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Optimizing Pediatric HIV-1 Treatment, Nairobi, Kenya

This study has been terminated.
(DSMB recommended termination due to high early restart in the interrupted arm)
Sponsor:
Collaborators:
Fred Hutchinson Cancer Research Center
University of Nairobi
Information provided by (Responsible Party):
Grace John, University of Washington
ClinicalTrials.gov Identifier:
NCT00428116
First received: January 22, 2007
Last updated: October 26, 2012
Last verified: October 2012
History of Changes
  Purpose

Given the high mortality associated with infant HIV-1 and the fact that surrogate markers are poorly predictive of mortality risk, some experts recommend empiric highly active antiretroviral therapy (HAART) initiation in infants younger than 12 months. A problem with this approach is that it obligates infants to life-long therapy, which may be associated with cumulative drug toxicity, poor adherence, and treatment failure. Early HAART for prevention of mortality during the first 2 years of life has potential to salvage immune function and alter viral set-point, allowing withdrawal of therapy, perhaps for several years, until subsequent CD4% decline requires it. This untested approach is attractive because it combines the survival benefits of early pediatric HAART therapy with the benefits of antiretroviral deferral.

One hundred and fifty infants who initiated HAART at <13 months of age will be treated with HAART regimen for 24 months after which those who have immune reconstitution and adequate growth (~100) will be randomized to continued versus deferred therapy. Clinical outcomes, growth, and toxicity will be compared in these children to determine if interruption is a safe and beneficial strategy. Follow-up in this studies will be closely monitored by an external Data Safety and Monitoring Board (DSMB).


Condition Intervention Phase
HIV Infections
 Drug: AZT/3TC/NVP (zidovudine/lamivudine/nevirapine)
Drug: d4T/3TC/NVP (stavudine/lamivudine/nevirapine)
Drug: AZT/3TC/ABC (zidovudine/lamivudine/abacavir)
Drug: d4T/3TC/ABC (stavudine/lamivudine/abacavir)
Drug: ddl/ABC/LPV/r (didanosine/abacavir/lopinavir-ritonavir)
Drug: AZT/3TC/ LPV/r (zidovudine/lamivudine/ lopinavir-ritonavir)
Drug: - ABC/ddI or TDF/NVP or EFV (abacavir/didanosine or tenofovir/nevirapine or efavirenz)
Drug: ABC/3TC/NVP (abacavir/lamivudine/nevirapine)
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Optimizing Pediatric HIV-1 Treatment, Nairobi, Kenya (0-4.5 Month RCT)

Resource links provided by NLM:

MedlinePlus related topics: HIV/AIDS
U.S. FDA Resources

Further study details as provided by University of Washington:

Primary Outcome Measures:
  • Growth will be compared in continuous and interrupted therapy arms at every monthly follow-up visits after randomization [ Time Frame: Over 18 months of post-randomization follow-up ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence of morbidities, specifically, pneumonia, diarrhea, and hospitalization. [ Time Frame: Over 24 months of treatment with HAART and 18 months of post-randomization follow-up ] [ Designated as safety issue: No ]

Enrollment: 141
Study Start Date: September 2007
Estimated Study Completion Date: January 2013
Estimated Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Continued HAART
After 24 months of treatment with HAART, half the eligible infants will be randomized to continued treatment with HAART for 18 months.
 Drug: AZT/3TC/NVP (zidovudine/lamivudine/nevirapine)
First line HAART regimen
Drug: d4T/3TC/NVP (stavudine/lamivudine/nevirapine)
First line HAART regimen
Drug: AZT/3TC/ABC (zidovudine/lamivudine/abacavir)
First line HAART regimen
Drug: d4T/3TC/ABC (stavudine/lamivudine/abacavir)
First line HAART regimen
Drug: ddl/ABC/LPV/r (didanosine/abacavir/lopinavir-ritonavir)
Second line HAART regimen
Drug: AZT/3TC/ LPV/r (zidovudine/lamivudine/ lopinavir-ritonavir)
This first line HAART regimen will be provided to infants with prior exposure to nevirapine as part of PMTCT
Drug: - ABC/ddI or TDF/NVP or EFV (abacavir/didanosine or tenofovir/nevirapine or efavirenz)
This is a second line regimen for infants with exposure to nevirapine as part of PMTCT
Drug: ABC/3TC/NVP (abacavir/lamivudine/nevirapine)
First-line regimen
No Intervention: Interrupted HAART
After 24 months of treatment with HAART, half the eligible infants will be randomized to interrupted treatment and followed for 18 months.

