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Nucleoside Analogues |
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Clinical Trial: Comparing the Effectiveness of a Triple Nucleoside Reverse Transcriptase Inhibitor Regimen Versus a Protease Inhibitor-Based Regimen In the Prevention of Mother-to-Child Transmission of HIV
This study is not yet open for patient recruitment.
Verified by National Institute of Allergy and Infectious Diseases (NIAID) December 2005
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Purpose
| Condition | Intervention |
|---|---|
| HIV Infections | Drug: Abacavir Drug: Lamivudine and Zidovudine Drug: Lopinavir/Ritonavir Drug: Nevirapine |
MedlinePlus related topics: AIDS
Study Type: Interventional
Study Design: Prevention, Randomized, Double-Blind, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title: A Randomized Trial of Lopinavir/Ritonavir/Combivir Vs. Abacavir/Zidovudine/Lamivudine for Virologic Efficacy and the Prevention of Mother-to-Child HIV Transmission Among Breastfeeding Women With CD4 Counts Greater Than or Equal to 200 Cells/mm3 in Botswana
Secondary Outcomes: Virologic suppression to less that 400 copies/ml at both delivery and during the entire breastfeeding period, regardless of whether or not randomized treatment is being taken at the time of each measurement; virologic suppression to less than 50 copies/ml or 1,000 copies/ml at delivery, during the breastfeeding period, and both at delivery and during the breastfeeding period; HIV-1 RNA levels in plasma and in breast milk at delivery and at 1, 3, and 5 months postpartum; time from randomization to the first adverse event requiring discontinuation of any of the drugs that formed the initial regimen; time from randomization to the first Grade 3 or higher adverse event; occurrence of Grade 3 or higher adverse events by type, grade, body system, and association with study treatment; premature birth and very premature birth, defined as 37 and 32 weeks gestation or less, respectively; low birth weight and very low birth weight, defined as less than 2500 g and less than 1500 g, respectively; growth and developmental delay, defined as standard norms and neurodevelopmental screening; maternal mortality; maternal morbidity, defined as occurrence of Grade 3 or 4 adverse events, hospitalizations, and AIDS-defining or AIDS-associated diagnoses; change in maternal CD4 count from baseline over time to 12 months postpartum; infant mortality; adherence, as measured by questionnaire and pill count; occurrence of HIV-1 RNA genetic mutations associated with viral resistance in maternal plasma and breast milk and infant plasma among transmitting mother-infant pairs at the nearest time to transmission; LPV/RTV concentrations in the serum of 10 pregnant women, after 1 month of LPV/RTV and 3TC/ZDV; antiretroviral concentrations in breast milk and serum and in their infants''''s serum for all transmitting mother-infant pairs and a matched group of non-transmitting pairs
Expected Total Enrollment: 1400
While perinatal HIV infection has become rare in developed countries through the use of highly active antiretroviral therapy (HAART), it remains a serious problem in developing countries. Botswana has a population of approximately 1.7 million; the prevalence of HIV in Botswana is about 37.4%. In the developed world, HAART has revolutionized the prevention of MTCT among nonbreastfed infants. This trial will compare the effectiveness of a protease inhibitor (PI)-based regimen versus a triple nucleoside reverse transcriptase inhibitor (NRTI)-based regimen in preventing MTCT of HIV.
This study will last between 12 and 18 months, depending on when HAART is started and when delivery occurs. Participants will be stratified based on their CD4 count at screening. Women with CD4 counts of 200 cells/mm3 or more will be in one of two treatment groups and will be randomly assigned to receive either TZV twice daily or LPV/RTV and 3TC/ZDV twice daily. Once in labor, treatment group participants will continue to take their assigned HAART regimen and will also be given additional ZDV. Women with CD4 counts less than 200 cells/mm3 will receive nevirapine (NVP) once daily for the first 14 days, then twice daily, and 3TC/ZDV twice daily; these women will be in the observational group.
Shortly after birth, infants will receive single-dose NVP. A 1-month supply of ZDV will be provided to the mother to administer daily to her child. Mothers will stop HAART at 6 months postpartum or when they stop breastfeeding, whichever occurs earlier. A clinical evaluation, blood collection, and HIV prevention counseling will occur at all visits. An obstetrical exam and physical exam will occur at selected visits. There will be 8 study visits for infants. A clinical evaluation will occur at every visit; a physical exam and blood collection will occur at selected visits. Women will provide at least four samples of breast milk during the first 5 months postpartum.
