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-Stewart, University of Washington
ClinicalTrials.gov Identifier:
NCT00428116
First received: January 22, 2007
Last updated: February 11, 2014
Last verified: February 2014

January 22, 2007
February 11, 2014
September 2007
July 2013   (final data collection date for primary outcome measure)
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 ]
  • WHO stage of AIDS will be compared in continuous and interrupted therapy arms at every monthly follow-up visits after randomization
  • Weight-for-height z-scores will be compared in continuous and interrupted therapy arms at every monthly follow-up visits after randomization
  • Immunologic status (CD4%) will be compared in continuous and interrupted therapy arms at every 3-monthly follow-up visits after randomization
Complete list of historical versions of study NCT00428116 on ClinicalTrials.gov Archive Site
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 ]
  • Predictors of non-progression of HIV among infants:
  • Age at initiation of HAART
  • Adherence to HAART
  • HIV-1 specific immune responses
  • Baseline HIV-1 RNA level
  • Baseline CD4%
  • Baseline immune activation markers
Not Provided
Not Provided
 
Optimizing Pediatric HIV-1 Treatment, Nairobi, Kenya
Optimizing Pediatric HIV-1 Treatment, Nairobi, Kenya (0-4.5 Month RCT)

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).

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)

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
HIV Infections
  • 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
  • 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.
    Interventions:
    • 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)
  • 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.
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
141
July 2013
July 2013   (final data collection date for primary outcome measure)

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.
Both
up to 54 Months
No
Contact information is only displayed when the study is recruiting subjects
Not Provided
 
NCT00428116
30201-D, 2 RO1 HD023412-16;, 06-1885-D 02
Yes
Grace John-Stewart, University of Washington
University of Washington
  • Fred Hutchinson Cancer Research Center
  • University of Nairobi
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
University of Washington
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP