Optimizing Pediatric HIV-1 Treatment, Nairobi, Kenya

June 29, 2018 updated by: Grace John-Stewart, University of Washington

Optimizing Pediatric HIV-1 Treatment, Nairobi, Kenya (0-4.5 Month Randomized Controlled Trial)

Given the high mortality associated with infant HIV-1 and the fact that surrogate markers are poorly predictive of mortality risk,empiric highly active antiretroviral therapy (HAART) initiation is started 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).

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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))

Study Type

Interventional

Enrollment (Actual)

140

Phase

  • Not Applicable

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 4 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 (WHZ) > -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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Active Comparator: 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: HAART
Combination first line antiretrovirals as previously described.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Growth at 18 Months Post-randomization
Time Frame: 18 months of post-randomization follow-up
Weight and height will be transformed to the weight-for-age Z-score (i.e., WAZ) and height-for-age Z-score (i.e., HAZ) using World Health Organization Child Growth Standards, taking into account the infant's age and gender.
18 months of post-randomization follow-up

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Morbidity
Time Frame: 18 months post-randomization
severe adverse events including death, pneumonia, diarrhea, and other adverse events
18 months post-randomization

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Washington

Collaborators

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institutes of Health (NIH)
Fred Hutchinson Cancer Center
University of Nairobi

Investigators

  • Principal Investigator: Grace C John-Stewart, MD, PhD, University of Washington
  • Principal Investigator: Dalton Wamalwa, MMed, MPH, Department of Paediatrics and Child Health, Kenyatta National Hospital, University of Nairobi

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2007

Primary Completion (Actual)

July 1, 2013

Study Completion (Actual)

December 1, 2014

Study Registration Dates

First Submitted

January 22, 2007

First Submitted That Met QC Criteria

January 26, 2007

First Posted (Estimate)

January 29, 2007

Study Record Updates

Last Update Posted (Actual)

July 26, 2018

Last Update Submitted That Met QC Criteria

June 29, 2018

Last Verified

June 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STUDY00001675
  • R01HD023412 (U.S. NIH Grant/Contract)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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