Human immunodeficiency virus (HIV)-infected infants or children should be treated by pediatric HIV Specialists. When this is not possible, the treating clinician should seek consultation with a pediatric HIV Specialist (refer HIV Specialist Policy in the "Availability of Companion Documents" field).
The following clinical care issues are unique to HIV-infected children:
- Age-related differences in virologic, immunologic, and pharmacokinetic parameters
- Differences in tolerability and palatability of pediatric formulations of the medications
- Obstacles associated with adherence to complex regimens
- The dynamics of working with a family unit rather than a single individual
Assessment of the HIV-Infected Infant or Child Before Initiating Antiretroviral (ARV) Therapy
When a child is identified as HIV-infected, the clinician should begin an immediate assessment of the child's clinical and immunologic status, viral burden, resistance profile, and ability to adhere to an ARV regimen. This assessment should be repeated at least every 3 to 4 months to monitor for changes that may necessitate initiating ARV therapy or may affect a child's ability to receive or tolerate ARV therapy.
Before initiating therapy, clinicians should perform a comprehensive physical examination and should obtain a complete history and the following laboratory evaluations:
- Complete blood count (CBC)
- Assessment of kidney and hepatic function
- Amylase, lipase, glucose, and lipid profile (total cholesterol, high-density lipoprotein [HDL], low-density lipoprotein [LDL], and triglycerides)
- Viral load
- CD4 count and percentage
- Resistance profile
Immunological Status
Clinicians should obtain an assessment of lymphocyte subsets (absolute count and percentage) for HIV-infected infants and children.
Viral Load
Clinicians should obtain a baseline measurement of plasma HIV-1 ribonucleic acid (RNA) copy number (viral load) for all HIV-infected infants and children.
Clinicians should use one assay consistently in a patient because there is significant interassay variability.
Genotypic/Phenotypic Resistance Testing
Clinicians should obtain resistance testing before initiating treatment in ARV-naïve infants, children, and adolescents or changing a failing regimen for patients already receiving treatment.
Clinicians should consult with an expert for interpretation of resistance testing results.
Potential Barriers to Treatment Adherence
Clinicians should identify and address potential barriers to adherence with caregivers and patients before initiating a regimen.
The clinician should discuss the importance of consistent adherence to the ARV regimen with the child in an age-appropriate way.
If adherence barriers cannot be overcome, the clinician and family may choose to defer treatment.
The following potential barriers should be assessed and addressed before initiating ARV therapy:
- Communication difficulties due to language, literacy, or differing beliefs
- Unstable living conditions (lack of housing, food, childcare)
- Discomfort with disclosure of HIV status
- Inadequate education about disease and medications
- Challenges regarding access to health care
- Medical, psychiatric, psychological, or cognitive limitations of the caregiver or child
- Foster care/consent
- Potential interference with activities of daily living, especially school, meals, etc.
Deciding When to Initiate ARV Therapy
The clinician should discuss the risks and benefits of a treatment regimen with HIV-infected children and their caregivers, allowing them to make an informed decision regarding initiating therapy. If the potential risks outweigh the benefits, the clinician and family may choose to defer treatment.
In most cases, clinicians should initiate treatment soon after HIV infection is identified in an infant, either immediately or as soon as the resistance profile is available.
Clinicians should initiate treatment in children older than 1 year of age with symptomatic disease or advancing immunosuppression.
Indications for Initiating ARV Therapy in HIV-infected Children >1 Year of Age
Clinical Category |
CD4 Percentage |
Plasma HIV RNA Copy Number |
Recommendation |
AIDS (Clinical category C)* OR |
<15% (Immune category 3)* |
Any value |
Initiate ARV therapy |
Mild-moderate symptoms (Clinical category A or B)* OR |
15-25%** (Immune category 2)* OR |
>100,000 copies/mL*** |
Consider initiating ARV therapy |
Asymptomatic (Clinical category N)* AND |
>25% (Immune category 1)* AND |
<100,000 copies/mL*** |
Many experts would defer therapy and closely monitor clinical, immune, and viral parameters for deterioration |
Modified from the Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection developed by The Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children convened by the National Pediatric and Family HIV Resource Center (NPHRC), The Health Resources and Services Administration (HRSA), and The National Institutes of Health (NIH). June 25, 2003.
* See Appendix A in the original guideline document
** Many experts would initiate therapy if CD4 cell percentage is between 15 and 20% and defer therapy with increased monitoring frequency in children with CD4 cell percentage 21 to 25%.
***There is controversy among pediatric HIV experts regarding the plasma HIV RNA threshold warranting consideration of therapy in children in the absence of clinical or immune abnormalities; some experts would consider initiation of therapy in asymptomatic children if plasma HIV RNA levels were between 50,000 to 100,000 copies/mL.
Initiating and Selecting an ARV Regimen
ARV treatment should be initiated and/or changed by a pediatric HIV Specialist who is experienced with the issues that distinguish pediatric patients from adults (see HIV Specialist Policy in the "Availability of Companion Documents" field).
Clinicians should obtain a maternal and infant (or child) ARV treatment history and should assess the resistance profile in the context of the ARV history before choosing a regimen.
The clinician should initiate an ARV regimen of at least three drugs, including two nucleoside reverse transcriptase inhibitors (NRTIs) in combination with a protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI).
Refer to the original guideline documentation for recommended regimens (Table 4) and for formulations and dosages for each drug (Appendix C).
