Pediatric Urgent Start of Highly Active Antiretroviral Treatment (HAART) (PUSH)

University of Washington

Status: Completed

Conditions: Human Immunodeficiency Virus; Immune Reconstitution Inflammatory Syndrome

Treatments: Other: Early ART; Other: Urgent ART

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02063880

STUDY00001052

2R01HD023412-21 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Primary hypothesis:

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.

Secondary hypotheses:

Urgent ART during an acute infection could potentially result in increased risk of immune reconstitution inflammatory syndrome (IRIS) or drug toxicities/interactions.

Specific aims:

1. 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).
2. 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.

Full description

Children will be followed and compared for 6-month mortality.

Enrollment: 183 patients

Sex: All

Ages: Under 12 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Aged ≤ 12 years old (reported)
• HIV-1 positive (for example, two rapid HIV-1 antibody tests for children >18 months and not breastfeeding, or one HIV-1 DNA/RNA test for children ≤18 months or who are breastfeeding)
• Not currently receiving antiretroviral therapy (history of pMTCT does not affect eligibility)
• Eligible to receive ART, according to current WHO guidelines
• Caregiver plans to reside in study catchment area for at least 6 months (reported)
• Caregiver provides sufficient locator information

Exclusion criteria

• Suspected meningitis, any other central nervous system infection, or encephalitis

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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183 participants in 2 patient groups

Urgent ART

Experimental group

Description:

Initiation of highly active antiretroviral therapy (HAART) within 48 hours of enrollment. Antiretroviral therapy will include regimens recommended by the Kenyan Ministry of Health.

Treatment:

Other: Urgent ART

Early ART

Active Comparator group

Description:

Initiation of HAART 7-14 days after enrollment.

Treatment:

Other: Early ART