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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00270296
• Other study ID #: BHP 016
• Secondary ID: U01AI064002
• Status: Completed
• Phase: Phase 2
• Start date: June 2006
• Est. completion date: September 2010

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 730
• Est. completion date: September 2010
• Est. primary completion date: March 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Trizivir
300 mg abacavir sulfate/150 mg lamivudine/300 mg zidovudine tablet taken orally twice daily
• Lamivudine/Zidovudine
150 mg lamivudine/300 mg zidovudine tablet taken orally twice daily
• Lopinavir/Ritonavir
400 mg lopinavir/100 mg ritonavir tablet taken orally twice daily
• Nevirapine
200 mg tablet taken orally daily for the first 14 days before receiving 200 mg tablet taken orally twice daily

Locations

Country	Name	City	State
Botswana	Princess Marina Hosp., BHP Study Clinic, Gaborone Shapiro CRS	Gaborone
Botswana	Athlone Hosp., BHP Study Clinic, Lobatse Shapiro CRS	Lobatse
Botswana	Deborah Reteif Hosp., BHP Study Clinic, Mochudi Shapiro CRS	Mochudi
Botswana	Scottish Livingstone Hosp., BHP Study Clinic, Molepolole Shapiro CRS	Molepolole

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Harvard School of Public Health (HSPH)

Country where clinical trial is conducted

Botswana, 

References & Publications (6)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Virologic Suppression	Suppression of the plasma HIV-1 RNA level to less than 400 copies per milliliter	Throughout study, including breastfeeding, assessed up to 24 months
Primary	Number of HIV+ Infants	Number of infants with HIV-positive status	Throughout study, including breastfeeding, assessed up to 24 months

External Links

•   Click here for more information about abacavir/lamivudine/zidovudine
•   Click here for more information about HIV and pregnancy
•   Click here for more information about lamivudine/zidovudine
•   Click here for more information about lopinavir/ritonavir
•   Click here for more information about nevirapine
•   Click here for more information on after birth care for HIV positive women and their babies
•   Click here for more information on medication regimens for HIV positive pregnant women