U.S. Updates Clinical Guidelines for Prevention & Treatment of Opportunistic Infections among HIV-Exposed & HIV-Infected Children

New guidelines to assist health care workers in preventing and treating the secondary infections that can afflict U.S. children exposed to, or infected with, HIV, were published by the National Institutes of Health and the Centers for Disease Control and Prevention.

The new guidelines provide a reference manual for the treatment of these secondary infections, describing warning signs of potentially hazardous interactions between drugs used to treat HIV and its secondary infections, current standards for treating the inflammation accompanying the immune system recovery made possible by new anti-HIV drugs, as well as when to discontinue preventative treatment no longer needed after the immune system has recovered.

HIV cripples the immune system, leaving infected people more vulnerable than the general population to numerous other infectious diseases. These diseases, which ordinarily do not cause problems for people with fully functioning immune systems, are known as opportunistic infections. HIV-associated opportunistic infections are a leading cause of hospitalization and death among HIV-infected children in the United States. Some of these opportunistic infections can also afflict children who do not have HIV but who have one or both parents with HIV and specific HIV-related opportunistic infections.

“The guidelines will help health care workers and public health officials who work with children to save lives that might otherwise be lost,” said Kathleen Sebelius, secretary of the U.S. Department of Health and Human Services.  “The infections that can accompany HIV are often the major cause of illness and death of HIV-infected children.”

The report, Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Exposed and HIV-Infected Children , updates recommendations on topics such as the importance of starting antiretroviral treatment early and interactions between drugs that treat HIV and drugs that treat opportunistic infections.

The report, the first update of the guidelines in five years, appears in the Sept. 4 issue of Morbidity and Mortality Weekly Report (MMWR).  The NIH and CDC produced the update in cooperation with the HIV Medicine Association of the Infectious Diseases Society of America, the American Academy of Pediatrics, and the Pediatric Infectious Disease Society.

The new guidelines apply to 23 opportunistic infectious diseases . A panel of more than 30 government and non-government pediatric HIV and infectious disease experts developed the guidelines. The guidelines update and combine two previous publications, a 2002 publication on the prevention of opportunistic infections in HIV-infected adults and children and a 2004 publication on the treatment of opportunistic infections in children.

In recent years, the number of HIV-associated opportunistic infections in children has declined significantly in the United States. The decrease is primarily due to advances in antiretroviral therapy. But the infections continue to occur, and they can be serious or even fatal.

“Health care providers must be vigilant for the signs and symptoms of these infections and know how to prevent and treat them,” said Lynne Mofenson, M.D., a coauthor of the new guidelines and chief of NICHD’s Pediatric, Adolescent, and Maternal AIDS Branch.

Because children’s immune systems are not as developed as adults, even children who do not have HIV may be at high risk of catching certain opportunistic infections, such as tuberculosis, if one or both parents have HIV and an accompanying opportunistic infection. Like HIV itself, some opportunistic infections, such as cytomegalovirus or hepatitis viruses, can be passed from mother to child.

“Guidelines for preventing and treating opportunistic infections in children must consider the risk of infections among both HIV-infected children and children who were HIV-exposed through birth to an HIV-infected mother." Dr. Mofenson said.

In recent years, HIV infection has increased among adolescents.

“We hope that doctors and clinicians make use of these new guidelines to ensure that adolescents with HIV are not severely impacted by other infections,” said Kenneth L. Dominguez, M.D., a coauthor of the new guidelines and epidemiologist at CDC's Divsion of HIV/AIDS Prevention.  “Despite our country's strong success in preventing perinatally HIV-infected infants, we must protect the significant numbers of current HIV-infected children and adolescents who are able to live longer, healthier lives due to advances in HIV therapy.”

Drug doses and response to treatment may differ for children or adolescents entering puberty than for adults. Guidelines for adults and postpubertal adolescents appear in another report, Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents, published in the April 10, 2009, issue of MMWR.

Major changes in the pediatric guidelines include:

  • Emphasis on the importance of effective antiretroviral therapy to improve children’s immune function.  The development of new therapies for HIV in children in recent years has shown that successful treatment of HIV itself is pivotal to preventing and controlling opportunistic infections.
  • Information on diagnosing and managing immune reconstitution inflammatory syndrome.  In this condition, the immune system begins to recover but then responds to a previously acquired opportunistic infection with an overwhelming response that worsens the symptoms of infection.  Despite the worsening symptoms, continuing antiretroviral treatment is critical, the guidelines say.
  • Information on the management of antiretroviral therapy in children with opportunistic infections, including potential drug-drug interactions.
  • New guidance on use of antibiotic drugs to prevent Pneumocystis jirovecii pneumonia in infants. Previously, doctors were advised to give an antibiotic to all infants born to HIV-infected mothers to prevent infection with Pneumocystis jiroveciipneumonia, starting at 4-6 weeks until the infant tested negative for HIV at 4-6 months of age or was found to be HIV-infected.  With advances in diagnostic testing and effective prevention of mother to child transmission, the new guidelines note that if infants have two negative tests for HIV at early timepoints (one at 2weeks or older and one at 4 weeks or older), use of antibiotics to prevent this infection may be avoided.
  • Updated immunization recommendations for HIV-exposed and -infected children, including hepatitis A, human papillomavirus, meningococcal, and rotavirus vaccines.
  • A new section outlining treatments for malaria, which may become an opportunistic infection in HIV-infected immigrant children or HIV-infected children who travel to countries with malaria.
  • New recommendations on when to discontinue medication for preventing opportunistic infections.  Previously, medications to prevent opportunistic infections were given for life.  Now, however, new therapies that inhibit HIV may allow the immune system to recover.  When the immune system has recovered sufficiently, the medications to prevent opportunistic infections may no longer be needed.  The guidelines list diagnostic criteria for discontinuing these medications.

The new guidelines (as well as all federal HIV prevention and treatment guidelines) appear on the AIDSinfo Web site, https://hivinfo.nih.gov/. Because treatment of opportunistic infections in children continues to evolve, NIH and CDC will update the recommendations as new treatments or clinical data on existing treatments become available.


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