Trizivir Vs. Kaletra and Combivir for the Prevention of Mother-to-Child Transmission of HIV

Condition(s) targeted: HIV Infections

Intervention: Trizivir (Drug); Lamivudine/Zidovudine (Drug); Lopinavir/Ritonavir (Drug); Nevirapine (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)

Official(s) and/or principal investigator(s):
Roger Shapiro, MD, MPH, Principal Investigator, Affiliation: Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Botswana-Harvard School of Public Health Partnership for Research and Education
Claire Moffat, MD, MPH, Principal Investigator, Affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Botswana-Harvard School of Public Health Partnership for Research and Education

Overall contact:
Claire Moffat, MD, MPH, Phone: 267-390-2671, Email: cmoffat@bhp.org.bw

Anti-HIV drug regimens have dramatically improved the rates of prevention of mother-to-child transmission (MTCT) of HIV in developed countries. However, little is known of the effectiveness of such regimens in developing countries, such as Botswana. This study will determine whether Trizivir (TZV), a single pill containing abacavir sulfate, lamivudine, and zidovudine (ABC/3TC/ZDV), or lopinavir/ritonavir (LPV/r) and lamivudine/zidovudine (3TC/ZDV) is more effective in reducing HIV-1 viral load and preventing MTCT among HIV infected pregnant women in Botswana.

Official title: 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

Study design: Prevention, Randomized, Double Blind (Subject, Caregiver), Active Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome:

Virologic suppression

Infant's HIV status

Secondary outcome:

HIV-1 RNA levels in plasma and breast milk

HIV-1 DNA levels in breast milk

Time from randomization to the first adverse event requiring discontinuation of any of the drugs that formed the initial regimen by treatment arm and compared to Mashi study

Time from randomization to the first Grade 3 or higher adverse event by treatment arm and compared to Mashi study

Occurrence of Grade 3 or higher adverse events by type, grade, body system, and association with study treatment compared to Mashi study

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 2,500 g and less than 1,500 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

Infant mortality

Comparison of neurodevelopment at 2 years of age in the Mashi study and this study

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

Antiretroviral therapy (ARV) toxicities and viral load differences by maternal HLA type, for subset of up to 500 women with HLA-type available

ARV concentrations in breast milk and serum and in their infants' serum for all transmitting mother-infant pairs and a matched group of nontransmitting pairs

Detailed description: 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 up to 24 months for mothers and their children. 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 maternal visits. An obstetrical exam and physical exam will occur at selected visits. Women will provide at least four samples of breast milk during the first 5 months postpartum. For infants, a clinical evaluation will occur at every visit, and a physical exam and blood collection will occur at selected visits.

Minimum age: N/A. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria for Mothers:

- HIV-infected

- At least at 26th week of pregnancy (treatment group) or 18th week of pregnancy

(observational group) but not beyond the 34th week of pregnancy

- Able to complete study visits until at least 6 months postpartum

- Citizen of Botswana

Exclusion Criteria for Mothers:

- Taken ARVs for more than 1 week, other than ZDV, during current or 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 or medical contraindication 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

- Currently incarcerated

Claire Moffat, MD, MPH, Phone: 267-390-2671, Email: cmoffat@bhp.org.bw

Princess Marina Hospital, Gabarone, Botswana; Recruiting

Scottish Livingstone Hospital, Molepolole, Botswana; Recruiting

Athelone Hospital, Lobatse, Botswana; Recruiting

Deborah Retief Hospital, Mochudi, Botswana; Recruiting

Click here for more information about abacavir/lamivudine/zidovudine

Click here for more information about lopinavir/ritonavir

Click here for more information about lamivudine/zidovudine

Click here for more information about nevirapine

Click here for more information about HIV and pregnancy

Click here for more information on medication regimens for HIV positive pregnant women

Click here for more information on after birth care for HIV positive women and their babies

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Related 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.

Jones BM, Chiu SS, Wong WH, Lim WW, Lau YL. Cytokine profiles in human immunodeficiency virus-infected children treated with highly active antiretroviral therapy. MedGenMed. 2005 May 3;7(2):71.

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.

Starting date: June 2006
Ending date: May 2011
Last updated: August 28, 2008