When to Start Anti-HIV Drugs in Children Infected With HIV (The PREDICT Study)

NCT ID: NCT00234091

Last Updated: 2013-12-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

300 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-04-30

Study Completion Date

2011-09-30

Brief Summary

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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

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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.

Conditions

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HIV Infections

Keywords

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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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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1

Immediate treatment; individuals receive HAART on Day 1 of the study

Group Type ACTIVE_COMPARATOR

Abacavir

Intervention Type DRUG

8 mg/kg (up to 300 mg/dose) take orally twice daily

Efavirenz

Intervention Type DRUG

200 to 600 mg taken orally once daily

Lamivudine

Intervention Type DRUG

4 mg/kg (up to 150 mg/dose) taken orally twice daily

Lopinavir/Ritonavir

Intervention Type DRUG

230 mg/57.5 mg/m\^2 body surface area taken orally twice daily with food

Nelfinavir

Intervention Type DRUG

45-55 mg/kg taken orally twice daily with food

Nevirapine

Intervention Type DRUG

120 mg/m\^2 once daily for first 14 days, tehn 200 mg/m\^2 (up to 400 mg/day) twice daily

Zidovudine

Intervention Type DRUG

180-240 mg/m\^2 every 12 hours (up to 300 mg/dose)

2

Delayed treatment; individuals receive HAART if their CD4 percentage falls below 15 percentage OR if they develop a CDC category C illness

Group Type ACTIVE_COMPARATOR

Abacavir

Intervention Type DRUG

8 mg/kg (up to 300 mg/dose) take orally twice daily

Efavirenz

Intervention Type DRUG

200 to 600 mg taken orally once daily

Lamivudine

Intervention Type DRUG

4 mg/kg (up to 150 mg/dose) taken orally twice daily

Lopinavir/Ritonavir

Intervention Type DRUG

230 mg/57.5 mg/m\^2 body surface area taken orally twice daily with food

Nelfinavir

Intervention Type DRUG

45-55 mg/kg taken orally twice daily with food

Nevirapine

Intervention Type DRUG

120 mg/m\^2 once daily for first 14 days, tehn 200 mg/m\^2 (up to 400 mg/day) twice daily

Zidovudine

Intervention Type DRUG

180-240 mg/m\^2 every 12 hours (up to 300 mg/dose)

Interventions

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Abacavir

8 mg/kg (up to 300 mg/dose) take orally twice daily

Intervention Type DRUG

Efavirenz

200 to 600 mg taken orally once daily

Intervention Type DRUG

Lamivudine

4 mg/kg (up to 150 mg/dose) taken orally twice daily

Intervention Type DRUG

Lopinavir/Ritonavir

230 mg/57.5 mg/m\^2 body surface area taken orally twice daily with food

Intervention Type DRUG

Nelfinavir

45-55 mg/kg taken orally twice daily with food

Intervention Type DRUG

Nevirapine

120 mg/m\^2 once daily for first 14 days, tehn 200 mg/m\^2 (up to 400 mg/day) twice daily

Intervention Type DRUG

Zidovudine

180-240 mg/m\^2 every 12 hours (up to 300 mg/dose)

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

1 Year

Maximum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Comprehensive International Program of Research on AIDS

OTHER

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Kiat Ruxrungtham, MD, MPH

Role: STUDY_CHAIR

Department of Medicine at Chulalongkorn University, Bangkok, Thailand

Saphonn Vonthanak, MD, PhD

Role: STUDY_CHAIR

National Center for HIV/AIDS Dermatology and STDs, Phnom Penh, Cambodia

Locations

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National Pediatric Hosp., Cambodia CIPRA CRS

