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PEDIATRIC HIV UPDATE NAZHA ABUGHALI, MD 5/31/02

PEDIATRIC HIV UPDATE NAZHA ABUGHALI, MD 5/31/02. Dr. Nazha Abughali is Assistant Professor of Pediatrics Case Western Reserve University Head of Pediatrics TB Services, MetroHealth Medical Center. Global Epidemiology Of HIV.

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PEDIATRIC HIV UPDATE NAZHA ABUGHALI, MD 5/31/02

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  1. PEDIATRIC HIV UPDATE NAZHA ABUGHALI, MD 5/31/02 Dr. Nazha Abughali is Assistant Professor of Pediatrics Case Western Reserve University Head of Pediatrics TB Services, MetroHealth Medical Center

  2. Global Epidemiology Of HIV • 34.3 million individuals living with HIV/AIDS world wide. • 24.5 million are living in sub-Saharan Africa. • 620,000 of children were estimated to be newly infected in 1999. • 1.3 million children estimated to be living with HIV/AIDS. • 3.8 million death in children due to HIV/AIDS and 13.2 million AIDS orphans since the beginning of the epidemics. * Report on the global HIV/AIDS epidemic, 6/ 2000.

  3. Timing of maternal -infant transmission • Intrauterine: 25-40% • Intrapartum: 60-75%. • Added risk of breast -feeding : 12-14%.

  4. Maternal- Infant Transmission • In the absence of antiretroviral use transmission rates 16-40%. • AZT prophylaxis and the use of HAART in pregnant women had resulted in a persistent drop in rates of perinatal HIV transmission to rates of 5-6% and even 2% in those with undetectable viral loads.

  5. Pediatric AIDS Clinical Trial Group (PACTG) 076 • In placebo -controlled clinical trial the use of AZT in pregnant women starting at 14-34 weeks till delivery, intravenous AZT during labor and oral AZT to the infants from birth till 6 weeks of age resulted in a 67.5% reduction in HIV transmission: 25.5% in the placebo compared to 8.5% in the AZT group.

  6. In August 1994, the US Public Health Services recommended the use of AZT to reduced the risk of perinatal HIV transmission. • In 1995 the USPHS and the AAP recommended routine HIV counseling and voluntary testing to all pregnant women. • Since then there had been persistent decrease in the rate of perinatal transmission.

  7. PREVENTION OF PEDIATRIC HIV • Early identification of HIV infected women before pregnancy, during pregnancy or during labor is crucial for : - prevention of HIV vertical transmission to the neonates. - Counseling against breast-feeding in the U.S. - Early identification of infected newborns, and thus, early initiation of HAART and PCP prophylaxis. - Early initiation of appropriate medical care for the mother.

  8. Guidelines for prevention of perinatal HIV transmission • Early maternal HIV diagnosis and initiation of appropriate antiretoviral therapy before or during pregnancy. Try to incorporate AZT. • Use of standard AZT prophylaxis regimen: intrapartum and neonatal AZT for 6 weeks. • C-section: recommended for mothers with HIV viral load > 1000 copies/ml (obtained at 36 weeks).* * exceptions: PROM and /or labor> 4 hours.

  9. Recommendation for for HIV-infected mother in labor who had no prior therapy 1. Single dose Nevirapine during labor and a single dose to the neonate at age 48h. 2.Oral AZT and 3TC during labor, and one week of this combination to the neonate. 3. Intrapartum AZT, the 6 weeks of AZT to the neonate. 4. The two dose Nevirapine combined with the intrapartum and 6 weeks AZT regimen.

  10. IN case of maternal HIV antiretroviral resistance: AZT is still recommended to the infant, plus other medications based on maternal HIV resistance pattern.

  11. Diagnosis of HIV Child aged < 18 months: • HIV can be diagnosed : two positive virological assays* obtained from two different blood samples, excluding cord blood. • HIV can be excluded: 1) 2 negative HIV virological tests, 1 performed age >1 month and the other age > 4 months. 2) 2 negative HIV antibody tests performed after age 6 months, obtained one month apart. • * HIV viral culture, HIV PCR DNA/RNA

  12. Child aged > 18 months, or adolescents/adults: • HIV can be diagnosed by: 1)A repeatedly positive HIV antibody test , followed by a confirmatory test (western blot). • 2) A positive HIV virological test result: HIV PCR RNA/DNA, viral culture… • HIV can be excluded: 0ne negative HIV antibody, in the absence of hypoglobulinemia with negative virological tests and no clinical symptoms of HIV.

