Trial of Three Neonatal Antiretroviral Regimens for Prevention of Intrapartum HIV Transmission
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00099359|
Recruitment Status : Completed
First Posted : December 13, 2004
Results First Posted : December 4, 2012
Last Update Posted : December 4, 2012
|Condition or disease||Intervention/treatment||Phase|
|Disease Transmission, Vertical Vertical Human Immunodeficiency Virus Transmission HIV Infections||Drug: Zidovudine Drug: Nevirapine (NVP) Drug: Epivir (3TC) Drug: Nelfinavir (NFV)||Phase 3|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||1735 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase III Randomized Trial of the Safety and Efficacy of Three Neonatal Antiretroviral Regimens for Prevention of Intrapartum HIV-1 Transmission|
|Study Start Date :||February 2004|
|Actual Primary Completion Date :||February 2011|
|Actual Study Completion Date :||February 2011|
Standard of care ( Zidovudine only)
Given for 6 weeks. 12mg PO BID if birthweight (BW) > 2000 grams 8 mg PO BID if BW < 2000 grams
Other Name: Retrovir
Standard of care (Zidovudine) plus Nevirapine
Drug: Nevirapine (NVP)
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
Other Name: Viramune
Standard of Care (Zidovudine) plus 2 weeks of Epivir and Nelfinavir
Drug: Epivir (3TC)
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
Other Name: Lamivudine
Drug: Nelfinavir (NFV)
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
Other Name: Viracept
- Infant HIV Infection Status [ Time Frame: 3 months ]Intrapartum HIV infection at 3 Months
- Participants With Serious Adverse Events [ Time Frame: through age 6 months. ]Serious Adverse Events by System Organ Class=Blood and lymphatic system disorders
- Infant HIV-1 Infection Status [ Time Frame: birth ]In utero HIV-1 infection rate
- Participant Deaths [ Time Frame: through age 6 months ]
- Clinical Covariates of HIV-1 Infection [ Time Frame: through age 3 months ]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 ]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 ]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 ]Descriptive study of NVP pharmacokinetics during first two weeks of life using weight band dosing in a subset of enrolled infants.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00099359
|Study Chair:||Karin Nielsen, MD||University of California, Los Angeles|