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Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Exposed and HIV-Infected Children

Summary

(Last updated: November 6, 2013; last reviewed: November 6, 2013)

This report updates the last version of the Guidelines for the Prevention and Treatment of Opportunistic Infections (OIs) in HIV-Exposed and HIV-Infected Children, published in 2009. These guidelines are intended for use by clinicians and other health-care workers providing medical care for HIV-exposed and HIV-infected children in the United States. The guidelines discuss opportunistic pathogens that occur in the United States and ones that might be acquired during international travel, such as malaria. Topic areas covered for each OI include a brief description of the epidemiology, clinical presentation, and diagnosis of the OI in children; prevention of exposure; prevention of first episode of disease; discontinuation of primary prophylaxis after immune reconstitution; treatment of disease; monitoring for adverse effects during treatment, including immune reconstitution inflammatory syndrome (IRIS); management of treatment failure; prevention of disease recurrence; and discontinuation of secondary prophylaxis after immune reconstitution. A separate document providing recommendations for prevention and treatment of OIs among HIV-infected adults and post-pubertal adolescents (Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents) was prepared by a panel of adult HIV and infectious disease specialists (see http://aidsinfo.nih.gov/guidelines).

These guidelines were developed by a panel of specialists in pediatric HIV infection and infectious diseases (the Panel on Opportunistic Infections in HIV-Exposed and HIV-Infected Children) from the U.S. government and academic institutions. For each OI, one or more pediatric specialists with subject-matter expertise reviewed the literature for new information since the last guidelines were published and then proposed revised recommendations for review by the full Panel. After these reviews and discussions, the guidelines underwent further revision, with review and approval by the Panel, and final endorsement by the National Institutes of Health (NIH), Centers for Disease Control and Prevention (CDC), the HIV Medicine Association (HIVMA) of the Infectious Diseases Society of America (IDSA), the Pediatric Infectious Disease Society (PIDS), and the American Academy of Pediatrics (AAP). So that readers can ascertain how best to apply the recommendations in their practice environments, the recommendations are rated by a letter that indicates the strength of the recommendation, a Roman numeral that indicates the quality of the evidence supporting the recommendation, and where applicable, a * notation that signifies a hybrid of higher-quality adult study evidence and consistent but lower-quality pediatric study evidence. 

More detailed methodologic considerations are listed in Appendix 1 (Important Guidelines Considerations), including a description of the make-up and organizational structure of the Panel, definition of financial disclosure and management of conflict of interest, funding sources for the guidelines, methods of collecting and synthesizing evidence and formulating recommendations, public commentary, and plans for updating the guidelines. The names and financial disclosures for each of the Panel members are listed in Appendices 2 and 3, respectively. 

An important mode of childhood acquisition of OIs and HIV infection is from infected mothers. HIV-infected women may be more likely to have coinfections with opportunistic pathogens (e.g., hepatitis C) and more likely than women who are not HIV-infected to transmit these infections to their infants. In addition, HIV-infected women or HIV-infected family members coinfected with certain opportunistic pathogens may be more likely to transmit these infections horizontally to their children, resulting in increased likelihood of primary acquisition of such infections in young children. Furthermore, transplacental transfer of antibodies that protect infants against serious infections may be lower in HIV-infected women than in women who are HIV-uninfected. Therefore, infections with opportunistic pathogens may affect not just HIV-infected infants but also HIV-exposed, uninfected infants. These guidelines for treating OIs in children, therefore, consider treatment of infections in all children—HIV-infected and HIV-uninfected—born to HIV-infected women.

In addition, HIV infection increasingly is seen in adolescents with perinatal infection who are now surviving into their teens and in youth with behaviorally acquired HIV infection. Guidelines for postpubertal adolescents can be found in the adult OI guidelines, but drug pharmacokinetics (PK) and response to treatment may differ in younger prepubertal or pubertal adolescents. Therefore, these guidelines also apply to treatment of HIV-infected youth who have not yet completed pubertal development.

Major changes in the guidelines from the previous version in 2009 include: 

  • Greater emphasis on the importance of antiretroviral therapy (ART) for prevention and treatment of OIs, especially those OIs for which no specific therapy exists;
  • Increased information about diagnosis and management of IRIS; 
  • Information about managing ART in children with OIs, including potential drug-drug interactions; 
  • Updated immunization recommendations for HIV-exposed and HIV-infected children, including pneumococcal, human papillomavirus, meningococcal, and rotavirus vaccines; 
  • Addition of sections on influenza, giardiasis, and isosporiasis;
  • Elimination of sections on aspergillosis, bartonellosis, and HHV-6 and HHV-7 infections; and 
  • Updated recommendations on discontinuation of OI prophylaxis after immune reconstitution in children. 

The most important recommendations are highlighted in boxed major recommendations preceding each section, and a table of dosing recommendations appears at the end of each section. The guidelines conclude with summary tables that display dosing recommendations for all of the conditions, drug toxicities and drug interactions, and 2 figures describing immunization recommendations for children aged 0 to 6 years and 7 to 18 years.

The terminology for describing use of antiretroviral (ARV) drugs for treatment of HIV infection has been standardized to ensure consistency within the sections of these guidelines and with the Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection. Combination antiretroviral therapy (cART) indicates use of multiple (generally 3 or more) ARV drugs as part of an HIV treatment regimen that is designed to achieve virologic suppression; highly active antiretroviral therapy (HAART), synonymous with cART, is no longer used and has been replaced by cART; the term ART has been used when referring to use of ARV drugs for HIV treatment more generally, including (mostly historical) use of one- or two-agent ARV regimens that do not meet criteria for cART.

Because treatment of OIs is an evolving science, and availability of new agents or clinical data on existing agents may change therapeutic options and preferences, these recommendations will be periodically updated and will be available at http://AIDSinfo.nih.gov.

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