Pediatric HIV
(full text of 2009 Guidelines: Evaluation and Management of the Infant Exposed to HIV-1 in the United States)

Problem: CD4+ cells are infected (including T helper lymphocytes and macrophages) which affects both the humoral and cellular arms of the immune system

Definition of AIDS: When opportunistic or persistent infections have occurred or when the CD4 count is less than 200 in a child >12 yrs old.

Epidemiology

• 90% of reported AIDS cases in U.S. are due to perinatal acqusition

• One of the fastest growing rates of HIV infection is in adolescents

• 2000 children/day infected with HIV in year 2002 in developing countries

• Children “At Risk” for HIV infection:

  • Infants born to HIV-infected mothers, including breastfeeding

  • Blood transfusion recipients

  • Blood products screened for HIV Ab after 1985

  • Sexual abuse victims􀂄Adolescents with “adult” risk behaviors

Signs and Symptoms

• General
  • Fevers/Malaise
  • Lymphadenopathy-high viral burden and replication
  • Hepatomegaly-replication of HIV w/in RES, fatty infiltration, CMV inclusion bodies
• Growth Delay-can be detected as early as 4-6 months.

  Mechanisms: Low-energy intake, GI malabsorption, increased energy expenditure, psychosocial issues

• Neuro:
  • Developmental delay-viral replication in glial cells and inflammation
  • Encephalopathy
• Dermatitis or other skin manifestations-infectious &/or atopic
• Parotitisor Parotid swelling-CD8 lymphocytic infiltration. Bilateral parotitis? think HIV!!
• Hematologic and Bone Marrow Abnormalities
  • ITP <1 y.o.-think HIV!!!
  • Malignancy-I.e. non-Hodgkin's lymphoma
• Cardiomyopathy
• Nephropathy
• Diarrhea or other GI dysfunction

AIDS-defining infections

• Opportunistic infections
  • Pneumocystis jiroveci pneumonia
  • CMV disease
  • Invasive candidiasis
  • Mycobacterium avium complex
  • Cryptococcal meningitis
• Severe bacterial infections
• Lymphoid interstitial pneumonia
• HIV wasting syndrome
• HIV encephalopathy
• Opportunistic malignancies: Kaposi Sarcoma, Lymphoma

HIV testing

• If <18 months old:
  • HIV ab is NOT a reliable test, as maternal Ab is still present
  • HIV DNA PCR at birth, 1 month, and after 4 months
  • HIV p24 antigen (less sensitive, not recommended)
  • HIV RNA PCR (viral load, negative test cannot r/o HIV infxn)
• If >18 months old:
  • HIV antibody (ELISA)
  • Western Blot (confirmatory)
• CBC-lymphopenia, often shows atypical lymphocytes
• Ig levels may be high (elevated Pr/Alb)
• CD4/CD8 <1
• May have mild anemia, thrombocytopenia, or neutropenia
• May have elevated liver enzymes

Lab Monitoring

• CD4+ "helper" T cell number
  1. Indicates risk for opportunistic infections
  2. Bactrim prophylaxis
  3. Higher is better
• HIV RNA number "viral load"
  1. Predicts disease progression
  2. Decreased level is predictive of treatment effects
  3. Lower is better

Mother to Child Transmission

1. Natural hx of HIV: 25% ransmission rate
2. If use AZT-antepartum,intrapartum, and for the newborn: 5-8%transmission rate
3. If use highly active antiretroviral therapies including AZT-antepartum, intrapartum, and for the newborn: 1-2%transmission rate

Treatment

• Nucleoside reverse transcriptase inhibitors (NRTI's)-controls viral replication; requires intracellular phosphorlyation for activation

  • Zidovudine (AZT)

  • Lamivudne (3 TC)

  • Didanosine (ddI)

• Non-nucleoside reverse transcriptase inhibitors (NNRTI's)-controls viral replication

• Nevirapine (NVP)

• Elfavirenz (EFV)

• Protease inhibitors (PI's)-interferes with viral maturation

• Nelfinavir (NFV)

Pneumocystis jiroveci Prophylaxis. Use Bactrim or dapsone.

• Birth to 1 mos (HIV exposed) - No prophylaxis
• 1 to 4 month (HIV exposed) - Prophylaxis
• 4-12 month
  • HIV infected or indeterminate…………Prophylaxis
  • HIV infection excluded………………...No prophylaxis
• 1-5 year and HIV infected
  1. Prophylaxis if: CD4+ T-cell count <500 cells/uL or <15%
• 5 years or greater and  HIV infected
  1. prophylaxis if: CD4+ T-cell count <200 cells/uL or <15%

Guidelines for Anti-Retroviral Treatment

1. Use combination of drugs (at least 3) to maximize the antiviral effect and minimize cross-resistance
2. Monitor HIV RNA and CD4 T-cell counts
3. Reduce HIV RNA as much as possible for as long as possible
4. Immunizations:
   1. Standard immunizations are recommended for children who have HIV infection
   2. Annual influenza recommended
   3. Varicella vaccine has been shown to be safe and immunogenic in HIV-infected children who have normal CD 4 counts
   4. Live viral vaccines should never be administered to children who have the lowest CD 4 counts.

CHLA Board Review 2005