Guidelines for Opportunistic Infections in Children With HIV
This executive report provides an overview of the 2013 update of the Department of Health and Human Services (DHHS) Guidelines for the Prevention and Treatment of Opportunistic Infections (OIs) in HIV-Exposed and HIV-Infected Children in the United States. The full text of the guidelines is available online at www.aidsinfo.nih.gov and as a supplement to the Pediatric Infectious Disease Journal. 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. A separate document providing recommendations for prevention and treatment of OIs among HIV-infected adults and postpubertal adolescents (Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents) was prepared by a working group of adult HIV and infectious disease specialists and is also available at www.aidsinfo.nih.gov.
The 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 US government and academic institutions, under the auspices of the National Institutes of Health (NIH) Office for AIDS Research. For each OI, 1 or more pediatric specialists with subject-matter expertize reviewed the literature for new information since the last guidelines were published (2009) 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, followed by review by the Centers for Disease Control and Prevention (CDC) subject matter experts and final review and endorsement by NIH, CDC, the HIV Medicine Association of the Infectious Diseases Society of America, the Pediatric Infectious Disease Society and the American Academy of Pediatrics. Treatment of OIs is an evolving science, and availability of new agents or clinical data on existing agents may change therapeutic options and preferences. As a result, these recommendations will need to be periodically updated. Interim updates to recommendations will be posted on the www.aids.nih.gov website as needed and the full guidelines document will continue to be reviewed and updated every 2–3 years. Consultation with an expert in the management of HIV infection and OIs in children is also encouraged.
Major recommendations are accompanied by ratings that include a letter that indicates the strength of the recommendation and a Roman numeral that indicates the quality of the evidence supporting the recommendation (Table 1); this rating system is similar to the rating systems used in other United States Public Health Service (USPHS)/Infectious Diseases Society of America guidelines. Because licensure of drugs for children and their application in clinical care often rely on efficacy data from adult trials in combination with pharmacokinetic, safety and observational data in children, recommendations sometimes rely on data from clinical trials or studies in adults with supporting data in children. Thus, the quality of evidence level is accompanied by an asterisk (*) to indicate that evidence supporting the recommendation is a hybrid of higher quality adult study evidence and consistent but lower quality pediatric study evidence. This modification to the rating system is the same as that used by the DHHS Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection.
The guidelines discuss opportunistic illnesses that occur in the United States and ones that might occur during international travel, such as malaria. Because the guidelines target HIV-exposed and -infected children in the United States, the opportunistic pathogens discussed are those common to the United States and do not include certain pathogens such as Penicillium marneffei that may be seen almost exclusively outside the United States. They also do not include pathogens that are common but seldom cause chronic infection or that have the same risk, disease course and approach to prevention and treatment in all children regardless of HIV status. 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. The most important rated recommendations are highlighted in boxed major recommendations sections preceding the text for each OI, and a table of dosing recommendations follows the text for each OI. The tables at the end of the document summarize recommendations for dosing of medications used for prevention and treatment of OIs in children; drug preparation and toxicity information for children and major drug-drug interactions. Vaccination recommendations for HIV-infected children and adolescents are summarized in the section entitled "Preventing Vaccine-Preventable Diseases in HIV-Infected Children and Adolescents" and individual OI sections and detailed in figures at the end of the document.
Introduction
This executive report provides an overview of the 2013 update of the Department of Health and Human Services (DHHS) Guidelines for the Prevention and Treatment of Opportunistic Infections (OIs) in HIV-Exposed and HIV-Infected Children in the United States. The full text of the guidelines is available online at www.aidsinfo.nih.gov and as a supplement to the Pediatric Infectious Disease Journal. 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. A separate document providing recommendations for prevention and treatment of OIs among HIV-infected adults and postpubertal adolescents (Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents) was prepared by a working group of adult HIV and infectious disease specialists and is also available at www.aidsinfo.nih.gov.
The 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 US government and academic institutions, under the auspices of the National Institutes of Health (NIH) Office for AIDS Research. For each OI, 1 or more pediatric specialists with subject-matter expertize reviewed the literature for new information since the last guidelines were published (2009) 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, followed by review by the Centers for Disease Control and Prevention (CDC) subject matter experts and final review and endorsement by NIH, CDC, the HIV Medicine Association of the Infectious Diseases Society of America, the Pediatric Infectious Disease Society and the American Academy of Pediatrics. Treatment of OIs is an evolving science, and availability of new agents or clinical data on existing agents may change therapeutic options and preferences. As a result, these recommendations will need to be periodically updated. Interim updates to recommendations will be posted on the www.aids.nih.gov website as needed and the full guidelines document will continue to be reviewed and updated every 2–3 years. Consultation with an expert in the management of HIV infection and OIs in children is also encouraged.
Major recommendations are accompanied by ratings that include a letter that indicates the strength of the recommendation and a Roman numeral that indicates the quality of the evidence supporting the recommendation (Table 1); this rating system is similar to the rating systems used in other United States Public Health Service (USPHS)/Infectious Diseases Society of America guidelines. Because licensure of drugs for children and their application in clinical care often rely on efficacy data from adult trials in combination with pharmacokinetic, safety and observational data in children, recommendations sometimes rely on data from clinical trials or studies in adults with supporting data in children. Thus, the quality of evidence level is accompanied by an asterisk (*) to indicate that evidence supporting the recommendation is a hybrid of higher quality adult study evidence and consistent but lower quality pediatric study evidence. This modification to the rating system is the same as that used by the DHHS Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection.
The guidelines discuss opportunistic illnesses that occur in the United States and ones that might occur during international travel, such as malaria. Because the guidelines target HIV-exposed and -infected children in the United States, the opportunistic pathogens discussed are those common to the United States and do not include certain pathogens such as Penicillium marneffei that may be seen almost exclusively outside the United States. They also do not include pathogens that are common but seldom cause chronic infection or that have the same risk, disease course and approach to prevention and treatment in all children regardless of HIV status. 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. The most important rated recommendations are highlighted in boxed major recommendations sections preceding the text for each OI, and a table of dosing recommendations follows the text for each OI. The tables at the end of the document summarize recommendations for dosing of medications used for prevention and treatment of OIs in children; drug preparation and toxicity information for children and major drug-drug interactions. Vaccination recommendations for HIV-infected children and adolescents are summarized in the section entitled "Preventing Vaccine-Preventable Diseases in HIV-Infected Children and Adolescents" and individual OI sections and detailed in figures at the end of the document.