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Pediatric HIV: Comprehensive Management Notes

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1. ETIOLOGY & VIROLOGY

• HIV-1 and HIV-2 are cytopathic lentiviruses (family Retroviridae, genus Lentivirus)
• HIV-1 is the predominant global strain; has 3 genetic groups (M, O, N) and 8 clades (A-K)
• HIV-2: predominant in West Africa; milder course; intrinsically resistant to NNRTIs and enfuvirtide - this changes treatment selection
• Virus persists in latent reservoirs: peripheral blood mononuclear cells, brain, bone marrow, genital tract - even when plasma viral load is undetectable
• Infectious body fluids: blood, semen, cervicovaginal secretions, breast milk

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2. TRANSMISSION IN CHILDREN

Routes

MTCT Risk Factors

• Maternal viral load = most critical determinant (transmission documented across all viral load ranges)
• Without treatment: ~25% MTCT risk (US, no breastfeeding)
• Without treatment + breastfeeding to 12 months: ~25% + additional postnatal risk
• With maternal ART achieving viral suppression: risk reduced to <1-2%

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3. CLINICAL PRESENTATION

Acute/Early Presentation in Infants

• Most perinatally infected infants are asymptomatic at birth
• Without ART, HIV in infants progresses faster than adults; ~20% develop AIDS or die within the first year
• Signs: failure to thrive, persistent oral candidiasis, recurrent bacterial infections, generalized lymphadenopathy, hepatosplenomegaly, parotid enlargement, developmental delay/encephalopathy

Common Opportunistic Infections (Pre-ART Era / Untreated)

• Pneumocystis jirovecii pneumonia (PCP) - most common serious OI, especially 2-6 months of age
• Candida (esophageal)
• CMV (retinitis, pneumonitis, colitis)
• Mycobacterium avium complex (MAC)
• Cryptococcus neoformans (meningitis)
• Herpes simplex, VZV (severe disseminated)
• Toxoplasma gondii
• Cryptosporidium species

HIV-Associated Malignancies in Children

• Non-Hodgkin B-cell lymphoma (Burkitt type, including CNS)
• Leiomyosarcomas
• Kaposi sarcoma (rare in US; more common in HIV-infected children from sub-Saharan Africa)
• Incidence of all malignancies decreased significantly in the ART era

Immune Reconstitution Inflammatory Syndrome (IRIS)

• Paradoxical clinical deterioration shortly after ART initiation in severely immunosuppressed patients
• Caused by inflammatory response as CD4 immunity is restored
• Associated pathogens: Mycobacterium tuberculosis, BCG, herpesviruses, Cryptococcus species
• Management: continue ART; NSAIDs or corticosteroids for severe cases

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4. DIAGNOSIS

In Children < 18 Months

• Maternal IgG antibodies cross the placenta - antibody tests are unreliable (false positive due to passive maternal antibody)
• Use Nucleic Acid Amplification Tests (NAATs):
  • HIV-1 DNA PCR (peripheral blood mononuclear cells) or HIV-1 RNA PCR (plasma)
  • Both are equally recommended; detect 1-10 DNA copies
  • HIV RNA assay detects 25-58% of infected infants in week 1, 60% by 1 month, 90-100% by 2-3 months
  • HIV p24 antigen: NOT recommended (less sensitive, false positives in first month)

Recommended Virologic Testing Schedule for HIV-Exposed Infants:

• Definitive diagnosis of infection: 2 separate positive virologic tests on 2 different blood samples
• Definitive exclusion of infection: 2 negative virologic tests, one at ≥1 month and one at ≥4 months of age (in non-breastfed infants)

Confirming Infection: Algorithm

1. Initial: 4th generation HIV-1/HIV-2 Ag/Ab combination immunoassay
2. If reactive: HIV-1/HIV-2 antibody differentiation immunoassay
3. If reactive on Ag/Ab but nonreactive/indeterminate on differentiation: HIV-1 NAAT

In Children ≥ 18-24 Months

• Standard HIV antibody assays can be used
• Note: 14% of infants remain antibody-positive past 18 months; 4.3% past 21 months; 1.2% past 24 months

Monitoring Tests (Once Diagnosed)

• CD4+ T-lymphocyte count and percent - immunologic staging
• Plasma HIV RNA (viral load) - disease progression predictor and treatment monitoring
• Resistance testing before or at ART initiation

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5. CDC IMMUNOLOGIC CLASSIFICATION (Age-Based CD4 Thresholds)

Key: CD4 percentage is more stable than absolute count in young children and is preferred for immunologic staging under age 5.

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6. ANTIRETROVIRAL THERAPY (ART)

When to Start ART

• All HIV-infected children and adolescents should receive ART, regardless of clinical status, CD4 count, or viral load
• ART should be initiated as soon as possible after diagnosis
• Treatment should never be delayed for resistance testing - start empirically, adjust when results return
• Expert consultation (pediatric HIV specialist) is strongly recommended

Goals of ART

1. Achieve and maintain undetectable viral load (viral suppression)
2. Preserve/restore immune function (CD4 recovery)
3. Prevent opportunistic infections
4. Enable normal growth and development
5. Reduce MTCT if applicable (adolescent females)

ART Drug Classes

Preferred ART Regimens (Pediatric)

Dolutegravir (DTG) has become the preferred INSTI in most regimens due to: high barrier to resistance, once-daily dosing, minimal drug interactions, good tolerability.

