Treatment Issues, Vol 11, No 7/8; July/August 1997
Karin Nielsen, Pediatric Infectious Disease Specialist, UCLA Maternal Child Clinic

Evaluating the Child's Status

Once it is clearly established that the child is infected with HIV, standard clinical and laboratory evaluations should be conducted. These include a complete physical exam with special attention to developmental assessment (growth, height and weight and central nervous system maturation). Key signs such as lymphadenopathy and enlargement of the spleen or liver should also be checked for. Lab tests should include T-cell subsets, complete blood count, quantitative immunoglobulins, and HIV viral load. If the child has any clinical findings of neurologic impairment, an MRI or CT scan of the brain and analysis of spinal fluid (by lumbar puncture) should occur. In an infant up to six months, urine should be tested for CMV, which may increase HIV viral load.

Combination Antiretroviral Therapy

Antiretroviral therapy in infants and children follows the same basic principles as treatment in adults. Monotherapy is out, combinations are in, protease inhibitors are good, and the goal is to treat early and treat effectively. Young patients with clinical signs and symptoms of HIV disease or an AIDS-defining condition should receive antiretroviral therapy. Some clinicians favor the approach of initiating combination therapy immediately in all HIV-infected children, regardless of age or symptom status in order to prevent immune system deterioration.

Of the currently available HIV drugs marketed for adults, eight have been approved for children: AZT, ddI, d4T, 3TC, ddC, ritonavir, nelfinavir and nevirapine. Most of these drugs are available in pediatric formulations, although the preparations for nevirapine and ddC are still investigational (most children under six cannot swallow pills). Common combinations used in pediatric patients are shown in Table 1.

Side effects in children are common but do not differ significantly from those in adults. However, since HIV-infected children may already be underweight, GI disturbances such as anorexia, alteration of taste, nausea, vomiting and diarrhea can be especially difficult for parents, children and clinicians to accept. As with adults, protease inhibitors require continuous adherence to the drug regimen.

Viral load, immune function, drug tolerance and clinical status guide changes in antiretroviral therapy. Most clinicians agree that certain signs are indicative of treatment failure. These include new symptoms characteristic of HIV disease, growth failure, development of neurologic problems, loss of previously gained milestones (such as talking, walking, social skills), loss of CD4 cells and a significant increase in viral load.

Conversely, with effective treatment, dramatic response to therapy may occur, including functional improvements, weight gain, shrinking of lymph nodes, spleen and liver. Children who have a history of neurologic disease and are frequently sluggish and cannot walk and/or talk, often start sitting up and talking. Brain atrophy, as observed on an MRI, may even be reversed, if caught early enough. Because of these clinical impressions, many HIV pediatric specialists believe in treating as early as possible.

Opportunistic Conditions

In addition to antiretroviral therapy, children with HIV infection require surveillance, prevention and treatment of other infections and HIV-associated conditions. PCP prophylaxis is critical for infected children. Children have different absolute CD4 count values than adults; therefore, indications for PCP prophylaxis in children differ (see Table 2 for guidelines).

Approximately 20% of children with HIV infection develop recurrent, serious bacterial infections (pneumonia, meningitis) and a large proportion of children have recurrent mild infections such as otitis media, sinusitis, or impetigo. Many of these children have deficient antibody production and/or function and benefit from monthly infusions of intravenous immunoglobulins (IVIG). Another common problem in pediatric HIV infection is recurrent oral thrush that can progress to invasive candida esophagitis. Treatment and prophylaxis is similar to adults.

In addition, children with HIV infection are at risk for more severe varicella (chickenpox) or recurrent varicella syndrome (recurrent chickenpox). Prophylaxis of an initial exposure in children who have never had chickenpox is by varicella zoster immunoglobulin (VZIG) which should be given within three days of exposure to the contact case. If an HIV-infected child develops varicella, she/he should be treated with either oral or intravenous acyclovir, depending on disease severity. For resistant varicella, foscarnet is another treatment option, and valaciclovir is presently under investigation.

Children with advanced HIV disease are at risk for CMV, MAC and TB. CMV may be a complication of late stage disease and might also be a cofactor in disease progression. Prophylaxis of MAC is indicated for children with CD4 counts under 100 (or <15%), and can be accomplished with rifabutin, clarithromycin or azithromycin. Incidence rates of TB in HIV-infected infants who are exposed to a TB-infected individual are 10-to 100-fold greater than in the general population. Children and family members should be screened annually with PPD skin testing, and chest X-rays when appropriate.

Lymphoid interstitial pneumonitis (LIP), a chronic pulmonary disease, has been classified as the second most common manifestation in HIV-positive children. Unlike PCP, LIP is rarely fatal and can be treated with bronchodilators (inhalers).

Children with HIV infection should follow a slightly different vaccination schedule in order to avoid exposure to any live vaccines. Oral polio vaccine and varicella zoster vaccine are contraindicated in HIV pediatric patients (and family members living in the same household). Children infected with HIV can receive IPV (inactivated polio vaccine). MMR (measles, mumps, rubella) vaccine should not be given to severely immune-compromised children. HIV-infected children should receive pneumococcal vaccine as well as yearly influenza vaccine after two years of age. The other childhood immunizations (hepatitis B, DPT (diphteria-tetanus-pertussis), and Haemophilus influenza vaccine (HIB) should be given according to routine childhood immunization schedules.

Table 1

AZT and 3TC d4T and 3TC AZT and ddI d4T and ddI AZT and ddC (with a protease inhibitor, usually ritonavir or nelfinavir:)

Table 2*

Age CD4 Count CD4%

<1 year <1500 <30%

1-2 years <750 <25%

2-6 years <500 <20%

>6 years <200 <20%

*This table reflects the practice at UCLA. In April 1995, the CDC issued guidelines recommending PCP prophylaxis for all children between 6 weeks and 12 months old who are infected or possibly infected with HIV. From one to five years, PCP prophylaxis should continue if the CD4 count is less than 500 or the CD4 percentage is below 15%. For children older than six years, the CDC thresholds are a CD4 count of 200 or a CD4 percentage of 15%.

970701
GM110716

Copyright © 1997 - Treatment Issues. Reproduced with permission. Treatment Issues is published twelve times yearly by GMHC, Inc. All rights reserved. Noncommercial reproduction is encouraged. Subscription lists are kept confidential. GMHC Treatment Issues, The Tisch Building, 119 West 24th Street, New York, NY 10011  fredg@gmhc.org  http://www.gmhc.org

AEGiS is made possible through unrestricted grants from Boehringer Ingelheim, Elton John AIDS Foundation, iMetrikus, Inc., John M. Lloyd Foundation, the National Library of Medicine, and donations from users like you. Always watch for outdated information. This article first appeared in 2003. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 2003. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .