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15 - Initiating and changing antiretroviral therapy
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- By Lynne M. Mofenson, Center for Research for Mothers and Children, National Institute of Child Health & Human Development, National Institutes of Health, Bethesda, MD, Leslie K. Serchuck, Center for Research for Mothers and Children, National Institute of Child Health & Human Development, National Institutes of Health, Bethesda, MD
- Edited by Steven L. Zeichner, National Cancer Institute, Bethesda, Maryland, Jennifer S. Read
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- Book:
- Handbook of Pediatric HIV Care
- Published online:
- 23 December 2009
- Print publication:
- 04 May 2006, pp 415-438
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- Chapter
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Summary
Introduction
Guidelines for antiretroviral therapy (ART) in children must incorporate certain unique considerations, including: age-related changes in drug pharmacokinetics; initiation of therapy during primary HIV infection; normal age-related changes in immunologic parameters; pediatric-specific features of the natural history of HIV infection (i.e., virologic parameters during primary infection, rapidity of disease progression, and frequency of central nervous system and growth abnormalities); prior antiretroviral (ARV) exposure of newborns (in utero and neonatal); and pediatric-specific adherence issues (i.e., availability and palatability of drug formulations; relationship of drug administration to food intake in infants; dependence on caregiver for drug administration).
Guidelines for treatment of HIV-infected children often rely on data regarding virologic/immunologic response to drug regimens in adult clinical trials, taking into account the specific considerations in pediatric HIV infection delineated above, and with attention to data from pediatric populations. Guidelines for pediatric ART have been developed in the USA and Europe, and by the World Health Organization. US pediatric ART guidelines [1], as well as adult guidelines (applicable to postpubertal adolescents) [2], are available at http://AIDSInfo.nih.gov. Guidelines for pediatric ART in Europe (http://www.ctu.mrc.ac.uk/PENTA) [3] and in resource-poor settings (http://www.who.int/hiv/pub/prev_care/en/ScalingUp_E.pdf) have been developed. The US pediatric guidelines for ART are the focus of this chapter, and the other guidelines are addressed only briefly. None of these guidelines is intended to supplant the clinical judgment of experienced clinicians. Whenever possible, HIV-infected children should be managed by, or in consultation with, a pediatric HIV specialist.
22 - Initiating and changing antiretroviral therapy
- from Part III - Antiretroviral therapy
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- By Lynne M. Mofenson, Chief, Pediatric, Adolescent and Maternal AIDS Branch, Center for Research for Mothers and Children, NIH, Rockville, MD, Leslie K. Serchuck, Medical Officer, Pediatric, Adolescent and Maternal AIDS Branch, Center for Research for Mothers and Children, NIH Rockville, MD
- Edited by Steven L. Zeichner, National Cancer Institute, Bethesda, Maryland, Jennifer S. Read, National Cancer Institute, Bethesda, Maryland
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- Book:
- Textbook of Pediatric HIV Care
- Published online:
- 03 February 2010
- Print publication:
- 28 April 2005, pp 355-376
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Summary
Introduction
Guidelines for antiretroviral therapy in children must incorporate considerations unique to pediatric HIV infection. Such considerations include: age-related changes in drug pharmacokinetics; issues related to diagnosis of perinatal infection (early diagnosis permits therapy to be initiated during primary HIV infection); normal age-related changes in immunologic parameters; differences between children and adults in the natural history of HIV infection (i.e. differences in virologic parameters during primary infection, in the rapidity of disease progression, and in the frequency of central nervous system (CNS) and growth abnormalities); prior antiretroviral exposure of newly infected infants (in utero and neonatal exposure to drugs used for maternal treatment and transmission prophylaxis); and pediatric-specific adherence issues (i.e. availability and palatability of drug formulations; relationship of drug administration to food intake in young infants; dependence on caregiver for administration of drugs).
Prospective, randomized, controlled clinical trials offer the best evidence for formulation of guidelines. However, most antiretroviral drugs are approved for use in pediatric patients based on efficacy data from clinical trials in adults, with supporting pharmacokinetic and safety data from phase I/II trials in children; additionally, efficacy in most adult trials has been based on surrogate marker data, as opposed to clinical endpoints. Thus, guidelines for treatment of HIV-infected children often have to rely on data regarding virologic/immunologic response to drug regimens in adult clinical trials, taking into account the specific considerations in pediatric HIV infection delineated above, and with attention to data from pediatric populations when available.
Early neurodevelopmental markers predictive of mortality in infants infected with HIV-1
- Antolin Llorente, Pim Brouwers, Manhattan Charurat, Laurence Magder, Kathleen Malee, Claude Mellins, Janice Ware, Joan Hittleman, Lynne Mofenson, Jesus Velez-Borras, Samuel Adeniyi-Jones
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- Journal:
- Developmental Medicine and Child Neurology / Volume 45 / Issue 2 / February 2003
- Published online by Cambridge University Press:
- 10 January 2003, pp. 76-84
- Print publication:
- February 2003
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- Article
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One-hundred and fifty-seven vertically infected HIV-1 positive infants (85 males, 72 females) underwent longitudinal assessment to determine whether early neurodevelopmental markers are useful predictors of mortality in those infants who survive to at least 4 months of age. Survival analysis methods were used to estimate time to death for quartiles of 4-month scores (baseline) on the Bayley Scales of Infant Development (BSID). Cox proportional hazards progression was used to estimate relative hazard (RH, 95% CI) of death for BSID scores and potential confounders. Thirty infants with BSID scores at 4 months of age died during follow-up. Survival analysis revealed greater mortality rates in infants with BSID (Mental Developmental Index and Psychomotor Developmental Index) scores in the lower quartile(p=0.004, p=0.036). Unadjusted univariate analyses revealed increased mortality associated with baseline CD4+ 29%, gestational age <37 weeks, smaller head circumference, advanced HIV and higher plasma viral load. BSID scores independently predicted mortality after adjusting for treatment, clinical category, gestational age, plasma viral load and CD4+ percentage.