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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00270296
Recruitment Status : Completed
First Posted : December 26, 2005
Results First Posted : June 5, 2017
Last Update Posted : June 5, 2017
Sponsor:
Collaborator:
Harvard School of Public Health
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Tracking Information
First Submitted Date  ICMJE December 22, 2005
First Posted Date  ICMJE December 26, 2005
Results First Submitted Date  ICMJE March 14, 2017
Results First Posted Date  ICMJE June 5, 2017
Last Update Posted Date June 5, 2017
Study Start Date  ICMJE June 2006
Actual Primary Completion Date March 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 27, 2017)
  • Number of Participants With Virologic Suppression [ Time Frame: Throughout study, including breastfeeding, assessed up to 24 months ]
    Suppression of the plasma HIV-1 RNA level to less than 400 copies per milliliter
  • Number of HIV+ Infants [ Time Frame: Throughout study, including breastfeeding, assessed up to 24 months ]
    Number of infants with HIV-positive status
Original Primary Outcome Measures  ICMJE
 (submitted: December 22, 2005)
Virologic suppression to less than 400 copies/ml at delivery, regardless of whether or not randomized treatment is being taken at the time or to less than 400 copies/ml during the entire breastfeeding period
Change History Complete list of historical versions of study NCT00270296 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: December 22, 2005)
  • 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 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 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' serum for all transmitting mother-infant pairs and a matched group of non-transmitting pairs
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Trizivir Vs. Kaletra and Combivir for the Prevention of Mother-to-Child Transmission of HIV
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Prevention
Condition  ICMJE HIV Infections
Intervention  ICMJE
  • Drug: Trizivir
    300 mg abacavir sulfate/150 mg lamivudine/300 mg zidovudine tablet taken orally twice daily
    Other Name: TZV
  • Drug: Lamivudine/Zidovudine
    150 mg lamivudine/300 mg zidovudine tablet taken orally twice daily
    Other Names:
    • 3TC/ZDV
    • Combivir
  • Drug: Lopinavir/Ritonavir
    400 mg lopinavir/100 mg ritonavir tablet taken orally twice daily
    Other Name: LPV/RTV
  • Drug: Nevirapine
    200 mg tablet taken orally daily for the first 14 days before receiving 200 mg tablet taken orally twice daily
    Other Name: NVP
Study Arms  ICMJE
  • Experimental: Trizivir (TZV) Arm
    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.
    Intervention: Drug: Trizivir
  • Experimental: Kaletra Arm
    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.
    Interventions:
    • Drug: Lamivudine/Zidovudine
    • Drug: Lopinavir/Ritonavir
  • Experimental: Nevirapine (NVP) Arm
    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.
    Intervention: Drug: Nevirapine
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 24, 2012)
730
Original Enrollment  ICMJE
 (submitted: December 22, 2005)
1400
Actual Study Completion Date  ICMJE September 2010
Actual Primary Completion Date March 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Botswana
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00270296
Other Study ID Numbers  ICMJE BHP 016
U01AI064002 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Institute of Allergy and Infectious Diseases (NIAID)
Study Sponsor  ICMJE National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators  ICMJE Harvard School of Public Health
Investigators  ICMJE
Principal Investigator: Roger Shapiro, MD, MPH Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Botswana-Harvard School of Public Health Partnership for Research and Education
Principal Investigator: Claire Moffat, MD, MPH Department of Immunology and Infectious Diseases, Harvard School of Public Health, Botswana-Harvard School of Public Health Partnership for Research and Education
PRS Account National Institute of Allergy and Infectious Diseases (NIAID)
Verification Date April 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP