Pediatric Urgent Start of Highly Active Antiretroviral Treatment (HAART)

NCT02063880 | Completed Results DMC FDA Drug

• 2 other identifiers: STUDY000010522R01HD023412-21
• Study Type: interventional
• Target: 183
• Locations: 1 country
• Sites: 4

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. 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. 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.

Conditions

Human Immunodeficiency Virus; Immune Reconstitution Inflammatory Syndrome

Keywords

HIV-1; IRIS

Outcome Measures

Primary Outcomes (1)

• All-cause Mortality

  6 months post-HAART initiation

Secondary Outcomes (2)

• Number of Participants With Evidence of Immune Reconstitution and Inflammatory Syndrome (IRIS)

  6 months post-HAART initiation

• Number of Participants With Potential Drug Toxicity

  6 months post-HAART initiation

Study Arms (2)

Urgent ART

EXPERIMENTAL

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

Early ART

ACTIVE COMPARATOR

Initiation of HAART 7-14 days after enrollment.

Other: Early ART

Interventions

Urgent ART OTHER

Children will be started on HAART \<48 hours after enrollment.

Also known as: HAART regimens recommended by WHO and Kenya MOH.

Urgent ART

Early ART OTHER

Children will be started on ART after stabilization 7-14 days after enrollment.

Early ART

Eligibility Criteria

• Age: Up to 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• University of Washington: lead
• University of Nairobi: collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (4)

JOOTRH

Kisumu, Kenya

Location

Kisumu District Hospital

Kisumu, Kenya

Location

Mbagathi District Hospital

Nairobi, 0202, Kenya

Location

Kenyatta National Hospital

Nairobi, Kenya

Location

Related Publications (6)

• Cherkos AS, Cranmer LM, Njuguna I, LaCourse SM, Mugo C, Moraa H, Maleche-Obimbo E, Enquobahrie DA, Richardson BA, Wamalwa D, John-Stewart G. Effect of tuberculosis-HIV co-treatment on clinical and growth outcomes among hospitalized children newly initiating antiretroviral therapy. AIDS. 2024 Mar 15;38(4):579-588. doi: 10.1097/QAD.0000000000003797. Epub 2023 Nov 27.

  PMID: 38016160 DERIVED

• Njuguna IN, Cranmer LM, Wagner AD, LaCourse SM, Mugo C, Benki-Nugent S, Richardson BA, Stern J, Maleche-Obimbo E, Wamalwa DC, John-Stewart G. Brief Report: Cofactors of Mortality Among Hospitalized HIV-Infected Children Initiating Antiretroviral Therapy in Kenya. J Acquir Immune Defic Syndr. 2019 Jun 1;81(2):138-144. doi: 10.1097/QAI.0000000000002012.

  PMID: 31095004 DERIVED

• LaCourse SM, Cranmer LM, Njuguna IN, Gatimu J, Stern J, Maleche-Obimbo E, Walson JL, Wamalwa D, John-Stewart GC, Pavlinac PB. Urine Tuberculosis Lipoarabinomannan Predicts Mortality in Hospitalized Human Immunodeficiency Virus-Infected Children. Clin Infect Dis. 2018 May 17;66(11):1798-1801. doi: 10.1093/cid/ciy011.

  PMID: 29324985 DERIVED

• Njuguna IN, Cranmer LM, Otieno VO, Mugo C, Okinyi HM, Benki-Nugent S, Richardson B, Stern J, Maleche-Obimbo E, Wamalwa DC, John-Stewart GC. Urgent versus post-stabilisation antiretroviral treatment in hospitalised HIV-infected children in Kenya (PUSH): a randomised controlled trial. Lancet HIV. 2018 Jan;5(1):e12-e22. doi: 10.1016/S2352-3018(17)30167-4. Epub 2017 Nov 14.

  PMID: 29150377 DERIVED

• Wagner AD, Njuguna IN, Andere RA, Cranmer LM, Okinyi HM, Benki-Nugent S, Chohan BH, Maleche-Obimbo E, Wamalwa DC, John-Stewart GC. Infant/child rapid serology tests fail to reliably assess HIV exposure among sick hospitalized infants. AIDS. 2017 Jul 17;31(11):F1-F7. doi: 10.1097/QAD.0000000000001562.

  PMID: 28609404 DERIVED

• Njuguna IN, Wagner AD, Cranmer LM, Otieno VO, Onyango JA, Chebet DJ, Okinyi HM, Benki-Nugent S, Maleche-Obimbo E, Slyker JA, John-Stewart GC, Wamalwa DC. Hospitalized Children Reveal Health Systems Gaps in the Mother-Child HIV Care Cascade in Kenya. AIDS Patient Care STDS. 2016 Mar;30(3):119-24. doi: 10.1089/apc.2015.0239.

  PMID: 27308805 DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; Immune Reconstitution Inflammatory Syndrome

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Results Point of Contact

• Title: Grace John-Stewart
• Organization: University of Washington

gjohn@uw.edu

206 5434278

Study Officials

• Grace John Stewart, MD, PhD

  University of Washington

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Global Health

Study Record Dates

• First Submitted: August 21, 2012
• First Posted: February 17, 2014
• Study Start: March 1, 2013
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2015
• Last Updated: May 14, 2018
• Results First Posted: July 25, 2017

Record last verified: 2018-04

Data Sharing

• IPD Sharing: Will share

Locations

KE (4)