Clinical trial NCT00270296: Trizivir Vs. Kaletra and Combivir for the Prevention of Mother-to-Child Transmission of HIV
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Keywords: Treatment Naive
MTCT
HIV Seronegativity
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Harvard School of Public Health (HSPH)
First posted: 2005-12-26
Enrollment: 730
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

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.

Eligibility 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

Primary outcomes:
measure: Number of Participants With Virologic Suppression
timeFrame: Throughout study, including breastfeeding, assessed up to 24 months
measure: Number of HIV+ Infants
timeFrame: Throughout study, including breastfeeding, assessed up to 24 months
Secondary outcomes:
Other outcomes:
Locations:
city: Gaborone
country: Botswana
facility: Princess Marina Hosp., BHP Study Clinic, Gaborone Shapiro CRS
city: Lobatse
country: Botswana
facility: Athlone Hosp., BHP Study Clinic, Lobatse Shapiro CRS
city: Mochudi
country: Botswana
facility: Deborah Reteif Hosp., BHP Study Clinic, Mochudi Shapiro CRS
city: Molepolole
country: Botswana
facility: Scottish Livingstone Hosp., BHP Study Clinic, Molepolole Shapiro CRS
Study officials:
affiliation: Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Botswana-Harvard School of Public Health Partnership for Research and Education
name: Roger Shapiro, MD, MPH
role: 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
name: Claire Moffat, MD, MPH
role: PRINCIPAL_INVESTIGATOR
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