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

This study has been completed.

Sponsor:

Collaborator:

Comprehensive International Program of Research on AIDS

Information provided by (Responsible Party):

National Institute of Allergy and Infectious Diseases (NIAID)

ClinicalTrials.gov Identifier:

NCT00234091

First received: October 4, 2005

Last updated: December 2, 2013

Last verified: December 2013

History of Changes

Purpose

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.

Condition	Intervention	Phase
HIV Infections	Drug: Abacavir Drug: Efavirenz Drug: Lamivudine Drug: Lopinavir/Ritonavir Drug: Nelfinavir Drug: Nevirapine Drug: Zidovudine	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Zidovudine Nevirapine Lamivudine Abacavir Efavirenz Ritonavir Nelfinavir Nelfinavir Mesylate Abacavir sulfate Lopinavir Nevirapine hemihydrate

Genetic and Rare Diseases Information Center resources: Children's Interstitial Lung Disease

U.S. FDA Resources

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:

AIDS-free survival [ Time Frame: Week 144 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Direct and indirect cost of treatment per patient [ Time Frame: Week 144 ] [ Designated as safety issue: No ]
Number and duration of hospitalizations [ Time Frame: throughout study ] [ Designated as safety issue: No ]
Time to and number of Grades 3 or 4 HAART-related toxicity and intolerance [ Time Frame: throughout study ] [ Designated as safety issue: Yes ]
Number of HAART regimen changes [ Time Frame: throughout study ] [ Designated as safety issue: No ]
Number of Grades 1 or 2 infectious episodes [ Time Frame: throughout study ] [ Designated as safety issue: No ]
Number of courses of antibiotics used [ Time Frame: throughout study ] [ Designated as safety issue: No ]
Number of HIV-related clinical events [ Time Frame: throughout study ] [ Designated as safety issue: No ]
Virologic failure, defined as HIV viral load of 1000 copies/ml [ Time Frame: Week 24 after HAART initiation ] [ Designated as safety issue: No ]
Presence of a resistance mutation in participants with virologic failure [ Time Frame: throughout study ] [ Designated as safety issue: No ]
Change of growth in Z scores [ Time Frame: study entry to Week 144 ] [ Designated as safety issue: No ]
Change in CD4% and time-weighted average change [ Time Frame: study entry and Week 144 ] [ Designated as safety issue: No ]
CD4 less than 10% [ Time Frame: Week 144 ] [ Designated as safety issue: No ]
Average scores of the child's quality of life over time [ Time Frame: Week 144 ] [ Designated as safety issue: No ]
Percentage adherence to HAART over time by pill count/weighing liquid medication bottles, self report, and questionnaire [ Time Frame: throughout study ] [ Designated as safety issue: No ]
Presence of iron deficiency anemia [ Time Frame: study entry and Weeks 24, 48, 72, 96, 120, and 144 ] [ Designated as safety issue: No ]
HIV viral sequence [ Time Frame: study entry and treatment failure ] [ Designated as safety issue: No ]
HIV viral replication capacity [ Time Frame: throughout study ] [ Designated as safety issue: No ]
Cytotoxic T-cell (CTL) response [ Time Frame: throughout study ] [ Designated as safety issue: No ]
Percentage of different T-cell subsets [ Time Frame: study entry and Weeks 48, 96, and 144 ] [ Designated as safety issue: No ]


Enrollment:	300
Study Start Date:	April 2006
Study Completion Date:	September 2011
Primary Completion Date:	September 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 1 Immediate treatment; individuals receive HAART on Day 1 of the study	Drug: Abacavir 8 mg/kg (up to 300 mg/dose) take orally twice daily Drug: Efavirenz 200 to 600 mg taken orally once daily Drug: Lamivudine 4 mg/kg (up to 150 mg/dose) taken orally twice daily Drug: Lopinavir/Ritonavir 230 mg/57.5 mg/m^2 body surface area taken orally twice daily with food Drug: Nelfinavir 45-55 mg/kg taken orally twice daily with food Drug: Nevirapine 120 mg/m^2 once daily for first 14 days, tehn 200 mg/m^2 (up to 400 mg/day) twice daily Drug: Zidovudine 180-240 mg/m^2 every 12 hours (up to 300 mg/dose)
Active Comparator: 2 Delayed treatment; individuals receive HAART if their CD4 percentage falls below 15 percentage OR if they develop a CDC category C illness	Drug: Abacavir 8 mg/kg (up to 300 mg/dose) take orally twice daily Drug: Efavirenz 200 to 600 mg taken orally once daily Drug: Lamivudine 4 mg/kg (up to 150 mg/dose) taken orally twice daily Drug: Lopinavir/Ritonavir 230 mg/57.5 mg/m^2 body surface area taken orally twice daily with food Drug: Nelfinavir 45-55 mg/kg taken orally twice daily with food Drug: Nevirapine 120 mg/m^2 once daily for first 14 days, tehn 200 mg/m^2 (up to 400 mg/day) twice daily Drug: Zidovudine 180-240 mg/m^2 every 12 hours (up to 300 mg/dose)

