Clinical trial NCT00099359
Conditions: Disease Transmission, Vertical Vertical Human Immunodeficiency Virus Transmission HIV Infections
Keywords: HIV Perinatal Prevention Transmission Nevirapine Epivir Zidovudine Nelfinavir ZDV NVP 3TC NFV Viracept Viramune HIV Seronegativity Treatment Naive
Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Start date: 2004-02-01; Completion date: 2011-02-01
Enrollment: 1735 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Giving anti-HIV medications to babies born of HIV positive mothers right after birth can lower the babies' risk of contracting HIV. This study will assess the safety and efficacy of two different combinations of anti-HIV medications compared to a one drug standard regimen in preventing mother to baby transmission. The one drug standard treatment and two combinations to be studied are: 1) zidovudine, 2) zidovudine/nevirapine and 3) zidovudine/lamivudine/nelfinavir.

Detailed description:
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.

Arms: arm 1: Standard of care ( Zidovudine only) arm 2: Standard of care (Zidovudine) plus Nevirapine arm 3: Standard of Care (Zidovudine) plus 2 weeks of Epivir and Nelfinavir
Interventions: intervention 1: Zidovudine intervention 2: Nevirapine (NVP) intervention 3: Epivir (3TC) intervention 4: Nelfinavir (NFV)
Intervention descriptions: intervention 1: Given for 6 weeks. 12mg PO BID if birthweight (BW) \> 2000 grams 8 mg PO BID if BW \< 2000 grams intervention 2: Standard of Care (Zidovudine) plus

NVP, first dose initiated within 48 hrs of birth, second dose 48 hrs (+ 4 hours) after the first dose, and third dose 96 hours (+ 4 hours) after the second dose :

12 mg PO per dose if BW \> 2000 grams, 8 mg PO per dose if BW \< 2000 grams intervention 3: Stand of care (Zidovudine) plus

3TC, given for 2 weeks: 6 mg po bid if BW \> 2000 grams 4 mg po bid if BW \< 2000 grams AND

NFV, given for 2 weeks:

200 mg po bid if BW \> 3000 grams 150 mg po bid if BW \> 2,000 - 3000 grams 100 mg PO BID if BW \< 2000 grams intervention 4: 200 mg BID if birth weight (BW) \> 3000 grams for 2 weeks;150 mg BID if BW \> 2000-3000 grams for 2 weeks; 100 mg BID BW \</= 2000 grams for 2 weeks

Protocol documents: