Pediatric Urgent Start of Highly Active Antiretroviral Treatment (HAART) (PUSH)
Design: Randomized clinical trial involving hospitalized HIV-1 infected children. Children will be randomized to randomized to urgent (<48 hours) versus early antiretroviral therapy (7-14 days). This trial will be unblinded.
Population: Hospitalized HIV-1 infected children who are antiretroviral therapy (ART) naïve ≤ 12 years of age.
Sample size: 360 children will be randomized (180 per arm).
Treatment: All infants will be treated with ART according to World Health Organization (WHO) and Kenyan national guidelines.
Study duration: Enrollment into the study will occur over the course of 36-48 months and each infant will be routinely followed for a maximum of 6 months.
Study site: Kenyan hospitals.
HIV-1 infected children hospitalized with severe co-infection either may be unsalvageable due to too far advanced immunosuppression/co-infection or may benefit from urgent ART.
Urgent ART during an acute infection could potentially result in increased risk of immune reconstitution inflammatory syndrome (IRIS) or drug toxicities/interactions.
- To compare the 6 month all-cause mortality rate, incidence of immune reconstitution inflammatory syndrome (IRIS), and incidence of drug toxicity in HIV-1 infected children (≤ 12 years old) presenting to hospital with a serious infection randomized to urgent (<48 hours) versus early ART (7-14 days).
- To determine co-factors for mortality, IRIS, and drug toxicity. Potential cofactors will include: baseline weight-for-age, height-for-age, weight-for-height (Z-scores), CD4, HIV-1 RNA, type of co-infection, age, rate of viral load and CD4 change following ART, immune activation markers, pathogen and HIV-1 specific immune responses.
Secondary aim: To determine etiologies of IRIS and to compare immune reconstitution to HIV, TB, EBV and CMV following ART overall and in each trial arm.
Human Immunodeficiency Virus
Immune Reconstitution Inflammatory Syndrome
Other: Urgent ART
Other: Early ART
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Urgent Versus Post-Stabilization ART in HIV-1 Infected Children With Severe Co-Infections|
- All-cause mortality [ Time Frame: 6 months post-HAART initiation ] [ Designated as safety issue: Yes ]
- Immune Reconstitution and Inflammatory Syndrome (IRIS) [ Time Frame: 6 months post-HAART initiation ] [ Designated as safety issue: Yes ]
- Drug toxicity [ Time Frame: 6 months post-HAART initiation ] [ Designated as safety issue: Yes ]
|Study Start Date:||March 2013|
|Study Completion Date:||November 2015|
|Primary Completion Date:||November 2015 (Final data collection date for primary outcome measure)|
Experimental: Urgent ART
Initiation of highly active antiretroviral therapy (HAART) within 48 hours of enrollment.
Antiretroviral therapy will include regimens recommended by the Kenyan Ministry of Health.
Other: Urgent ART
Children will be started on HAART <48 hours after enrollment.
Other Name: HAART regimens recommended by WHO and Kenya MOH.
Active Comparator: Early ART
Initiation of HAART 7-14 days after enrollment.
Other: Early ART
Children will be started on ART after stabilization 7-14 days after enrollment.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02063880
|Kisumu District Hospital|
|Mbagathi District Hospital|
|Nairobi, Kenya, 0202|
|Kenyatta National Hospital|
|Principal Investigator:||Grace John Stewart, MD, PhD||University of Washington|