Eligibility
Accepts Healthy Volunteers
Inclusion Criteria for Mothers:
- HIV infected
- Beyond 38th week of pregnancy (treatment group) or 18th week of pregnancy) but not beyond the 34th week of pregnancy (observational group)
- Able to complete study visits until at least 6 months postpartum
- Citizen of Botswana
Exclusion Criteria for Mothers:
- Taken antiretrovirals for more than one week, other than ZDV during a prior pregnancy. Women who have received single-dose NVP in a prior pregnancy are not excluded.
- Certain abnormal laboratory values
- Plan to formula feed
- Known fetal abnormalities that suggest the fetus will not survive to 6 months of gestational age
- Known allergy to any of the study drugs
- Require certain medications
- Previous participation in the "Prevention of Milk-Borne Transmission of HIV-1C in Botswana" (Mashi) study
Location and Contact Information
Roger Shapiro, MD, MPH, Principal Investigator, Division of Infectious Diseases, Beth Israel Deaconess Medical Center
Claire Moffat, MD, MPH, Principal Investigator, Department of Immunology and Infectious Diseases, Harvard School of Public Health
More Information
Click here for more information about abacavir
Click here for more information about lopinavir/ritonavir
Click here for more information about lamivudine/zidovudine
Click here for more information about nevirapine
lick here for more information about HIV and pregnancy
Click here for more information about drug regimens for HIV positive pregnant women
Click here for more information on after birth care for HIV positive women and their babies
Haga clic aquí para más información acerca del VIH y el embarazo
Haga clic aquí para más información acerca de los tratamientos para las mujeres embarazadas infectadas por el VIH
Haga clic aquí para más información acerca del cuidado de las mujeres VIH positivas y sus bebés después del parto
Publications
Cooper ER, Charurat M, Mofenson L, Hanson IC, Pitt J, Diaz C, Hayani K, Handelsman E, Smeriglio V, Hoff R, Blattner W; Women and Infants'''' Transmission Study Group. Combination antiretroviral strategies for the treatment of pregnant HIV-1-infected women and prevention of perinatal HIV-1 transmission. J Acquir Immune Defic Syndr. 2002 Apr 15;29(5):484-94.
Dorenbaum A, Cunningham CK, Gelber RD, Culnane M, Mofenson L, Britto P, Rekacewicz C, Newell ML, Delfraissy JF, Cunningham-Schrader B, Mirochnick M, Sullivan JL; International PACTG 316 Team. Two-dose intrapartum/newborn nevirapine and standard antiretroviral therapy to reduce perinatal HIV transmission: a randomized trial. JAMA. 2002 Jul 10;288(2):189-98.
Moodley D, Moodley J, Coovadia H, Gray G, McIntyre J, Hofmyer J, Nikodem C, Hall D, Gigliotti M, Robinson P, Boshoff L, Sullivan JL; South African Intrapartum Nevirapine Trial (SAINT) Investigators. A multicenter randomized controlled trial of nevirapine versus a combination of zidovudine and lamivudine to reduce intrapartum and early postpartum mother-to-child transmission of human immunodeficiency virus type 1. J Infect Dis. 2003 Mar 1;187(5):725-35. Epub 2003 Feb 24.
Richardson BA, John-Stewart GC, Hughes JP, Nduati R, Mbori-Ngacha D, Overbaugh J, Kreiss JK. Breast-milk infectivity in human immunodeficiency virus type 1-infected mothers. J Infect Dis. 2003 Mar 1;187(5):736-40. Epub 2003 Feb 12.
Rousseau CM, Nduati RW, Richardson BA, Steele MS, John-Stewart GC, Mbori-Ngacha DA, Kreiss JK, Overbaugh J. Longitudinal analysis of human immunodeficiency virus type 1 RNA in breast milk and of its relationship to infant infection and maternal disease. J Infect Dis. 2003 Mar 1;187(5):741-7. Epub 2003 Feb 18.
Last Updated: December 23, 2005
Record first received: December 22, 2005
ClinicalTrials.gov Identifier: NCT00270296
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2006-01-10
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