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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Trizivir
* Drug: Lamivudine/Zidovudine
* Drug: Lopinavir/Ritonavir
* Drug: Nevirapine


Participation Criteria
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Eligibility Criteria
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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
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Trizivir (TZV) Arm<br>Participants in the TZV Arm (Arm 1A) will be pregnant women who have CD4 counts of 200 cells/mm3 or more. As the intervention, they will receive TZV twice daily. Once in labor, these participants will continue to take TZV twice daily and will also be given additional ZDV. | Drug: Trizivir<br>* 300 mg abacavir sulfate/150 mg lamivudine/300 mg zidovudine tablet taken orally twice daily<br>* Other names: TZV;|
| Experimental: Kaletra Arm<br>Participants in the Kaletra Arm (Arm 1B) will be pregnant women who have CD4 counts of 200 cells/mm3 or more. As the intervention, they will receive Lamivudine/Zidovudine (3TC/ZDV) and Lopinavir/Ritonavir (LPV/RTV) twice daily. Once in labor, these participants will continue to take TZV twice daily and will also be given additional ZDV. | Drug: Lamivudine/Zidovudine<br>* 150 mg lamivudine/300 mg zidovudine tablet taken orally twice daily<br>* Other names: Combivir;Drug: Lopinavir/Ritonavir<br>* 400 mg lopinavir/100 mg ritonavir tablet taken orally twice daily<br>* Other names: LPV/RTV;|
| Experimental: Nevirapine (NVP) Arm<br>Participants in the NVP Arm (Arm 2) will be pregnant women who have have CD4 counts less than 200 cells/mm3. These participants will receive NVP once daily for the first 14 days, then twice daily, and 3TC/ZDV twice daily; these women will be in the observational group. | Drug: Nevirapine<br>* 200 mg tablet taken orally daily for the first 14 days before receiving 200 mg tablet taken orally twice daily<br>* Other names: NVP;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Number of HIV+ Infants | Number of infants with HIV-positive status | Throughout study, including breastfeeding, assessed up to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Treatment Naive, MTCT, HIV Seronegativity