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
Intervention Model: Parallel Assignment
Masking: None (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 ]
- Immune Reconstitution and Inflammatory Syndrome (IRIS) [ Time Frame: 6 months post-HAART initiation ]Confirmed, possible or likely IRIS based on external independent review
- Drug Toxicity [ Time Frame: 6 months post-HAART initiation ]
|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|