Detailed Description:

Hypothesis: Deferring antiretroviral therapy in infants who have immune reconstitution and adequate growth following early therapy of primary infection (initiated HAART during primary infection at less than 13 months of age) will not compromise clinical status or growth and may spare antiretroviral toxicity.

Specific Aim/Primary Objective: To compare growth and morbidity in infants (who initiated HAART during primary infection at less than or equal to 13 months of age with subsequently normalized CD4% and growth following 24 months of HAART) randomized to deferred versus continuous therapy and followed for an additional 18 months.

Secondary Aim/Secondary Objective: To determine predictors of non-progression of HIV among the infants, including: age, adherence, HIV-1 specific immune responses, baseline HIV-1 RNA, CD4 percent and immune activation.

Design: Randomized clinical trial involving HIV-1 treatment of infants (<13 months old) for 24 months, followed by randomization and 18 months follow-up of children randomized to continued versus deferred treatment. This trial is unblinded.

Population: HIV-1 infected infants (<13 months) newly initiating HAART and HIV-1 infected infants already receiving HAART who initiated HAART at age <13 months will be enrolled. After 24 months of treatment follow-up, children with CD4% > 25% and normalized growth will be retained in the study and randomized.

Sample size: 150 infants will be enrolled of which 100 are expected to be eligible for randomization (50 in each arm).

Treatment: All infants will be treated with HAART according to WHO and Kenyan national guidelines. The specific regimens that will be used as a part of this study are:

First line regimen

  • AZT/3TC/NVP (zidovudine/lamivudine/nevirapine)
  • d4T/3TC/NVP (stavudine/lamivudine/nevirapine)
  • AZT/3TC/ABC (zidovudine/lamivudine/abacavir)
  • d4T/3TC/ABC (stavudine/lamivudine/abacavir)
  • ABC/3TC/NVP (abacavir/lamivudine/nevirapine)

Second line regimen

- ddI/ABC/LPV/r (didanosine/abacavir/lopinavir-ritonavir (Kaletra))

For infants with prior exposure to nevirapine as part of PMTCT:

First line regimen - AZT/3TC/LPV/r (zidovudine/lamivudine/lopinavir-ritonavir (kaletra))

Second line regimen

- ABC/ddI or TDF/NVP or EFV (abacavir/didanosine or tenofovir/nevirapine or efavirenz)

  Eligibility

Ages Eligible for Study:   up to 54 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

A. Infants newly initiating HAART

  • Less than 13 months of age
  • HIV-1 DNA detection with confirmation (positive on two HIV-1 DNA filter paper tests)
  • Caregiver of infant plans to reside in Nairobi for at least 3 years (reported by caregiver)
  • Caregiver is able to provide sufficient location information

B. Infants already receiving HAART

  • Initiated HAART at <13 months of age
  • Records confirming HIV positive status
  • Documentation of CD4% and weight prior to HAART initiation
  • Must be on 1st line drug regimen

Eligibility for randomization:

  • Completed 24 months of treatment with HAART
  • Normalized growth: weight for height z-score > -0.5; Child's weight must be above the 5th weight-for-age percentile and the weight curve must not be flat or falling (i.e. cross 2 major percentile lines or more over the past 3 months)
  • CD4% > 25
  • Children who recently initiated or who require anti-tuberculosis treatment at the time of randomization will be ineligible for randomization.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00428116

Sponsors and Collaborators
University of Washington
Fred Hutchinson Cancer Research Center
University of Nairobi
Investigators
Principal Investigator: Dalton Wamalwa, MMed, MPH Department of Paediatrics and Child Health, Kenyatta National Hospital, University of Nairobi
Principal Investigator: Grace C John-Stewart, MD, PhD University of Washington
  More Information

No publications provided

Responsible Party: Grace John, Professor, University of Washington
ClinicalTrials.gov Identifier: NCT00428116     History of Changes
Other Study ID Numbers: 30201-D, 2 RO1 HD023412-16;, 06-1885-D 02
Study First Received: January 22, 2007
Last Updated: October 26, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by University of Washington:
HIV-1
Pediatric
HAART
Treatment Naive

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Didanosine
Zidovudine
Stavudine
Nevirapine
 Lamivudine
Tenofovir
Efavirenz
Abacavir
Ritonavir
Lopinavir
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on May 21, 2013