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

NCT00270296 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: BHP 016U01AI064002
• Study Type: interventional
• Target: 730
• Locations: 1 country
• Sites: 4

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.

Conditions

HIV Infections

Keywords

Treatment Naive; MTCT; HIV Seronegativity

Outcome Measures

Primary Outcomes (2)

• 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

Study Arms (3)

Trizivir (TZV) Arm

EXPERIMENTAL

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

Kaletra Arm

EXPERIMENTAL

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; Drug: Lopinavir/Ritonavir

Nevirapine (NVP) Arm

EXPERIMENTAL

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

Interventions

Trizivir DRUG

300 mg abacavir sulfate/150 mg lamivudine/300 mg zidovudine tablet taken orally twice daily

Also known as: TZV

Trizivir (TZV) Arm

Lamivudine/Zidovudine DRUG

150 mg lamivudine/300 mg zidovudine tablet taken orally twice daily

Also known as: 3TC/ZDV, Combivir

Kaletra Arm

Lopinavir/Ritonavir DRUG

400 mg lopinavir/100 mg ritonavir tablet taken orally twice daily

Also known as: LPV/RTV

Kaletra Arm

Nevirapine DRUG

200 mg tablet taken orally daily for the first 14 days before receiving 200 mg tablet taken orally twice daily

Also known as: NVP

Nevirapine (NVP) Arm

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Harvard School of Public Health (HSPH): collaborator

Study Sites (4)

Princess Marina Hosp., BHP Study Clinic, Gaborone Shapiro CRS

Gaborone, Botswana

Location

Athlone Hosp., BHP Study Clinic, Lobatse Shapiro CRS

Lobatse, Botswana

Location

Deborah Reteif Hosp., BHP Study Clinic, Mochudi Shapiro CRS

Mochudi, Botswana

Location

Scottish Livingstone Hosp., BHP Study Clinic, Molepolole Shapiro CRS

Molepolole, Botswana

Location

Related Publications (13)

• 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. doi: 10.1097/00126334-200204150-00009.

  PMID: 11981365 BACKGROUND

• 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. doi: 10.1001/jama.288.2.189.

  PMID: 12095383 BACKGROUND

• 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.

  PMID: 16369449 BACKGROUND

• 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. doi: 10.1086/367898. Epub 2003 Feb 24.

  PMID: 12599045 BACKGROUND

• 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. doi: 10.1086/374272. Epub 2003 Feb 12.

  PMID: 12599046 BACKGROUND

• 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. doi: 10.1086/374273. Epub 2003 Feb 18.

  PMID: 12599047 BACKGROUND

• 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.

  PMID: 26684818 DERIVED

• 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.

  PMID: 25037041 DERIVED

• 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. doi: 10.1097/qad.0b013e32836158b0.

  PMID: 24180000 DERIVED

• 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.

  PMID: 24086319 DERIVED

• 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.

  PMID: 21266910 DERIVED

• 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.

  PMID: 21124227 DERIVED

• 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.

  PMID: 20554983 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

abacavir, lamivudine, and zidovudine drug combination; lamivudine, zidovudine drug combination; Lopinavir; Nevirapine

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyridines

Results Point of Contact

• Title: Dr. Roger Shapiro
• Organization: Harvard TH Chan School of Public Health

rshapiro@hsph.harvard.edu

617-432-2334

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2005
• First Posted: December 26, 2005
• Study Start: June 1, 2006
• Primary Completion: March 1, 2009
• Study Completion: September 1, 2010
• Last Updated: November 2, 2021
• Results First Posted: June 5, 2017

Record last verified: 2021-10

Locations

BO (4)