Phnom Penh, , Cambodia

Site Status

Social Health Clinic, Cambodia CIPRA CRS

Phnom Penh, , Cambodia

Site Status

Hiv-Nat Cipra Crs

Pathumwan, Bangkok, Thailand

Site Status

Chiang Rai Regional Hosp. CIPRA CRS

Muang, Changwat Chiang Rai, Thailand

Site Status

Prapokklao Hosp. CIPRA CRS

Chanthaburi, , Thailand

Site Status

Nakornping Hosp. CIPRA CRS

Chiang Mai, , Thailand

Site Status

Queen Savang Vadhana Memorial Hosp. CIPRA CRS

Chon Buri, , Thailand

Site Status

Srinagarind Hosp. CIPRA CRS

Khon Kaen, , Thailand

Site Status

Bamrasnaradura Institute CIPRA CRS

Nonthaburi, , Thailand

Site Status

Countries

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Cambodia Thailand

References

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Lindsey JC, Malee KM, Brouwers P, Hughes MD; PACTG 219C Study Team. Neurodevelopmental functioning in HIV-infected infants and young children before and after the introduction of protease inhibitor-based highly active antiretroviral therapy. Pediatrics. 2007 Mar;119(3):e681-93. doi: 10.1542/peds.2006-1145. Epub 2007 Feb 12.

Reference Type BACKGROUND
PMID: 17296781 (View on PubMed)

Nikolic-Djokic D, Essajee S, Rigaud M, Kaul A, Chandwani S, Hoover W, Lawrence R, Pollack H, Sitnitskaya Y, Hagmann S, Jean-Philippe P, Chen SH, Radding J, Krasinski K, Borkowsky W. Immunoreconstitution in children receiving highly active antiretroviral therapy depends on the CD4 cell percentage at baseline. J Infect Dis. 2002 Feb 1;185(3):290-8. doi: 10.1086/338567. Epub 2002 Jan 8.

Reference Type BACKGROUND
PMID: 11807710 (View on PubMed)

Puthanakit T, Aurpibul L, Oberdorfer P, Akarathum N, Kanjananit S, Wannarit P, Sirisanthana T, Sirisanthana V. Hospitalization and mortality among HIV-infected children after receiving highly active antiretroviral therapy. Clin Infect Dis. 2007 Feb 15;44(4):599-604. doi: 10.1086/510489. Epub 2007 Jan 9.

Reference Type BACKGROUND
PMID: 17243067 (View on PubMed)

Walker AS, Doerholt K, Sharland M, Gibb DM; Collaborative HIV Paediatric Study (CHIPS) Steering Committee. Response to highly active antiretroviral therapy varies with age: the UK and Ireland Collaborative HIV Paediatric Study. AIDS. 2004 Sep 24;18(14):1915-24. doi: 10.1097/00002030-200409240-00007.

Reference Type BACKGROUND
PMID: 15353977 (View on PubMed)

Paul RH, Cho KS, Belden AC, Mellins CA, Malee KM, Robbins RN, Salminen LE, Kerr SJ, Adhikari B, Garcia-Egan PM, Sophonphan J, Aurpibul L, Thongpibul K, Kosalaraksa P, Kanjanavanit S, Ngampiyaskul C, Wongsawat J, Vonthanak S, Suwanlerk T, Valcour VG, Preston-Campbell RN, Bolzenious JD, Robb ML, Ananworanich J, Puthanakit T; PREDICT Study Group. Machine-learning classification of neurocognitive performance in children with perinatal HIV initiating de novo antiretroviral therapy. AIDS. 2020 Apr 1;34(5):737-748. doi: 10.1097/QAD.0000000000002471.

Reference Type DERIVED
PMID: 31895148 (View on PubMed)

Paul R, Apornpong T, Prasitsuebsai W, Puthanakit T, Saphonn V, Aurpibul L, Kosalaraksa P, Kanjanavanit S, Luesomboon W, Ngampiyaskul C, Suwanlerk T, Chettra K, Shearer WT, Valcour V, Ananworanich J, Kerr S. Cognition, Emotional Health, and Immunological Markers in Children With Long-Term Nonprogressive HIV. J Acquir Immune Defic Syndr. 2018 Apr 1;77(4):417-426. doi: 10.1097/QAI.0000000000001619.

Reference Type DERIVED
PMID: 29303843 (View on PubMed)

Paul R, Prasitsuebsai W, Jahanshad N, Puthanakit T, Thompson P, Aurpibul L, Hansudewechakul R, Kosalaraksa P, Kanjanavanit S, Ngampiyaskul C, Luesomboon W, Lerdlum S, Pothisri M, Visrutaratna P, Valcour V, Nir TM, Saremi A, Kerr S, Ananworanich J; Pediatric Randomized Early versus Deferred Initiation in Cambodia and Thailand (PREDICT) Study Group. Structural Neuroimaging and Neuropsychologic Signatures in Children With Vertically Acquired HIV. Pediatr Infect Dis J. 2018 Jul;37(7):662-668. doi: 10.1097/INF.0000000000001852.

Reference Type DERIVED
PMID: 29200184 (View on PubMed)

Bunupuradah T, Hansudewechakul R, Kosalaraksa P, Ngampiyaskul C, Kanjanavanit S, Wongsawat J, Luesomboon W, Sophonphan J, Puthanakit T, Ruxrungtham K, Shearer WT, Ananworanich J; PREDICT study group. HLA-DRB1454 and predictors of new-onset asthma in HIV-infected Thai children. Clin Immunol. 2015 Mar;157(1):26-9. doi: 10.1016/j.clim.2014.12.006. Epub 2014 Dec 26. No abstract available.

Reference Type DERIVED
PMID: 25546395 (View on PubMed)

Intasan J, Bunupuradah T, Vonthanak S, Kosalaraksa P, Hansudewechakul R, Kanjanavanit S, Ngampiyaskul C, Wongsawat J, Luesomboon W, Apornpong T, Kerr S, Ananworanich J, Puthanakit T; PREDICT Study Group. Comparison of adherence monitoring tools and correlation to virologic failure in a pediatric HIV clinical trial. AIDS Patient Care STDS. 2014 Jun;28(6):296-302. doi: 10.1089/apc.2013.0276.

Reference Type DERIVED
PMID: 24901463 (View on PubMed)

Puthanakit T, Saphonn V, Ananworanich J, Kosalaraksa P, Hansudewechakul R, Vibol U, Kerr SJ, Kanjanavanit S, Ngampiyaskul C, Wongsawat J, Luesomboon W, Ngo-Giang-Huong N, Chettra K, Cheunyam T, Suwarnlerk T, Ubolyam S, Shearer WT, Paul R, Mofenson LM, Fox L, Law MG, Cooper DA, Phanuphak P, Vun MC, Ruxrungtham K; PREDICT Study Group. Early versus deferred antiretroviral therapy for children older than 1 year infected with HIV (PREDICT): a multicentre, randomised, open-label trial. Lancet Infect Dis. 2012 Dec;12(12):933-41. doi: 10.1016/S1473-3099(12)70242-6. Epub 2012 Oct 9.

Reference Type DERIVED
PMID: 23059199 (View on PubMed)

Kosalaraksa P, Bunupuradah T, Vonthanak S, Wiangnon S, Hansudewechakul R, Vibol U, Kanjanavanit S, Ngampiyaskul C, Wongsawat J, Luesomboon W, Lumbiganon P, Sopa B, Apornpong T, Chuenyam T, Cooper DA, Ruxrungtham K, Ananworanich J, Puthanakit T. Prevalence of anemia and underlying iron status in naive antiretroviral therapy HIV-infected children with moderate immune suppression. AIDS Res Hum Retroviruses. 2012 Dec;28(12):1679-86. doi: 10.1089/AID.2011.0373. Epub 2012 Jul 25.

