Optimizing Pediatric HIV-1 Treatment, Nairobi, Kenya

• Status: Terminated
• Trial end date: 2014-12-01
• Target enrollment: 0
• Participant gender: All

Summary

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).

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Washington
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Fred Hutchinson Cancer Research Center; National Institutes of Health (NIH); University of Nairobi

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 (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.