INTRODUCTION
In 1993, the Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children, composed of specialists caring for human immunodeficiency virus (HIV)-infected infants, children, and adolescents, was convened by the National Pediatric and Family HIV Resource Center (NPHRC). On the basis of available data and a consensus reflecting clinical experience, the Working Group concluded that antiretroviral therapy was indicated for any child with a definitive diagnosis of HIV infection who had evidence of substantial immunodeficiency (based on age-related CD4+ T-lymphocyte count thresholds) and/or who had HIV-associated symptoms. Zidovudine (ZDV) monotherapy was recommended as the standard of care for initiation of therapy. Routine antiretroviral therapy for infected children who were asymptomatic or had only minimal symptoms (e.g., isolated lymphadenopathy or hepatomegaly) and normal immune status was not recommended (1).
Since the Working Group developed the 1993 recommendations, dramatic advances in laboratory and clinical research have been made. The rapidity and magnitude of HIV replication during all stages of infection are greater than previously believed and account for the emergence of drug-resistant viral variants when antiretroviral treatment does not maximally suppress replication (2,3). New assays that quantitate plasma HIV RNA copy number have become available, permitting a sensitive assessment of risk for disease progression and adequacy of antiretroviral therapy. A new class of antiretroviral drugs, protease inhibitors, has become available; these agents have reduced HIV viral load to levels that are undetectable and have reduced disease progression and mortality in many HIV-infected persons. Therefore, therapeutic strategies now focus on early institution of antiretroviral regimens capable of maximally suppressing viral replication to reduce the development of resistance and to preserve immunologic function. Additionally, the results of Pediatric AIDS Clinical Trials Group (PACTG) protocol 076 have demonstrated that the risk for perinatal HIV transmission can be substantially diminished with the use of a regimen of ZDV administered during pregnancy, during labor, and to the newborn (4).These advances in HIV research have led to major changes in the treatment and monitoring of HIV infection in the United States. A summary of the basic principles underlying therapy of HIV-infected persons has been formulated by the National Institutes of Health (NIH) Panel to Define Principles of Therapy of HIV Infection (5). Treatment recommendations for infected adults and post-pubertal adolescents have been developed by the U.S. Department of Health and Human Services Panel of Clinical Practices for Treatment of HIV Infection (5).
Although the pathogenesis of HIV infection and the general virologic and immunologic principles underlying the use of antiretroviral therapy are similar for all HIV-infected persons, there are unique considerations needed for HIV-infected infants, children, and adolescents. Most HIV infections in children are acquired perinatally, and most perinatal transmission occurs during or near the time of birth, which raises the possibility of initiating treatment in an infected infant during the period of initial (e.g., primary) HIV infection (if sensitive diagnostic tests are used to define the infants infection status early in life). Perinatal HIV infection occurs during the development of the infants immune system; thus, both the clinical manifestations of HIV infection and the course of immunologic and virologic markers of infection differ from those for adults. Treatment of perinatally infected children will occur in the context of prior exposure to ZDV and other antiretroviral drugs used during pregnancy and the neonatal period, either for maternal treatment, to prevent perinatal transmission, or both (6,7). Additionally, drug pharmacokinetics change during the transition from the newborn period to adulthood, requiring specific evaluation of drug dosing and toxicity in infants and children. Finally, optimizing adherence to therapy in children and adolescents requires specific considerations.
To update the 1993 antiretroviral treatment guidelines for children and to provide guidelines for antiretroviral treatment similar to those for HIV-infected adults (5), NPHRC, the Health Resources and Services Administration, and NIH reconvened the Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children, consisting of experts caring for HIV-infected children and adolescents, family members of HIV-infected children, and government agency representatives. The Working Group met in June 1996 and again in July 1997 to establish and finalize new guidelines for the treatment of HIV-infected infants, children, and adolescents.
The treatment recommendations provided in this report are based on published and unpublished data regarding the treatment of HIV infection in adults and children and, when no definitive data were available, the clinical experience of the Working Group members. The Working Group intended the guidelines to be flexible and not to supplant the clinical judgement of experienced healthcare providers. These guidelines will need to be modified as new information and clinical experience become available.
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