Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection

The information in the brief version is excerpted directly from the full-text guidelines. The brief version is a compilation of the tables and boxed recommendations.

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When to Initiate Therapy in Antiretroviral-Naive Children

Last Updated: April 16, 2019; Last Reviewed: April 16, 2019

Panel’s Recommendations on When to Initiate Therapy in Antiretroviral-Naive Children
Panel’s Recommendations
  • Antiretroviral therapy (ART) should be initiated in all antiretroviral-naive infants and children with HIV infection (AI, AI* or AII; see Table A for details).
    • Rapid ART initiation (within 1-2 weeks of diagnosis) including an expeditated discussion of adherence is recommended for all children <12 months and those with CDC Stage 3-defining conditions.
    • In other situations, sufficient time to fully assess and address issues associated with adherence should be allowed prior to ART initiation.
  • Every 3 to 4 months, health care providers should closely monitor the virologic, immunologic, and clinical status of any child with HIV who has not initiated ART (AIII).
Rating of Recommendations: A = Strong; B = Moderate; C = Optional

Rating of Evidence: I = One or more randomized trials in children with clinical outcomes and/or validated endpoints; I* = One or more randomized trials in adults with clinical outcomes and/or validated laboratory endpoints with accompanying data in children from one or more well-designed, nonrandomized trials or observational cohort studies with long-term clinical outcomes; II = One or more well-designed, nonrandomized trials or observational cohort studies in children with long-term outcomes; II* = One or more well-designed, nonrandomized trials or observational studies in adults with long-term clinical outcomes with accompanying data in children† from one or more similar nonrandomized trials or cohort studies with clinical outcome data; III = Expert opinion

Studies that include children or children/adolescents, but not studies limited to post-pubertal adolescents

Table A. Treatment Recommendations for Initiation of Therapy in Antiretroviral-Naive Infants and Children with HIV
Age Criteria Recommendation
<12 Monthsa Regardless of clinical symptoms, immune status, or viral load Rapid initiationb of treatment (AII, but AI for children aged ≥6 weeks to <12 weeks)
1 Year to <6 Years CDC Stage 3-defining conditionsc Rapid initiationb of treatment (AI*)
CDC Stage 3 immunodeficiency:d CD4 cell count <500 cells/mm3
Moderate HIV-related symptomsc Treate (AII)
CD4 cell countc 500–999 cells/mm3
Asymptomatic or mild symptomsc and CD4 cell countc ≥1,000 cells/mm3 Treate,f (AI*)
≥6 Yearsg CDC Stage 3-defining conditionsc Rapid initiationb of treatment (AI*)
CDC Stage 3 immunodeficiency:d CD4 cell count <200 cells/mm3
Moderate HIV-related symptomsc Treate (AII)
CD4 cell countd 200–499 cells/mm3
Asymptomatic or mild symptomsc and CD4 cell count ≥500 cells/mm3 Treate,f,g (AI*)
Rating of Recommendations: A = Strong; B = Moderate; C = Optional

Rating of Evidence: I = One or more randomized trials in children with clinical outcomes and/or validated endpoints; I* = One or more randomized trials in adults with clinical outcomes and/or validated laboratory endpoints with accompanying data in children from one or more well-designed, nonrandomized trials or observational cohort studies with long-term clinical outcomes; II = One or more well-designed, nonrandomized trials or observational cohort studies in children with long-term outcomes; II* = One or more well-designed, nonrandomized trials or observational studies in adults with long-term clinical outcomes with accompanying data in children from one or more similar nonrandomized trials or cohort studies with clinical outcome data; III = Expert opinion

Studies that include children or children and adolescents but not studies limited to post-pubertal adolescents
a Treatment of infants aged ≤2 weeks is complex, and it is an area of active investigation. See Antiretroviral Management of Newborns with Perinatal HIV Exposure or Perinatal HIV.
b Within 1 week–2 weeks, including an expedited discussion on adherence.
c See Table 6 for definitions.
d CD4 cell counts should be confirmed with a second test to meet the treatment criteria before initiating ART.
e Allow sufficient time to fully assess and address issues associated with adherence prior to initiating therapy.
f Patients and caregivers, together with their health care providers, may (on a case-by-case basis) decide to defer therapy due to clinical and/or psychosocial factors. Patients should be monitored closely in these cases.
g For adolescents aged ≥13 years with SMRs of 4 or 5, see the Adult and Adolescent Antiretroviral Guidelines.

Note: Potential barriers to adherence should be assessed and discussed with children who have HIV and their caregivers before initiation of therapy (AIII).