Key Point: Many of the newer US Food and Drug Administration (FDA)-approved ARV drugs have been released on the market without specific pediatric formulations; however, pediatric clinicians should still consider using these drugs as part of their armamentarium after consulting with a pediatric HIV Specialist.
Key Point: In HIV-infected children, especially infants, drug-drug interactions and pharmacokinetic parameters related to age/developmental stage should be considered when selecting components of the treatment regimen. In some children, the doses may exceed those recommended for HIV-infected adults.
Drug-related Considerations when Choosing an ARV Regimen
Ease of Administration:
- Availability and palatability of a pediatric formulation
- Patient's ability to swallow pills/soft gel caps
- Frequency of dosing (once a day [qd], twice a day [bid], three times a day [tid], four times a day [qid])
- Food effects
- Storage requirements (e.g., refrigeration)
Safety and Efficacy:
- Age-related pharmacokinetics
- Efficacy of therapeutic regimen
- Durability of antiretroviral effect
- Drug interactions
- Adverse reactions
- Safety in pregnancy (for female adolescents)
- Likelihood of resistance
Follow-Up Monitoring for Patients Receiving ARV Therapy
Children receiving highly active antiretroviral therapy (HAART) should be followed by a pediatric HIV Specialist either as their primary care clinician or through consultation with their primary care clinician.
Clinicians should either contact patients/caregivers by phone or arrange to see them in person 1 to 2 weeks after initiating therapy to monitor adherence and assess for side effects.
Monitoring for Efficacy
Clinicians should obtain a repeat viral load within 4 to 6 weeks after initiating or changing ARV therapy. If there is no decrease in viral load, adherence should be reviewed.
Clinicians should routinely obtain lymphocyte subsets and viral load every 3 to 4 months. Children with significant ongoing viral replication may require more frequent monitoring.
Clinicians should repeat all tests that suggest a significant change (either positive or negative) in plasma RNA copy numbers.
Key Point: The goal of ARV therapy should be an undetectable plasma viral load, which is defined as <400 copies/mL or <40 to 50 copies/mL (with ultrasensitive assay). If this is not achievable, realistic expectations of available therapy should dictate an acceptable level of viremia for each child.
Monitoring for Toxicities and Side Effects
Clinicians should perform a history, physical examination, and laboratory monitoring for toxicity within 4 weeks after initiating ARV therapy and should repeat these at least every 3 months in children receiving ARV therapy.
Laboratory assessments for toxicity should include CBC, assessment of renal and hepatic function, amylase, lipase, and glucose.
When nevirapine is initiated, the clinician should obtain serum liver enzymes every 2 weeks until 6 weeks after initiating therapy, and then monthly for 3 to 4 months.
Screening of serum cholesterol, triglycerides, low-density lipoprotein, and high-density lipoprotein should be performed in HIV-infected children initiating HAART, 3 to 6 months after initiation and approximately every 6 months thereafter. Abnormal results warrant repeat studies performed in the fasting state.
Clinicians should assess lactic acid levels in patients receiving nucleoside reverse transcriptase inhibitors (NRTIs) who develop clinical manifestations (abdominal pain, anorexia, nausea/vomiting, hyperventilation, and/or myalgias) or laboratory markers suggestive of lactic acidosis.
Key Point: Although some adverse events do not warrant stopping therapy, others, such as a hypersensitivity reaction to abacavir or hepatitis associated with nevirapine, require prompt recognition of symptoms and permanent interruption of the drug. Failure to recognize these symptoms may lead to death.
Monitoring Adherence
The clinician should regularly discuss the importance of consistent adherence to the ARV regimen with the caregiver and the child in an age-appropriate way.
At each visit, clinicians should assess adherence in children and adolescents receiving ARV therapy. In cases in which adherence becomes problematic and cannot be resolved, simplification or discontinuation of therapy should be included as a potential management strategy.
Key Point: Challenges of adherence change as HIV-infected children age and enter different developmental stages.
Changing HAART Regimen
Decisions regarding changing therapy should be individualized and should be made in consultation with a pediatric HIV Specialist.
The clinician should decide whether to change therapy, or modify or continue the present regimen in any of the following circumstances:
- Clinical progression
- Sustained increase in viral load
- Progressive immunodeficiency
- Significant toxicity
- Significant unmodifiable adherence issues have developed with the current regimen
When new regimens are selected because of virologic failure, the clinician should perform resistance testing while the child is still on the failing regimen (see "Genotypic/Phenotypic Resistance Testing" section).
When the regimen is changed because of virologic failure, clinicians should switch all drugs at the same time. Ideally, the new regimen should have three new active drugs that the child has not previously taken and that are not cross-resistant to medications the child has taken.
The clinician should discuss the risks and benefits of the specific medications under consideration with the family and child when changing treatment.
Key Point: When virologic suppression has been achieved but therapy needs to be changed because of toxicity, one drug may be substituted for another provided that the new drug is of equal potency.
Considerations when deciding whether to change therapy:
- Previous ARV therapy and resistance profile
- Likelihood of adherence (see "The Importance of Treatment Adherence" section)
- Clinical and immunologic status
- The child's ability to take and tolerate the medications
- The likelihood of achieving complete viral suppression
- The possibility of toxicities or drug-drug interactions.
PI- and Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI)-Experienced Children: Salvage Therapies
The choice of salvage therapy in PI- and NNRTI-experienced children should be made on a case-by-case basis and should be guided by the child's ARV history, resistance profile, and ability to adhere to a regimen.