacy than the 2-drug arm for post-exposure prophylaxis of the infant.

This open-label study is expected to accrue 1731 infants of women identified in labor as being HIV positive or who are HIV positive but have not received antiretroviral medication during the pregnancy. If eligible the infant will be randomized at birth to one of three aforementioned treatment arms. Medical history, social, demographic, physical exam, RNA and T- lymphocyte data are collected on the mother during the delivery visit. The infant will have a birth visit and then return for 1-week, 2-week, 4-week, 3-month and a final 6-month visit. Infant evaluations will include: a medical history and physical exam, DNA testing, CBC and liver function tests, cells for long-term storage and RNA/CD4/CD8 testing if HIV positive. The initial study drug doses will be given to the infant while in the hospital. Mothers will administer the infants' remaining treatment doses at home depending on ability.