Pediatric Urgent Start of Highly Active Antiretroviral Treatment (HAART)

Not Applicable

Completed

• Conditions: Human Immunodeficiency Virus; Immune Reconstitution Inflammatory Syndrome
• Interventions: Other: Urgent ART; Other: Early ART

• Registration Number: NCT02063880
• Lead Sponsor: University of Washington

Brief Summary

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.

Detailed Description

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

Study Timeline

• Study First Submitted: 2012-08-21
• Study Start: 2013-03
• Study First Submitted QC: 2014-02-13
• Study First Posted: 2014-02-17
• Primary Completion: 2015-11
• Study Completion: 2015-11
• Results First Submitted: 2017-05-01
• Results First Submitted QC: 2017-05-02
• Results First Posted: 2017-07-25
• Status Verified: 2018-04
• Last Update Submitted: 2018-04-11
• Last Update Posted: 2018-05-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 183

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Urgent ART	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.
Early ART	Early ART	Initiation of HAART 7-14 days after enrollment.

Primary Outcome Measures

Name	Time	Method
All-cause Mortality	6 months post-HAART initiation

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Evidence of Immune Reconstitution and Inflammatory Syndrome (IRIS)	6 months post-HAART initiation	Confirmed, possible or likely IRIS based on external independent review
Number of Participants With Potential Drug Toxicity	6 months post-HAART initiation	Participants with adverse events that are deemed to be potentially related to medications.

Trial Locations

Locations (4)

Mbagathi District Hospital; 🇰🇪 Nairobi, Kenya

Kisumu District Hospital; 🇰🇪 Kisumu, Kenya

JOOTRH; 🇰🇪 Kisumu, Kenya

Kenyatta National Hospital; 🇰🇪 Nairobi, Kenya