Special Notes on Drug Selection

• Lopinavir/ritonavir (LPV/r): Has considerable sustained activity even in patients who have failed previous PI regimens; liquid formulation available for young infants
• Zidovudine (ZDV/AZT): FDA-approved for children; used both for treatment and MTCT prevention (IV formulation during labor)
• Nevirapine: Used in infants for MTCT prophylaxis; resistance can emerge rapidly if used as monotherapy
• Abacavir: Requires HLA-B*5701 testing before use (hypersensitivity reaction risk)
• Efavirenz: Not recommended under age 3 or <10 kg; CNS side effects

ART Monitoring

Virologic Failure Definition

• Viral load > 200 copies/mL on 2 consecutive measurements after ≥6 months of ART
• Most common cause: poor adherence
• Management: assess adherence first, then resistance testing, then consider regimen switch

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7. PREVENTION OF MOTHER-TO-CHILD TRANSMISSION (PMTCT)

The "4 Prongs" Framework

1. Primary prevention of HIV in women of childbearing age
2. Preventing unintended pregnancies in WLHIV
3. Preventing vertical transmission (maternal ART, obstetric interventions, infant prophylaxis)
4. Care and treatment of mother, infant, and family

Key Interventions

Maternal viral load is the critical determinant: with undetectable VL on ART, MTCT risk is <1-2%. Transmission can still occur (though rarely) at any viral load level.

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8. IMMUNIZATIONS IN HIV-INFECTED CHILDREN

General Principles

• Response to vaccines may be suboptimal in immunocompromised children
• Re-immunization after ART initiation (immune reconstitution) may be needed
• Live vaccines: generally contraindicated in severe immunosuppression (CD4 <15% or <200/mm³)

Key Vaccine Guidance

Post-Exposure Passive Immunization

• Measles exposure: IGIM 0.5 mL/kg (max 15 mL) if asymptomatic with mild-moderate immunosuppression; IGIV 400 mg/kg if severely immunosuppressed (CD4 <15%)
• Varicella exposure: VZIG ideally within 96 hours (up to 10 days); alternative: IGIV 400 mg/kg
• Tetanus: Give TIG for tetanus-prone wounds regardless of immunization status in severely immunosuppressed

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9. OPPORTUNISTIC INFECTION (OI) PROPHYLAXIS

PCP Prophylaxis (Pneumocystis jirovecii)

• Drug of choice: TMP-SMX (cotrimoxazole)
• Indications:
  • All HIV-exposed infants starting at 4-6 weeks until HIV infection is excluded
  • All HIV-infected infants < 12 months (regardless of CD4)
  • Children 1-5 years: CD4 <500 cells/mm³ or <15%
  • Children ≥ 6 years: CD4 <200 cells/mm³ or <15%
• Can discontinue once CD4 rises above threshold on ART for ≥3-6 months

MAC Prophylaxis (Mycobacterium avium complex)

• Azithromycin (preferred) or clarithromycin
• Indicated when CD4 < 50 cells/mm³ (age >6 yrs) or age-appropriate thresholds
• Can discontinue when CD4 improves on ART

Toxoplasma Prophylaxis

• TMP-SMX also covers Toxoplasma gondii
• Indicated if CD4 <100 and IgG positive

Cryptococcal Meningitis Secondary Prophylaxis

• Fluconazole after treatment of acute episode; discontinue when CD4 >100-200 on ART

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10. NUTRITION AND GROWTH MONITORING

• HIV-infected children have higher rates of malnutrition and growth failure
• Regular monitoring: weight, height, head circumference (infants), BMI
• Caloric supplementation often needed, especially during OI episodes
• HIV encephalopathy can impair feeding and development
• Oral candidiasis can cause odynophagia and food aversion - treat promptly with fluconazole or nystatin

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11. NEURODEVELOPMENTAL CONSIDERATIONS

• HIV encephalopathy - can present as developmental delay, cognitive regression, motor difficulties, microcephaly
• Causes: direct viral infection of CNS, OI-related CNS disease, ART toxicity
• Regular developmental assessments at each visit
• Early ART initiation is the best prevention
• Neuroimaging (MRI brain) if neurological signs present

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12. ADOLESCENT-SPECIFIC MANAGEMENT

• Perinatally infected adolescents may have ART resistance from years of treatment
• Adherence issues peak in adolescence - critical to address
• Sexual risk counseling and prevention (HIV transmission to partners)
• Contraception and pre-conception counseling in females
• U=U principle ("Undetectable = Untransmittable") - educate and empower
• Screen for STIs, mental health conditions, substance use
• Transition planning to adult care starting at age 14-16 years

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13. QUICK REFERENCE: RED FLAGS REQUIRING URGENT ASSESSMENT

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14. KEY FORMULAS & TARGETS AT A GLANCE

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15. IRIS MANAGEMENT SUMMARY

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• Red Book 2021: Report of the Committee on Infectious Diseases (AAP), pp. 692-706
• Harriet Lane Handbook, 23rd Edition (Johns Hopkins Hospital)
• NIH Pediatric ARV Guidelines: clinicalinfo.hiv.gov/en/guidelines/pediatric-arv
• Recent evidence: TB incidence post-ART in HIV+ children (PMID 38968268, 2024 Meta-analysis); Mortality rates on ART in HIV+ children (PMID 39085806, 2024 Meta-analysis); Maternal viral load and MTCT risk (PMID 40652949, Lancet 2025)