The Kisumu Breastfeeding Study

1
The Kisumu Breastfeeding Study

• Timothy Thomas
• GHENT
• 12-12-2002

2
Kisumu Breastfeeding Study (KiBS)

• Sponsored by CDC, KEMRI and Kenyan Ministry of
  Health
• Principal Investigator Timothy Thomas
• Co-Principal Investigators Pauli Amornkul,
  Dorothy Mbori-Ngacha
• Collaborators Kevin De Cock, Larry Slutsker,
  John Vulule, Juliana Otieno, Dan Rosen, Ya Ping
  Shi, Ambrose Misore, John Odondi, Christopher
  Oyoo
• Co-investigators Larry Marum, Anja vant Hoog
• CDC Atlanta Co-Investigators, Medical Officers,
  and Project Coordinator Mary Glenn Fowler
  Denise Jamieson Marc Bulterys April Bell
• Consultants Barbara Marston, Annemieke van Eijk,
  Douglas Taren

3
Why Kisumu?

• Existing infrastructure at CDC field station
• High prevalence of HIV in pregnant women (24-36)
• High rate of MTCT (22)

4
Study Design

• Phase II, open-label, one-arm trial
• Aim To reduce mother-to-child transmission among
  breastfeeding HIV-infected women in a
  resource-limited setting through maximal
  reduction in viral load

5
Study Design - Population

• HIV infected mothers who present to Provincial
  General Hospital and Kisumu District Hospitals
  for Antenatal Care
• Meet eligibility requirements

6
Study Design - Intervention

• Mothers ZDV/3TC NVP from 34 weeks gestation
  through 6 months postpartum
• Infants NVP at birth
• Exclusive breastfeeding with rapid weaning at 6
  months

7
Study Design

• Sample size 480 mother infant pairs (10 loss to
  follow-up)
• Duration 42 - 48 months
• Enrollment 18-24 months
• Follow-up 24 months post-partum

8
Eligibility

• HIV-infected
• Has decided to breastfeed
• 26 - 34 weeks gestation
• 18 or older (or 15 18 with guardian)
• Will remain in Kisumu for the next 2 years
• Meet laboratory screening criteria

9
Primary Objectives

• Estimate cumulative risk of infant infection at 6
  weeks, 9 months and 18 months
• Determine infant HIV-free survival rates at 24
  months
• Evaluate infant and maternal safety, tolerance
  and adherence to regimen

10
Secondary Objectives

• Determine infant survival regardless of HIV
  infection status at 24 months
• Characterize relationship in maternal CD4 and
  viral load to risk of transmission to the infant
• Identify and quantify the rates and types of ARV
  resistant mutations in maternal and infant plasma

11
Secondary Objectives

• Identify and characterize social consequences on
  women taking ARVs in this cultural context
• Assess infant growth during breastfeeding and
  after weaning, stratified by infant HIV infection
  status
• Assess maternal nutritional status
• Assess maternal mortality rates

12
Substudies

• Breast Milk Substudy
• Quantify viral load, emergence and fading of
  resistant mutations and drug levels in blood and
  breast milk among a subsample of women and their
  infants
• Enroll first 150 women who consent to join
  substudy

13
Clinical Trials Research Climate post-HIVNET 012

• This week, the National Institute of Allergy and
  Infectious Diseases (NIAID) discussed with the
  Office of Human Research Protections and the U.S.
  Food and Drug Administration (FDA) preliminary
  findings of reporting and documentation
  deficiencies in a clinical trial examining
  effectiveness of the drug nevirapine in blocking
  transmission of HIV from a mother to her newborn
  baby.
• From NIAID Statement issued March 14, 2002

14
What steps are necessary to conduct a clinical
trial in a resource-limited setting?

• Human subjects requirements (including ethics
  consultation)
• Detailed Manual of Operations (MOO)
• Adverse Event Reporting
• Hiring of staff
• Training
• Informed consent issues
• Study drug accountability
• Site monitoring
• Readiness checklist

15
Human subjects requirements

• Ethics Consultation
• Investigator Responsibilities (according to 45
  CFR 46)
• CDC and KEMRI IRBs

16
Adverse Events Reporting

• Mechanism for reporting serious adverse events
• Adapted DAIDS toxicity tables
• Reporting system with timeline
• Role of SDN
• Safety Review Group

17
Training

• Good Clinical Practice (GCP)
• Good Lab Practice (GLP)
• ARV Training
• MOO Training
• Breastfeeding Intervention Training

18
Informed consent issues

• Key facts summary
• Comprehension assessment
• Translated and back-translated
• Involvement of father
• Witness signature

19
Project Team
20
Questions?
21
Year 2002 Procedures for protection of human
research participants CDC/ATSDR

• Data Monitoring Committees (DMCs formerly Data
  and Safety Monitoring Boards DSMBs)
• CDC conducts relatively few clinical trials,
  compared to NIH or FDA. Still, CDC needs a
  systematic framework to monitor the conduct of
  all CDC-supported or conducted clinical trials to
  ensure the safety of participants and the
  validity and integrity of the data.
• For multisite clinical trials involving
  interventions that entail potential risk to
  participants, a Data Monitoring Committee (DMC)
  should be established. Unfortunately, there is
  presently no consensus on how DMCs should be
  created and operated. Contact Fran Sanden of the
  HSA if you have questions about a DMC.
• CDCs OADS is developing a policy and a
  procedures manual
• for establishing DMCs to monitor CDC studies.