A Study of Zidovudine/Lamivudine and Either Nevirapine or Nelfinavir for Reduction of Mother-to-child HIV Transmission During Breastfeeding

NCT00146380 | Completed Phase 2 DMC

• 2 other identifiers: CDC-NCHSTP-3677UR6/CCU018970
• Study Type: interventional
• Target: 520
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to demonstrate that a regimen using highly active antiretroviral therapy (HAART) to maximally suppress maternal viral load in the late antenatal period and during the first six months of lactation is safe, effective and can be implemented in resource poor settings in order to reduce the risk of HIV transmission to the infant.

Conditions

HIV Infections

Keywords

Prevention Mother-to-Child HIV transmission; HIV Seronegativity

Outcome Measures

Primary Outcomes (1)

• 1. To estimate the cumulative risk of infant infection at 6 weeks, 9 months, and 18 months of age among breast fed infants. The anticipated outcome is a transmission rate of <6% at 6 weeks and <8% at 18 months of age.

  6 weeks, 9 months, 18 months

Secondary Outcomes (2)

• 1. To determine infant HIV-free survival rates at 24 months of age.

  24 months

• 2. To evaluate infant and maternal safety, and tolerance of ZDV/3TC and Nevirapine or Nelfinavir given to HIV-infected pregnant women from 34 weeks gestation to 6 months postpartum

  12 months

Interventions

Zidovudine/Lamivudine and either Nevirapine or Nelfinavir DRUG

Zidovudine 300mg po bid from 34 weeks gestation to 6 months postpartum Lamivudine 150mg po bid from 34 weeks gestation to 6 months postpartum AND EITHER Nevirapine 200mg po qd for 2 weeks as lead in then bid from 34 weeks gestation to 6 months postpartum OR Nelfinavir 1250mg po bid from 34 weeks gestation to 6 months postpartum ARVs continued for those that meet WHO treatment criteria

Breastfeeding for 6 months postpartum BEHAVIORAL

Exclusive breastfeeding till five and one half months with rapid weaning over 2 weeks and cessation of breastfeeding at 6 months when ARVs are discontinued

Eligibility Criteria

• Age: 15 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Be a pregnant HIV-infected female presenting prior to 34 weeks gestation who has already chosen to breastfeed after receiving counseling on infant feeding choices according to UNAIDS guidelines which includes counseling and education about the overall benefits of breast feeding as well as the risks of HIV transmission to the infant inherent in breastfeeding.
• Report that they plan to reside in Kisumu for the next 2 years
• Be able to give competent, informed consent if \>18 or have a parent or guardian who can do the same in the case of a minor.
• Be willing to comply with study requirements if they meet study eligibility criteria.
• Meet the following laboratory criteria at enrollment (Efforts will be made to address potentially correctable abnormalities such as anemia, prior to enrollment)
• Documentation of HIV-1 infection according to the Kenyan National PMCT testing algorithm.
• Serum creatinine \<1.5 mg/dl
• Hgb \>7.0 g/dL
• Absolute neutrophil count \> 1000 cells/ml
• Platelet count \>50,000/ml
• SGPT \< 2.5 times upper limit of normal
• Documentation of CD4 count results prior to beginning study drug; which will be used to determine the appropriate HAART regimen -i.e ZDV/3TC/NVP or ZDV/3TC/NLF
• Documentation of Hepatitis B and C infection status (Hepatitis B surface antigen and Hepatitis C antibody)
• Have signed consent and met clinical and laboratory eligibility criteria in order to be enrolled in the trial by 34-36 weeks gestation (preferably at 34 weeks).

You may not qualify if:

• Is participating in other HIV vaccine or antiretroviral trials.
• Has substantial hypersensitivity to any benzodiazepine, including Nevirapine.
• Has history of prior substantial intolerance or severe allergic reaction to Nevirapine, Zidovudine, Lamivudine or Nelfinavir.
• For women who will be placed on NVP, ongoing treatment with rifampin, anticoagulants, benzodiazepines, and magnesium sulfate at time of planned enrollment. For those women who will be placed on NLF, ongoing treatment with amiodarone, quinidine, ergot derivative drugs, rifampin, pimozide, St John's work, lovastatin, simvastatin, midazolam or triazolam
• Has evidence of clinically significant cardiac, respiratory, hepatic, gastrointestinal, endocrine, hematologic, psychiatric, neurologic, or allergic disease that would compromise the ability of the participant to complete the study or the study requirements as determined by the principal investigator or designated associate. The clinical significance of any abnormality is to be evaluated in the context of the safety of the patient volunteer and the objectives of this study.
• Has a history of cytotoxic chemotherapy within one month prior to study entry or current diagnosis of malignancy for which systemic therapy is expected to be required during the period of study.
• Blood pressure \> 160 mm Hg systolic or \> 110 mm Hg diastolic.
• Chronic alcohol or illicit drug use.
• Women who become pregnant again during the study follow-up will NOT be eligible for re-enrollment in the trial if they were enrolled for their previous pregnancy.

Sponsors & Collaborators

• Centers for Disease Control and Prevention: lead

Study Sites (1)

CDC Clincical Research Center

Kisumu, Kenya

Location

Related Publications (3)

• Zeh C, Weidle PJ, Nafisa L, Lwamba HM, Okonji J, Anyango E, Bondo P, Masaba R, Fowler MG, Nkengasong JN, Thigpen MC, Thomas T. HIV-1 drug resistance emergence among breastfeeding infants born to HIV-infected mothers during a single-arm trial of triple-antiretroviral prophylaxis for prevention of mother-to-child transmission: a secondary analysis. PLoS Med. 2011 Mar;8(3):e1000430. doi: 10.1371/journal.pmed.1000430. Epub 2011 Mar 29.

  PMID: 21468304 DERIVED

• Thomas TK, Masaba R, Borkowf CB, Ndivo R, Zeh C, Misore A, Otieno J, Jamieson D, Thigpen MC, Bulterys M, Slutsker L, De Cock KM, Amornkul PN, Greenberg AE, Fowler MG; KiBS Study Team. Triple-antiretroviral prophylaxis to prevent mother-to-child HIV transmission through breastfeeding--the Kisumu Breastfeeding Study, Kenya: a clinical trial. PLoS Med. 2011 Mar;8(3):e1001015. doi: 10.1371/journal.pmed.1001015. Epub 2011 Mar 29.

  PMID: 21468300 DERIVED

• Harris JR, Greene SK, Thomas TK, Ndivo R, Okanda J, Masaba R, Nyangau I, Thigpen MC, Hoekstra RM, Quick RE. Effect of a point-of-use water treatment and safe water storage intervention on diarrhea in infants of HIV-infected mothers. J Infect Dis. 2009 Oct 15;200(8):1186-93. doi: 10.1086/605841.

  PMID: 19758095 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Zidovudine; Lamivudine; Nelfinavir; Lactation; Postpartum Period

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)

Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Dideoxynucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Zalcitabine; Deoxycytidine; Cytidine; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Reproductive Physiological Phenomena; Reproductive and Urinary Physiological Phenomena

Study Officials

• Timothy K Thomas, MD

  Centers for Disease Control and Prevention

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 2, 2005
• First Posted: September 7, 2005
• Study Start: July 1, 2003
• Primary Completion: January 1, 2009
• Study Completion: January 1, 2013
• Last Updated: April 15, 2025

Record last verified: 2025-04

Locations

KE (1)