NCT02063880: PUSH

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

Completed NA Results posted Last updated 11 April 2018

What this trial tests

NA trial testing Urgent ART in Human Immunodeficiency Virus in 183 participants. Completed in 1 November 2015.

Timeline

1 March 2013

Primary endpoint
1 November 2015

1 November 2015

Quick facts

Lead sponsor	University of Washington
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	183
Start date	1 March 2013
Primary completion	1 November 2015
Estimated completion	1 November 2015
Sites	4 locations across Kenya

Drugs / interventions tested

• Urgent ART
• Early ART

Conditions studied

• Human Immunodeficiency Virus — all drugs for Human Immunodeficiency Virus →
• Immune Reconstitution Inflammatory Syndrome — all drugs for Immune Reconstitution Inflammatory Syndrome →

Sponsor

University of Washington

Who can join

Under 12, any sex, with Human Immunodeficiency Virus or Immune Reconstitution Inflammatory Syndrome. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• All-cause Mortality
  Time frame: 6 months post-HAART initiation

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Stool Xpert MTB/RIF and urine lipoarabinomannan for the diagnosis of tuberculosis in hospitalized HIV-infected children.
   LaCourse SM, Pavlinac PB, Cranmer LM, Njuguna IN, et al · · 2018 · cited 67× · PMID 29028662 · DOI 10.1097/qad.0000000000001662
2. Diagnosis of paediatric tuberculosis by optically detecting two virulence factors on extracellular vesicles in blood samples.
   Zheng W, LaCourse SM, Song B, Singh DK, et al · · 2022 · cited 50× · PMID 35986185 · DOI 10.1038/s41551-022-00922-1
3. Urgent versus post-stabilisation antiretroviral treatment in hospitalised HIV-infected children in Kenya (PUSH): a randomised controlled trial.
   Njuguna IN, Cranmer LM, Otieno VO, Mugo C, et al · · 2018 · cited 40× · PMID 29150377 · DOI 10.1016/s2352-3018(17)30167-4
4. Monocyte-to-Lymphocyte Ratio Is Associated With Tuberculosis Disease and Declines With Anti-TB Treatment in HIV-Infected Children.
   Choudhary RK, Wall KM, Njuguna I, Pavlinac PB, et al · · 2019 · cited 26× · PMID 30399036 · DOI 10.1097/qai.0000000000001893
5. Hospitalized Children Reveal Health Systems Gaps in the Mother-Child HIV Care Cascade in Kenya.
   Njuguna IN, Wagner AD, Cranmer LM, Otieno VO, et al · · 2016 · cited 20× · PMID 27308805 · DOI 10.1089/apc.2015.0239
6. Improved Neurodevelopment After Initiation of Antiretroviral Therapy in Human Immunodeficiency Virus-infected Children.
   Gómez LA, Crowell CS, Njuguna I, Cranmer LM, et al · · 2018 · cited 15× · PMID 29438131 · DOI 10.1097/inf.0000000000001942
7. Urine Tuberculosis Lipoarabinomannan Predicts Mortality in Hospitalized Human Immunodeficiency Virus-Infected Children.
   LaCourse SM, Cranmer LM, Njuguna IN, Gatimu J, et al · · 2018 · cited 10× · PMID 29324985 · DOI 10.1093/cid/ciy011
8. Development of a Clinical Prediction Score Including Monocyte-to-Lymphocyte Ratio to Inform Tuberculosis Treatment Among Children With HIV: A Multicountry Study.
   Malik AA, Gandhi NR, Marcy O, Walters E, et al · · 2022 · cited 9× · PMID 36381621 · DOI 10.1093/ofid/ofac548