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Unresolved Antiretroviral Treatment Management Issues in HIV-Infected Children

Heidari, Shirin PhD*; Mofenson, Lynne M. MD; Hobbs, Charlotte V. MD; Cotton, Mark F. FCPaed, PhD§; Marlink, Richard MD‖,¶; Katabira, Elly MD#

JAIDS Journal of Acquired Immune Deficiency Syndromes: February 1st, 2012 - Volume 59 - Issue 2 - p 161–169
doi: 10.1097/QAI.0b013e3182427029
Critical Review: Clinical Science

Abstract: Antiretroviral therapy in children has expanded dramatically in low-income and middle-income countries. The World Health Organization revised its pediatric HIV guidelines to recommend initiation of antiretroviral therapy in all HIV-infected children younger than 2 years, regardless of CD4 count or clinical stage. The number of children starting life-long antiretroviral therapy should therefore expand dramatically over time. The early initiation of antiretroviral therapy has indisputable benefits for children, but there is a paucity of definitive information on the potential adverse effects. In this review, a comprehensive literature search was conducted to provide an overview of our knowledge about the complications of treating pediatric HIV.

Antiretroviral therapy in children, as in adults, is associated with enhanced survival, reduction in opportunistic infections, improved growth and neurocognitive function, and better quality of life. Despite antiretroviral therapy, HIV-infected children may continue to lag behind their uninfected peers in growth and development. In addition, epidemic concurrent conditions, such as tuberculosis, malaria, and malnutrition, can combine with HIV to yield more rapid disease progression and poor treatment outcomes.

Additional studies are required to evaluate the long-term effects of antiretroviral therapy in HIV-infected infants, children, and adolescents, particularly in resource-limited countries where concomitant infections and conditions may enhance the risk of adverse effects. There is an urgent need to evaluate drug–drug interactions in children to determine optimal treatment regimens for both HIV and coinfections.

*Department of Research Promotion, International AIDS Society, Geneva, Switzerland

Pediatric, Adolescent and Maternal AIDS Branch, Eunice Kennedy Shriver, National Institutes of Health, Bethesda, MD

Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Disease, National Institutes of Health, Rockville, MD

§Department of Pediatrics and Child Health, Stellenbosch University and Tygerberg Children's Hospital, South Africa

Harvard School of Public Health, Boston, MA

Elizabeth Glaser Pediatric AIDS Foundation, Los Angeles, CA

#Makerere University College of Health Sciences, Kampala, Uganda.

Correspondence to: Shirin Heidari, PhD, International AIDS Society, 71 Ave Louis-Casai, 1216 Cointrin, Geneva, Switzerland (e-mail:

The mapping exercise was financially supported by unrestricted educational grants from Abbott, Boehringer Ingelheim, Gilead, Merck, Pfizer, Tibotec and ViiV Healthcare, and the International AIDS Society.

The authors S.H. is an employee of the International AIDS Society, and her salary is provided partly by unrestricted educational grants from the following pharmaceutical companies: Abbott, Boehringer Ingelheim, Gilead, Merck, Pfizer, Tibotec and ViiV Healthcare. M.F.C. is an investigator on GSK and Boehringer Ingelheim trials and has received honoraria from Abbott and GSK within the past 6 months. R.M. has served as an advisor to the BMS Foundation and the Merck Company Foundation. L.M.M., C.V.H., and E.K. have no competing interests.

The conclusions and opinions expressed in this article are those of the authors and do not necessarily reflect those of their respective organizations, including the National Institutes of Health or the US Department of Health and Human Services.

Authors contributions—S.H., with the support of medical writer David Gilden, wrote the initial draft. C.H. provided expert advice and substantially revised the section on malaria. L.M. contributed substantially to the manuscript by providing extensive comments. All other authors contributed equally by providing expert comments. All authors have read and approved the final version.

Received May 17, 2011

Accepted November 16, 2011

© 2012 Lippincott Williams & Wilkins, Inc.