Appropriate antiretroviral therapy and treatment of specific infections and malignancies are critical in treating patients who are HIV positive. Intervening early may prevent damage to the immune system and potentially retard infection dissemination. The reverse transcriptase inhibitors are composed of the dideoxynucleosides and the nonnucleoside reverse transcriptase inhibitors (NRTIs). By inhibiting viral reverse transcriptase, HIV replication is suppressed. Protease inhibitors (PIs) prevent the late stages of viral replication by interfering with the formation of structural proteins of the virion core. Combination antiretroviral therapy is recommended for all infants, children, and adolescents.
The following are the 2006 Working Group goals for treating pediatric patients with HIV infection:
- Reducing HIV-related mortality and morbidity
- Restoring and preserving immune function
- Maximally and durably suppressing viral replication
- Minimizing drug-related toxicity
- Maintaining normal physical growth and neurocognitive development
- Improving quality of life
The following are several important factors to consider in making treatment decisions about when to initiate antiretroviral therapy:
· Severity of HIV disease
· Risk of disease progression
· Laboratory assessments (eg, CD4+ count, plasma HIV RNA levels)
· Availability of appropriate and palatable drug formulations
· Adverse effects of the antiretroviral medications
· Effect of initial treatment regimen choice on later therapeutic options
· Presence of comorbidities that may affect drug choices
· Potential antiretroviral drug interactions with required concomitant medications
· Ability of the child and caregiver to adhere to treatment regimen
A high prevalence of infections, such as candidiasis and varicella-zoster virus infection, must be anticipated, and appropriate prevention and treatment strategies must be initiated.
As the disease progresses, wasting is noted, with weight loss and growth retardation in children. Low protein stores can be countered by increasing the intake of amino acids, specifically threonine and methionine.
Address abnormalities in psychological and neurologic development, due, in part, to the tropism of the virus for CNS tissue in children who are HIV positive.
Surgical intervention is needed if an underlying neoplasm exists or intervention (eg, feeding tube) is indicated.
- Consult a pediatric HIV specialist to assist in the treatment of children with HIV disease.
- Appropriate specialty referrals for evaluation are warranted and include an audiologist, an ophthalmologist, a dentist, and a neurodevelopmental specialist (see Other Tests).
- Initiate oral supplementation with increased energy intake as high as 150% of the US recommended daily allowance for calories and protein when nutritional deficits are identified.
- If necessary, enteral supplementation with tube feedings may be warranted.
- Pay special attention to protein deficits.
- Some studies have shown that appetite stimulants, such as megestrol acetate and human recombinant growth hormone, can improve growth and weight.
The Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children established treatment recommendations categorized by age.
Children younger than 12 months
The group recommends initiating antiretroviral treatment in all infants younger than 12 months who have clinical or immunologic symptoms of HIV infection, regardless of HIV RNA level. It also recommends therapy in asymptomatic infants younger than 12 months with a CD4 count of less than 25%. It recommends considering therapy in those younger than 12 months who are asymptomatic with a normal immune status.
Children aged 1-4 years
The Working Group recommends treating all children aged 1-4 years who have AIDS or significant HIV-related symptoms and for patients who are asymptomatic or have mild symptoms and a CD4 of less than 20%. It recommends considering treatment in patients who are asymptomatic or have mild symptoms and CD4 levels of 20-24% or with HIV RNA levels greater than or equal to 100,000 copies/mL. It recommends deferring treatment in asymptomatic patients and in those with CD4 counts greater than 25% and HIV RNA levels less than or equal to 100,000 copies/mL.
Children aged 4-12 years
The Working Group recommends treating all children age 4-12 years who have AIDS or significant HIV-related symptoms and for patients who are asymptomatic or have mild symptoms and a CD4 level of less than 15%. It recommends considering treatment in patients who are asymptomatic or have mild symptoms and CD4 levels of 15-24% or with HIV RNA levels greater than or equal to 100,000 copies/mL. It recommends deferring treatment in asymptomatic patients and in those with CD4 levels greater than 25% and HIV RNA levels less than or equal to 100,000 copies/mL.
Children 13 years or older
The Working Group recommends treating all children older than 13 years who have AIDS or significant HIV-related symptoms and for patients who are asymptomatic or have mild symptoms and a CD4 count less than 200 cells/mL. It recommends considering treatment in patients who are asymptomatic or have mild symptoms and CD4 counts of 201-350 cells/mL or with HIV RNA levels greater than or equal to 100,000 copies/mL. It recommends deferring treatment in asymptomatic patients and in those with CD4 counts greater than 350 cells/mL and HIV RNA levels less than or equal to 100,000 copies/mL.
Some pediatric HIV experts recommend that all children younger than 1 year be treated empirically, even if they are considered to be immunocompetent. Other specialists believe that treatment should be postponed until the immune status deteriorates or CD4+ counts decrease. Given that the risk of disease progression is slower in children older than 1 year, treatment deferment may be considered for older children. Although in adults the goal of therapy is to achieve undetectable levels of HIV RNA, in children only a reduction in the numbers of HIV RNA copies may be seen.
When treating older children, some advocate considering a child’s Tanner stage when determining dosing regimens. Adolescents in early puberty (Tanner stages I and II) should be treated according to pediatric dosing guidelines. Adolescents in late puberty (Tanner stage IV) and postpubertal adolescents should follow adult dosing guidelines.
The 2006 Working Group generally preferred recommendation for children includes a combination antiretroviral regimen in previously untreated children with 1 non-NRTI (NNRTI) or 1 PI combined with a 2-drug NRTI combination. It recommends using a 3-drug NRTI regimen only when an NNRTI or a PI cannot be used.
For children younger than 3 years or for children who cannot swallow tablets, the preferred NNRTI-based treatment recommendations include 2 NRTIs plus nevirapine. For children 3 years and older, it is 2 NRTIs plus efavirenz. Nevirapine may be used as an alternative for efavirenz for children 3 years or older.
The preferred PI-based regimen for children is 2 NRTIs plus lopinavir/ritonavir. The alternate recommendation for children older than 2 years is 2 NRTIs plus nelfinavir.
Currently, no nucleoside analogue–based regimen is strongly recommended. Two-drug NRTI regimens may be used in combination with additional agents. The preferred combination is zidovudine plus lamivudine, didanosine, or emtricitabine. A second preferred combination is didanosine plus lamivudine or emtricitabine. An alternative nucleoside analogue–based regimen is abacavir plus zidovudine, lamivudine, emtricitabine, or stavudine.
The following antiretroviral regimens are generally not recommended and should only be considered in unique exceptions: monotherapy, 2 NRTIs alone, tenofovir plus abacavir plus lamivudine or emtricitabine as a triple-NRTI regimen, tenofovir plus didanosine plus lamivudine or emtricitabine as a triple-NRTI regimen.
Several considerations have been established to guide clinicians regarding when to make changes in an antiretroviral regimen. Virologic considerations include inadequate response after 8-12 weeks or unsuppressed HIV RNA levels after 4-6 months. Viral rebound is another virologic consideration for changing antiretroviral therapy, as is demonstrated by (1) repeated detection of HIV RNA levels of greater than 400 copies/mL when previously undetectable or (2) a greater than 3-fold increase in HIV RNA copy number for children 2 years or older or a greater than 5-fold increase for children younger than 2 years.
Immunologic considerations that warrant a change in antiretrovirals includes a change in immunologic classification, persistent CD4+ declines, or a rapid decrease in absolute CD4+ T-cell count.
Incomplete immunologic response to therapy is likely in children with severe immune suppression who have not improved their CD4 percentage by at least 5 percentage points. The 2006 Working Group also classifies children aged 4-6 years who do not increase their CD4 count by 50 cell/mL above baseline as incomplete immunologic responders. The Working Group also states that a persistent immunologic decline of 5 percentage points or decline to below pretreatment CD4 absolute counts in children aged 4-6 years may also warrant an antiretroviral therapy change.
Clinical considerations include neurodevelopmental deterioration, growth failure, severe or recurrent infection or illness, and an adverse change in clinical category status.
Other drugs, as appropriate for specific infections or malignancies, are required. More specifically, P carinii pneumonia prophylaxis is recommended in patients who are HIV positive and younger than 1 year and in older children based on CD4+ counts.
- Kline MW. Pediatric HIV Infection. Baylor International Pediatric AIDS Initiative–Educational Resources. 2005.
- Kovacs A, Scott GB. Advances in the management and care of HIV-positive newborns and infants. In: Pizzo PA, Wilfert CM. Pediatric AIDS: The Challenge of HIV Infection in Infants, Children, and Adolescents. 3rd ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 1998:567-92.
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