Reference Type DERIVED
PMID: 22734817 (View on PubMed)

Bunupuradah T, Ubolyam S, Hansudewechakul R, Kosalaraksa P, Ngampiyaskul C, Kanjanavanit S, Wongsawat J, Luesomboon W, Pinyakorn S, Kerr S, Ananworanich J, Chomtho S, van der Lugt J, Luplertlop N, Ruxrungtham K, Puthanakit T; PREDICT study group. Correlation of selenium and zinc levels to antiretroviral treatment outcomes in Thai HIV-infected children without severe HIV symptoms. Eur J Clin Nutr. 2012 Aug;66(8):900-5. doi: 10.1038/ejcn.2012.57. Epub 2012 Jun 20.

Reference Type DERIVED
PMID: 22713768 (View on PubMed)

Kanjanavanit S, Puthanakit T, Vibol U, Kosalaraksa P, Hansudewechakul R, Ngampiyasakul C, Wongsawat J, Luesomboon W, Wongsabut J, Mahanontharit A, Suwanlerk T, Saphonn V, Ananworanich J, Ruxrungtham K; PREDICT study group. High prevalence of lipid abnormalities among antiretroviral-naive HIV-infected Asian children with mild-to-moderate immunosuppression. Antivir Ther. 2011;16(8):1351-5. doi: 10.3851/IMP1897.

Reference Type DERIVED
PMID: 22155918 (View on PubMed)

Bunupuradah T, Puthanakit T, Kosalaraksa P, Kerr SJ, Kariminia A, Hansudewechakul R, Kanjanavanit S, Ngampiyaskul C, Wongsawat J, Luesomboon W, Chuenyam T, Vonthanak S, Vun MC, Vibol U, Vannary B, Ruxrungtham K, Ananworanich J; PREDICT Study Group. Poor quality of life among untreated Thai and Cambodian children without severe HIV symptoms. AIDS Care. 2012;24(1):30-8. doi: 10.1080/09540121.2011.592815. Epub 2011 Jul 21.

Reference Type DERIVED
PMID: 21777076 (View on PubMed)

Ananworanich J, Apornpong T, Kosalaraksa P, Jaimulwong T, Hansudewechakul R, Pancharoen C, Bunupuradah T, Chandara M, Puthanakit T, Ngampiyasakul C, Wongsawat J, Kanjanavanit S, Luesomboon W, Klangsinsirikul P, Ngo-Giang-Huong N, Kerr SJ, Ubolyam S, Mengthaisong T, Gelman RS, Pattanapanyasat K, Saphonn V, Ruxrungtham K, Shearer WT; PREDICT Study Group. Characteristics of lymphocyte subsets in HIV-infected, long-term nonprogressor, and healthy Asian children through 12 years of age. J Allergy Clin Immunol. 2010 Dec;126(6):1294-301.e10. doi: 10.1016/j.jaci.2010.09.038.

Reference Type DERIVED
PMID: 21134574 (View on PubMed)

Wongsawat J, Puthanakit T, Kanjanavanit S, Hansudewechakul R, Ngampiyaskul C, Kerr SJ, Ubolyam S, Suwanlerk T, Kosalaraksa P, Luesomboon W, Ngo-Giang-Huong N, Chandara M, Saphonn V, Ruxrungtham K, Ananworanich J; PREDICT Study Group. CD4 cell count criteria to determine when to initiate antiretroviral therapy in human immunodeficiency virus-infected children. Pediatr Infect Dis J. 2010 Oct;29(10):966-8. doi: 10.1097/INF.0b013e3181e0554c.

Reference Type DERIVED
PMID: 20418798 (View on PubMed)

Related Links

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http://www.hivnat.org

Click here for more information about the HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT)

Other Identifiers

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PREDICT

Identifier Type: -

Identifier Source: secondary_id

10409

Identifier Type: REGISTRY

Identifier Source: secondary_id

CIPRA TH001

Identifier Type: -

Identifier Source: org_study_id