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

This study has been completed.

Sponsor:

Collaborator:

Harvard School of Public Health

Information provided by (Responsible Party):

National Institute of Allergy and Infectious Diseases (NIAID)

ClinicalTrials.gov Identifier:

NCT00270296

First received: December 22, 2005

Last updated: April 27, 2017

Last verified: April 2017

History of Changes

Purpose

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.

Condition	Intervention	Phase
HIV Infections	Drug: Trizivir Drug: Lamivudine/Zidovudine Drug: Lopinavir/Ritonavir Drug: Nevirapine	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Participant, Care Provider Primary Purpose: Prevention
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

Resource links provided by NLM:

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Zidovudine Lamivudine Lopinavir Trizivir

U.S. FDA Resources

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:

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


Enrollment:	730
Study Start Date:	June 2006
Study Completion Date:	September 2010
Primary Completion Date:	March 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.	Drug: Trizivir 300 mg abacavir sulfate/150 mg lamivudine/300 mg zidovudine tablet taken orally twice daily Other Name: TZV
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.	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
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.	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

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


Ages Eligible for Study:	Child, Adult, Senior
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00270296

Locations


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, Botswana

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Harvard School of Public Health

Investigators


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

More Information

Additional Information:

Click here for more information about abacavir/lamivudine/zidovudine This link exits the ClinicalTrials.gov site

Click here for more information about lopinavir/ritonavir This link exits the ClinicalTrials.gov site

Click here for more information about lamivudine/zidovudine This link exits the ClinicalTrials.gov site

Click here for more information about nevirapine This link exits the ClinicalTrials.gov site

Click here for more information about HIV and pregnancy This link exits the ClinicalTrials.gov site

Click here for more information on medication regimens for HIV positive pregnant women This link exits the ClinicalTrials.gov site

Click here for more information on after birth care for HIV positive women and their babies This link exits the ClinicalTrials.gov site

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Powis KM, Smeaton L, Hughes MD, Tumbare EA, Souda S, Jao J, Wirth KE, Makhema J, Lockman S, Fawzi W, Essex M, Shapiro RL. In-utero triple antiretroviral exposure associated with decreased growth among HIV-exposed uninfected infants in Botswana. AIDS. 2016 Jan;30(2):211-20. doi: 10.1097/QAD.0000000000000895.

Powis K, Lockman S, Smeaton L, Hughes MD, Fawzi W, Ogwu A, Moyo S, van Widenfelt E, von Oettingen J, Makhema J, Essex M, Shapiro RL. Vitamin D insufficiency in HIV-infected pregnant women receiving antiretroviral therapy is not associated with morbidity, mortality or growth impairment in their uninfected infants in Botswana. Pediatr Infect Dis J. 2014 Nov;33(11):1141-7. doi: 10.1097/INF.0000000000000428.

Shapiro RL, Kitch D, Ogwu A, Hughes MD, Lockman S, Powis K, Souda S, Moffat C, Moyo S, McIntosh K, van Widenfelt E, Zwerski S, Mazhani L, Makhema J, Essex M. HIV transmission and 24-month survival in a randomized trial of HAART to prevent MTCT during pregnancy and breastfeeding in Botswana. AIDS. 2013 Jul 31;27(12):1911-20.

Dryden-Peterson S, Jayeoba O, Hughes MD, Jibril H, McIntosh K, Modise TA, Asmelash A, Powis KM, Essex M, Shapiro RL, Lockman S. Cotrimoxazole prophylaxis and risk of severe anemia or severe neutropenia in HAART-exposed, HIV-uninfected infants. PLoS One. 2013 Sep 23;8(9):e74171. doi: 10.1371/journal.pone.0074171. eCollection 2013.

Dryden-Peterson S, Shapiro RL, Hughes MD, Powis K, Ogwu A, Moffat C, Moyo S, Makhema J, Essex M, Lockman S. Increased risk of severe infant anemia after exposure to maternal HAART, Botswana. J Acquir Immune Defic Syndr. 2011 Apr 15;56(5):428-36. doi: 10.1097/QAI.0b013e31820bd2b6.

Powis KM, Smeaton L, Ogwu A, Lockman S, Dryden-Peterson S, van Widenfelt E, Leidner J, Makhema J, Essex M, Shapiro RL. Effects of in utero antiretroviral exposure on longitudinal growth of HIV-exposed uninfected infants in Botswana. J Acquir Immune Defic Syndr. 2011 Feb 1;56(2):131-8. doi: 10.1097/QAI.0b013e3181ffa4f5.

Shapiro RL, Hughes MD, Ogwu A, Kitch D, Lockman S, Moffat C, Makhema J, Moyo S, Thior I, McIntosh K, van Widenfelt E, Leidner J, Powis K, Asmelash A, Tumbare E, Zwerski S, Sharma U, Handelsman E, Mburu K, Jayeoba O, Moko E, Souda S, Lubega E, Akhtar M, Wester C, Tuomola R, Snowden W, Martinez-Tristani M, Mazhani L, Essex M. Antiretroviral regimens in pregnancy and breast-feeding in Botswana. N Engl J Med. 2010 Jun 17;362(24):2282-94. doi: 10.1056/NEJMoa0907736.


Responsible Party:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00270296 History of Changes
Other Study ID Numbers:	BHP 016 U01AI064002 ( US NIH Grant/Contract Award Number )
Study First Received:	December 22, 2005
Results First Received:	March 14, 2017
Last Updated:	April 27, 2017


Studies a U.S. FDA-regulated Drug Product:		Yes

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


Treatment Naive MTCT HIV Seronegativity

Additional relevant MeSH terms:


HIV Infections Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Ritonavir Lopinavir Nevirapine Abacavir Lamivudine Lamivudine, zidovudine drug combination	Zidovudine HIV Protease Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-HIV Agents Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 Enzyme Inhibitors Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors Cytochrome P-450 CYP3A Inducers Cytochrome P-450 Enzyme Inducers

ClinicalTrials.gov processed this record on June 28, 2017

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