  13. HIV pediatric classification: clinical Categories • Category N: Not symptomatic or have one clinical entity of category A. • Category A: 2 of the following with none of B or C: Lymphadenopathy (more thane one site), hepatomegaly, Splenomegaly, dermatitis, parotitis, recurrent or persistent URI, sinusitis or otitis media.

  14. Category B: Moderately symptomatic Anemia( <8mg/dl), neutropenia (<1000/ml) or thrombocytopenia (<100,000/ml) persisting >30 days. Bacterial meningitis, pneumonia, sepsis. Candidiasis>2 months in older than 6 months old children. CMV infection with onset before 1 month of age. Chronic or recurrent diarrhea Recurrent HSV stomatitis, HSV bronchitis, or esophagitis in age <1 month. Herpes zoster involving more than one dermatome or at least 2 episodes. Or disseminated varicella Toxoplasmosis starting <one month of age. Others: cardiomyopathy, leiomyosarcoma, Nocardiosis, nephropathy, and fever> 1 month.

  15. Category C : Severely symptomatic( AIDS serious bacterial infections: multiple or recurrent (culture positive events, pneumonia, meningitis, septicemia). Candida: esophageal or pulmonary. Disseminated coccidioidmycosis, disseminated Histoplasmosis Cryptococosis, crypotosporidiosis, isopspriosis with diarrhea >1 month. CMV disease in children>1 months of age. Encephalopathy, PML, Wasting syndrome. HSV: pneumonitis, esophagitis children >1 months old. PCP, MTB disseminated or extrapulmonary, Salmonella septicemia, Toxoplasmosis. Disseminated non-tuberculous mycobacteria. Malignancies: Kaposis sarcoma, lymphomas.

  16. Immunological Classification of Pediatric HIV Age specific CD4+ T-lymphocyte count and % of total Class <12mo 1-5Y 6-12Y 1 1500 25% 1000 25% 500 25% 2 750-1499 15-24% 500-999 15-24% 200-499 15-24% 3 <750 <15% <500 <15% <200 <15%

  17. Care of the HIV- Exposed Neonate • After Birth: • AZT : 2mg/kg Q 6 hr for 6 weeks. If mother has HIV resistant to AZT then might give additional meds. • HIV PCR DNA with-in 48 hour of birth. • Base-line CBC. • Hepatitis B vaccine. • 2 weeks : • HCT. Check for compliance with meds. • Optional HIV DNA PCR.

  18. 2 Months: Well child visit. HIV PCR, CBC. AZT stopped at 6 weeks. Start Bactrim prophylaxis. Give the usual immunizations. 4 Months: Well child visit. HIV PCR. Immunizations. 6 Months: Well child visit. Immunizations Stop Bactrim if all HIV PCR’s are negative.

  19. 12 Months: well child visit. Immunizations. 15 Months: Well Child visit . Immunizations. 18 Months: Well child visit. Immunizations. HIV antibody. If negative and child asymptomatic the patient is discharged of the HIV clinic.

  20. All HIV exposed children who were exposed to antiretroviral therapy in utero, should be followed up till adulthood for any potential future carcinogenicity . If any of those children develop significant organ system abnormalities of unknown etiology, particularly involving the CNS and the heart. They should be evaluated for potential mitochondrial dysfunction. Pap smears should be performed on adolescent girls.

  21. Care of the HIV infected child: Start HAART as soon as possible. Obtain CBC, CD4+ T-cell count, HIV viral load Q2-3 months. Blood for chemistries, LFT’s, amylase lipase, lipid profile are obtained Q3-6 months. Immunoglobulins yearly. PPD yearly CXR and urine analysis yearly. Clinic visit: Q2-3 months. Emphasis on growth and development, social issues and compliance.

  22. Care of the infected child Immunization:Give same vaccine as non-infected, except for : • Prevnar is recommendedeven in older children plus the pneumoccocal polysaccharide vaccine. • Flu vaccine is recommended for > 6 months of age. • Varicella vaccine consider only for ClassA1N1. • MMR is contraindicated for immunological class 3.

  23. Antiretroviral Therapy • 1993 AZT monotherapy was recommended as the standard of care for the treatment of symptomatic HIV infected children. • 1998 recommended the use of HAART and the monitoring of HIV RNA viral load and CD4+ T-cell counts as tools to assess treatment progress.

