Clinical trial NCT00234091: When to Start Anti-HIV Drugs in Children Infected With HIV (The PREDICT Study)
Official title: An Open Label, Randomized Study to Compare Antiretroviral Therapy (ART) Initiation When CD4 is Between 15% to 24% to ART Initiation When CD4 Falls Below 15% in Children With HIV Infection and Moderate Immune Suppression
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infections
Keywords: Treatment Naive
Treatment Initiation
Infant
Preschool Child
Child
Zidovudine
AZT
Retrovir
3TC
Lamivudine
Epivir
Nevirapine
NVP
Viramune
Efavirenz
EFV
Sustiva
Lopinavir/Ritonavir
LPV/r
Kaletra
Nelfinavir
NFV
Viracept
ABC
Abacavir
Ziagen
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Comprehensive International Program of Research on AIDS
First posted: 2005-10-06
Enrollment: 300
Sex: ALL
Minimum age (years): 1
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine when HIV infected children should begin taking anti-HIV medications in order to improve both patient quality of life and survival.

Detailed description: The use of highly active antiretroviral therapy (HAART) has resulted in a significant reduction in AIDS-related deaths and complications among adults and adolescents. However, the medical management of HIV infected children remains challenging. Access to HIV treatment is limited and early treatment initiation can cause serious complications. Since there is currently no cure for HIV, a balance between treating the disease and maintaining quality of life must be weighed carefully. An evaluation to determine the appropriate time to initiate HAART is necessary to improve both quality of life and survival for HIV infected children.

This study will last 144 weeks. All participants will have a CD4 percentage (CD4%) between 15% and 24% and will be randomly assigned to either receive immediate or delayed HAART. The HAART regimen will consist of two nucleoside reverse transcriptase inhibitors, zidovudine and lamivudine. In addition, participants will also receive either one non-nucleoside reverse transcriptase inhibitor, nevirapine or efavirenz, or one protease inhibitor, ritonavir-boosted lopinavir or nelfinavir. Abacavir will replace zidovudine or lamivudine if participants experience toxicity to the regimen. Participants in the immediate treatment arm will receive HAART on Day 1 of the study regardless of their CD4%. Participants in the delayed treatment arm will receive HAART if their CD4% falls below 15 or if they develop a CDC Category C illness.

Study visits will occur every 4 weeks for the first 12 weeks and then every 12 weeks until the end of the study. Blood collection, physical exams, and medical and medication history reviews will occur at all visits. Adherence, quality of life, and lipodystrophy assessments will occur every 12 weeks for participants on HAART. Participants will be encouraged to enroll in a related substudy to examine the neurodevelopment of HIV infected children.

Eligibility criteria: Inclusion Criteria:

* HIV-1 infected
* Antiretroviral naive, defined as never receiving anti-HIV medications, receiving them for less than 7 days, or only receiving them to prevent mother-to-child transmission (MTCT)
* CD4% between 15 and 24 within 30 days prior to study entry
* CDC pediatric clinical classification A or B
* Parent or guardian willing to provide informed consent and willing to follow all study procedures and requirements

Exclusion Criteria:

* Use of systemic chemotherapy, immunomodulators, HIV vaccines, immune globulin, interleukins, or interferons within 30 days prior to study entry
* Active AIDS-defining illnesses (CDC Category C) within 30 days prior to study entry
* Certain abnormal laboratory values
* Known kidney disease
* Known allergy or sensitivity to study drugs
* Require certain medications
* Pregnancy

Primary outcomes:
measure: AIDS-free survival
timeFrame: Week 144
Secondary outcomes:
measure: Direct and indirect cost of treatment per patient
timeFrame: Week 144
measure: Number and duration of hospitalizations
timeFrame: throughout study
measure: Time to and number of Grades 3 or 4 HAART-related toxicity and intolerance
timeFrame: throughout study
measure: Number of HAART regimen changes
timeFrame: throughout study
measure: Number of Grades 1 or 2 infectious episodes
timeFrame: throughout study
measure: Number of courses of antibiotics used
timeFrame: throughout study
measure: Number of HIV-related clinical events
timeFrame: throughout study
measure: Virologic failure, defined as HIV viral load of 1000 copies/ml
timeFrame: Week 24 after HAART initiation
measure: Presence of a resistance mutation in participants with virologic failure
timeFrame: throughout study
measure: Change of growth in Z scores
timeFrame: study entry to Week 144
measure: Change in CD4% and time-weighted average change
timeFrame: study entry and Week 144
measure: CD4 less than 10%
timeFrame: Week 144
measure: Average scores of the child's quality of life over time
timeFrame: Week 144
measure: Percentage adherence to HAART over time by pill count/weighing liquid medication bottles, self report, and questionnaire
timeFrame: throughout study
measure: Presence of iron deficiency anemia
timeFrame: study entry and Weeks 24, 48, 72, 96, 120, and 144
measure: HIV viral sequence
timeFrame: study entry and treatment failure
measure: HIV viral replication capacity
timeFrame: throughout study
measure: Cytotoxic T-cell (CTL) response
timeFrame: throughout study
measure: Percentage of different T-cell subsets
timeFrame: study entry and Weeks 48, 96, and 144
Other outcomes:
Locations:
city: Phnom Penh
country: Cambodia
facility: National Pediatric Hosp., Cambodia CIPRA CRS
city: Phnom Penh
country: Cambodia
facility: Social Health Clinic, Cambodia CIPRA CRS
city: Pathumwan
country: Thailand
facility: Hiv-Nat Cipra Crs
state: Bangkok
city: Muang
country: Thailand
facility: Chiang Rai Regional Hosp. CIPRA CRS
state: Chiang Rai
city: Chantaburi
country: Thailand
facility: Prapokklao Hosp. CIPRA CRS
city: Chiang Mai
country: Thailand
facility: Nakornping Hosp. CIPRA CRS
city: Chonburi
country: Thailand
facility: Queen Savang Vadhana Memorial Hosp. CIPRA CRS
city: Khon Kaen
country: Thailand
facility: Srinagarind Hosp. CIPRA CRS
city: Nonthaburi
country: Thailand
facility: Bamrasnaradura Institute CIPRA CRS
Study officials:
affiliation: Department of Medicine at Chulalongkorn University, Bangkok, Thailand
name: Kiat Ruxrungtham, MD, MPH
role: STUDY_CHAIR
affiliation: National Center for HIV/AIDS Dermatology and STDs, Phnom Penh, Cambodia
name: Saphonn Vonthanak, MD, PhD
role: STUDY_CHAIR
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