Pediatric Urgent Start of Highly Active Antiretroviral Treatment (HAART)

Human Immunodeficiency Virus Clinical Trial

— PUSH  

Official title:

Urgent Versus Post-Stabilization ART in HIV-1 Infected Children With Severe Co-Infections

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02063880
• Other study ID #: STUDY00001052
• Secondary ID: 2R01HD023412-21
• Status: Completed
• Phase: N/A
• Start date: March 2013
• Est. completion date: November 2015

Study information

• Verified date: April 2018
• Source: University of Washington
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 183
• Est. completion date: November 2015
• Est. primary completion date: November 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 12 Years

Eligibility

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

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• Human Immunodeficiency Virus
• Immune Reconstitution Inflammatory Syndrome
• Immunologic Deficiency Syndromes

Intervention

Other:
• Urgent ART
Children will be started on HAART <48 hours after enrollment.
• Early ART
Children will be started on ART after stabilization 7-14 days after enrollment.

Locations

Country	Name	City	State
Kenya	JOOTRH	Kisumu
Kenya	Kisumu District Hospital	Kisumu
Kenya	Kenyatta National Hospital	Nairobi
Kenya	Mbagathi District Hospital	Nairobi

Sponsors (3)

Lead Sponsor	Collaborator
University of Washington	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), University of Nairobi

Country where clinical trial is conducted

Kenya, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	All-cause Mortality		6 months post-HAART initiation
Secondary	Number of Participants With Evidence of Immune Reconstitution and Inflammatory Syndrome (IRIS)	Confirmed, possible or likely IRIS based on external independent review	6 months post-HAART initiation
Secondary	Number of Participants With Potential Drug Toxicity	Participants with adverse events that are deemed to be potentially related to medications.	6 months post-HAART initiation