Key to Acronyms: ART = antiretroviral therapy; CD4 = CD4 T lymphocyte; CDC = Centers for Disease Control and Prevention; SMR = sexual maturity rating

Table 5: HIV Infection Stage Based on Age-Specific CD4 Cell Count or Percentage
Stagea Age at the Time of the CD4 Test
<1 Year % 1 to <6 Years % ≥6 Years %
Cells/µL Cells/µL Cells/µL
1 ≥1,500 ≥34 ≥1,000 ≥30 ≥500 ≥26
2 750–1,499 26–33 500–999 22–29 200–499 14–25
3 <750 <26 <500 <22 <200 <14
a The stage is based primarily on the CD4 cell count; the CD4 cell count takes precedence over the CD4 percentage, and the percentage is considered only when the count is missing. If a Stage 3-defining condition has been diagnosed (see Table 6), then the stage is 3 regardless of CD4 test results.

Source: Centers for Disease Control and Prevention. Revised surveillance case definition for HIV infection—United States, 2014. MMWR 2014;63(No. RR-3):1-10.

Key to Acronyms: CD4 = CD4 T lymphocyte

Table 6. HIV-Related Symptoms and Conditions
Mildly Symptomatic
Children with two or more of the conditions listed, but none of the conditions listed in the Moderate Symptoms category:
  • Lymphadenopathy (lymph nodes are ≥0.5 cm at more than two sites and/or bilateral at one site)
  • Hepatomegaly
  • Splenomegaly
  • Dermatitis
  • Parotitis
  • Recurrent or persistent upper respiratory tract infection, sinusitis, or otitis media
Moderately Symptomatic
  • Anemia (hemoglobin <8 g/dL [<80 g/L]), neutropenia (white blood cell count <1,000 per µL [<1.0 × 109 per L]), and/or thrombocytopenia (platelet count <100 × 103 per µL [<100 × 109 per L]) persisting for ≥30 days
  • Bacterial meningitis, pneumonia, or sepsis (single episode)
  • Candidiasis, oropharyngeal (thrush), persisting for >2 months in children aged >6 months
  • Cardiomyopathy
  • Cytomegalovirus infection, with onset before age 1 month
  • Diarrhea, recurrent or chronic
  • Hepatitis
  • HSV stomatitis, recurrent (more than two episodes within 1 year)
  • HSV bronchitis, pneumonitis, or esophagitis with onset before age 1 month
  • Herpes zoster (shingles) involving at least two distinct episodes or more than one dermatome
  • Leiomyosarcoma
  • Lymphoid interstitial pneumonia or pulmonary lymphoid hyperplasia complex
  • Nephropathy
  • Nocardiosis
  • Persistent fever (lasting >1 month)
  • Toxoplasmosis, onset before age 1 month
  • Varicella, disseminated (complicated chickenpox)
AIDS-Defining Conditions
  • Bacterial infections, multiple or recurrenta
  • Candidiasis of bronchi, trachea, or lungs
  • Candidiasis of esophagus
  • Cervical cancer, invasiveb
  • Coccidioidomycosis, disseminated or extrapulmonary
  • Cryptococcosis, extrapulmonary
  • Cryptosporidiosis, chronic intestinal (>1 month duration)
  • CMV disease (other than liver, spleen, or lymph nodes), onset at age >1 month
  • CMV retinitis (with loss of vision)
  • Encephalopathy attributed to HIVc
  • HSV: chronic ulcers (>1 month duration) or bronchitis, pneumonitis, or esophagitis (onset at age >1 month)
  • Histoplasmosis, disseminated or extrapulmonary
  • Isosporiasis, chronic intestinal (>1 month duration)
  • Kaposi sarcoma
  • Lymphoma, Burkitt (or equivalent term)
  • Lymphoma, immunoblastic (or equivalent term)
  • Lymphoma, primary, of brain
  • Mycobacterium avium complex or Mycobacterium kansasii, disseminated or extrapulmonary
  • Mycobacterium tuberculosis of any site, pulmonary, disseminated, or extrapulmonary
  • Mycobacterium, other species or unidentified species, disseminated or extrapulmonary
  • Pneumocystis jirovecii (previously known as Pneumocystis carinii) pneumonia
  • Pneumonia, recurrentb
  • Progressive multifocal leukoencephalopathy
  • Salmonella septicemia, recurrent
  • Toxoplasmosis of brain, onset at age >1 month
  • Wasting syndrome attributed to HIVc
a Only among children aged <6 years.
b Only among adults, adolescents, and children aged ≥6 years.
c Suggested diagnostic criteria for these illnesses, which might be particularly important for HIV encephalopathy and HIV wasting syndrome, are described in the following references:
  • Centers for Disease Control and Prevention. 1994 Revised classification system for human immunodeficiency virus infection in children less than 13 years of age. MMWR. 1994;43(No. RR-12).
  • Centers for Disease Control and Prevention. 1993 Revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR. 1992;41(No. RR-17).
Key to Acronyms: CDC = Centers for Disease Control and Prevention; CMV = cytomegalovirus; HSV = herpes simplex virus

Modified from:
  • Centers for Disease Control and Prevention. 1994 revised classification system for human immunodeficiency virus infection in children less than 13 years of age. MMWR. 1994;43(No. RR-12).
  • Centers for Disease Control and Prevention: Revised Surveillance Case Definition for HIV Infection—United States, 2014. MMWR. 2014;63(No. RR-3):1-10.

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