Arms

Assigned Interventions

Active Comparator: 1

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

Drug: Abacavir

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

Drug: Efavirenz

200 to 600 mg taken orally once daily

Drug: Lamivudine

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

Drug: Lopinavir/Ritonavir

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

Drug: Nelfinavir

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

Drug: Nevirapine

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

Drug: Zidovudine

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

Active Comparator: 2

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

Drug: Abacavir

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

Drug: Efavirenz

200 to 600 mg taken orally once daily

Drug: Lamivudine

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

Drug: Lopinavir/Ritonavir

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

Drug: Nelfinavir

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

Drug: Nevirapine

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

Drug: Zidovudine

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

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


Ages Eligible for Study:	1 Year to 12 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00234091

Locations


Cambodia
National Pediatric Hosp., Cambodia CIPRA CRS
Phnom Penh, Cambodia
Social Health Clinic, Cambodia CIPRA CRS
Phnom Penh, Cambodia
Thailand
Hiv-Nat Cipra Crs
Pathumwan, Bangkok, Thailand, 10330
Chiang Rai Regional Hosp. CIPRA CRS
Muang, Chiang Rai, Thailand, 57000
Prapokklao Hosp. CIPRA CRS
Chantaburi, Thailand, 22000
Nakornping Hosp. CIPRA CRS
Chiang Mai, Thailand, 50180
Queen Savang Vadhana Memorial Hosp. CIPRA CRS
Chonburi, Thailand, 20110
Srinagarind Hosp. CIPRA CRS
Khon Kaen, Thailand, 40002
Bamrasnaradura Institute CIPRA CRS
Nonthaburi, Thailand, 11000

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Comprehensive International Program of Research on AIDS

Investigators


Study Chair:	Kiat Ruxrungtham, MD, MPH	Department of Medicine at Chulalongkorn University, Bangkok, Thailand
Study Chair:	Saphonn Vonthanak, MD, PhD	National Center for HIV/AIDS, Dermatology, and STDs, Phnom Penh, Cambodia

More Information

Additional Information:

Click here for more information about abacavir This link exits the ClinicalTrials.gov site

Click here for more information about efavirenz This link exits the ClinicalTrials.gov site

Click here for more information about lamivudine This link exits the ClinicalTrials.gov site

Click here for more information about lopinavir/ritonavir This link exits the ClinicalTrials.gov site

Click here for more information about nelfinavir This link exits the ClinicalTrials.gov site

Click here for more information about nevirapine This link exits the ClinicalTrials.gov site

Click here for more information about zidovudine This link exits the ClinicalTrials.gov site

Click here for more information about starting anti-HIV medications This link exits the ClinicalTrials.gov site

Click here for more information about the HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT) This link exits the ClinicalTrials.gov site

Haga clic aquí para ver información sobre este ensayo clínico en español. This link exits the ClinicalTrials.gov site

Publications:

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. Epub 2007 Feb 12.

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. Epub 2002 Jan 8.

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. Epub 2007 Jan 9.

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.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

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.

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.

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.

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.

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.

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.


Responsible Party:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00234091 History of Changes
Other Study ID Numbers:	CIPRA TH001, PREDICT, 10409
Study First Received:	October 4, 2005
Last Updated:	December 2, 2013
Health Authority:	United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):


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

Additional relevant MeSH terms:


Acquired Immunodeficiency Syndrome Communicable Diseases HIV Infections Infection Immune System Diseases Immunologic Deficiency Syndromes Lentivirus Infections RNA Virus Infections Retroviridae Infections Sexually Transmitted Diseases Sexually Transmitted Diseases, Viral Slow Virus Diseases Virus Diseases Abacavir Efavirenz	Lamivudine Lopinavir Nelfinavir Nevirapine Ritonavir Zidovudine Anti-HIV Agents Anti-Infective Agents Anti-Retroviral Agents Antimetabolites Antiviral Agents Enzyme Inhibitors HIV Protease Inhibitors Molecular Mechanisms of Pharmacological Action Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on February 25, 2015

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