  24. Antiretroviral Therapy in childrenRational and considerations • The majority of children acquire their HIV infection close to the time of birth and therefore, are considered to have primary HIV infection. Thus, the importance of initiation of HAART early on. • The immune system of the neonates is in the developing period, thus their virological and immunological markers are different than the adults.

  25. Considerations for Antiretroviral therapy in children • Treatment in neonates occur in the context of previous antiretroviral therapy in utero and intrapartum. • Drug pharmacokinetics changes in the transition from infancy to adulthood. • Special social issues in general and compliance issues in particular are important in the management of pediatric HIV.

  26. Monitoring of treatment progress • Immunological parameters: absolute CD4+ T-cells and their %. • HIV viral load. • Clinical parameters: growth and development and the occurrence of infectious complications. • Check for drug toxicity.

  27. Indications for initiation of HAART • Clinical symptoms: class A, B or C. • Immunological indications: category 2 or 3. • Age 12 months initiate therapy regardless of clinical, immunological or virological indications.

  28. Indications for initiation of HAART • Asymptomatic children Age >12 months with normal immune status: 1) Initiate therapy regardless of age or symptoms 2) Defer treatment in situations where the risk of progression is low and other factors favor postponing treatment. Follow closely and start if: -A. High or increasing viral load. B. Rapidly declining CD4 count or %. C. Development of clinical symptoms.

  29. HIV RNA PCR Assay Caveats • Biological variations in the same individual ( up to three fold. • Viral load in perinatally infected children can be very high in the first year of life, then gradually decrease spontaneously, without therapy : average of 0.6 log/year in the first 2 years of life. Slower decline continues till age 4-5 years (average 0.3 log/year). • Concurrent infection or even immunizations can cause an increase in the viral load.

  30. HIV viral RNA load as an indication for initiation of therapy • Regardless of age viral RNA >100,000 copies/ml is associated with high risk of mortality. • In children aged >30 months the risk of death is very low at viral load <15,000 copies/ml, above that level risk increases to >13%.

  31. HIV viral RNA load as an indication for initiation of therapy • Children age <2 years with >0.7 log or 5 fold increase should be offered HAART. • Children ages >2 years with >0.5 log or 3 fold increase should be offered HAART.

  32. Choice of Antiretroviral therapy • The goal of the medications is to: 1)maximally suppress viral replications, 2)preserve/restore immune function and 3)minimize toxicity. • Before starting therapy: It is important to discuss with the caregiver the importance of compliance with the medications.

  33. ANTIRETROVIRAL MEDICATIONS • Nucleoside reverse transcripatseinhibitors: AZT, DDI, DDC, 3TC, D4T, Abacavir. Tenofovir and Adefovir. Toxicity: Mitochondrial dysfunction due to the inhibition of mitochondrial DNA polymerase gamma. Toxicity include: lactic acidosis, hepatic steatosis, pancreatitis, myopathy and peripheral neuropathy. Some toxicities are specific to individual meds: ex: hematological with AZT, fatal hypersensitivity reaction due to Abacavir.

  34. Non-nucleoside reverse transcriptase inhibitors: ex: Nevirapine, Delaviradine, Efavirenz.. Resistance can occur very rapidly and can confer resistance to the whole class. Toxicity: rashes, hepatotoxicity. Protease Inhibitors: Ritonavir, Nelfinavir, Indinavir, Saquinavir, Saquinavir soft Gel Cap, Amprenavir, Lopinavir/ritonavir( Kaletra). Toxicity: lipodystrophy with fat redistribution and hyperlipidemia. Hyperglycemia. Kidney stones with Indinavir

  35. Recommended Antiretroviral Regimens for initial Treatment • Strongly recommended: • PI (nelfinavir or Ritonavir) and 2 NRTI *. • NNRTI ( sustiva) plus 2 NRTI, or one NRTI and PI ( nelfinavir). * NRTI combinations: AZT/ddI, AZT/3TC, d4T/ddI, d4T/3TC.

  36. Recommended as Alternative therapy • Nevirapine (NNRTI) and 2 NRTI’s. • Abacavir (NRTI) and AZT, 3TC. • Kaletra ( Lopinavir/ritonavir)and 2 NRTIs, or one NRTI and one NNRTI. • Indinavir or Saquinavir soft gel capsules and 2 NRTI.

  37. Offered in special circumstances: Two NRTIs. Amprenavir with either 2 NRTIs or Abacavir. Not recommended: Any monotherpay. d4T/AZT ddC with either ddI or d4T or 3TC.

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