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Oi pediatrics

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Oi pediatrics

  1. 1. Treating Opportunistic Infection Among HIV-Infected Children
  2. 2. Contents <ul><li>Introduction (slide 3) </li></ul><ul><li>Bacterial, parasitic, and other infections (slide 8) </li></ul><ul><ul><li>Serious and recurrent bacterial infections, syphilis, toxoplasmosis, crypto/microsporidiosis </li></ul></ul><ul><li>Mycobacterial infections (slide 39) </li></ul><ul><ul><li>MTB, MAC </li></ul></ul><ul><li>Fungal infections (slide 61) </li></ul><ul><ul><li>Pneumocystis jiroveci pneumonia, Candida , cryptococcosis, histoplasmosis, coccidioidomycosis </li></ul></ul><ul><li>Viral infections (slide 104) </li></ul><ul><ul><li>CMV, HSV, HZV, HPV, HCV, HBV </li></ul></ul>
  3. 3. Introduction <ul><li>Mother-to-child transmission of OI is an important mode of acquisition </li></ul><ul><li>HIV-infected women coinfected with OI more likely to transmit (e.g., CMV, HCV) </li></ul><ul><li>HIV-infected women or HIV-infected family members are sources of horizontal transmission (eg, tuberculosis) </li></ul>
  4. 4. <ul><li>OI in children often reflects primary infection rather than reactivation </li></ul><ul><li>OI occurs at a time when infant’s immune system is immature </li></ul><ul><li>Different disease manifestations (eg, children more likely to have nonpulmonic and disseminated tuberculosis) </li></ul>Differences between Adults and Children
  5. 5. Difficulty of Diagnosing OI in Children <ul><li>Inability to describe symptoms </li></ul><ul><li>Antibody-based tests confounded by maternal transfer of antibody </li></ul><ul><li>Sputum difficult to obtain without invasive procedures </li></ul>
  6. 6. Frequency of OI among HIV-Infected Children <ul><li>Pre-HAART era, most common OIs occurring at >1 events/100 child years </li></ul><ul><ul><li>Serious bacterial infections (bacteremia and pneumonia), herpes zoster, Pneumocystis jiroveci ( carinii ) pneumonia, candidiasis, Mycobacterium avium complex </li></ul></ul><ul><li>Pre-HAART era, most common OIs occurring at <1 events/100 child years </li></ul><ul><ul><li>Cytomegalovirus, toxoplasmosis, cryptosporidiosis, tuberculosis, systemic fungal infections </li></ul></ul>
  7. 7. Treating OI among HIV-Infected Children <ul><li>Letter indicating strength of recommendation (e.g., A, B, C) </li></ul><ul><li>Roman numeral indicating nature of evidence (e.g., I, II, III) </li></ul>Rating of treatment recommendations is based on opinion of working group
  8. 8. Serious Recurrent Bacterial Infections Epidemiology <ul><li>Most common infection in pre-HAART era (15/100 child years) </li></ul><ul><li>Because of difficulties in obtaining appropriate diagnostic specimens, bacterial pneumonia is often a presumptive diagnosis in a child with fever, pulmonary symptoms, and an abnormal chest radiogram </li></ul><ul><li>Bacteremia more common in HIV-infected children with pneumonia </li></ul>
  9. 9. Serious Recurrent Bacterial Infections Epidemiology <ul><li>Isolated bacteria include Streptococcus pneumoniae , Haemophilus influenzae type B, Staphylococcus aureus , Escherichia coli , Pseudomonas aeruginosa , nontyphoid Salmonella </li></ul><ul><li>Incidence of S pneumoniae and H influenzae may be lower in regions where vaccines are administered </li></ul>
  10. 10. Serious Recurrent Bacterial Infections Clinical Manifestations <ul><li>Clinical presentation dependent on type of bacterial infection, e.g., bacteremia, sepsis, vasculitis, septic arthritis, pneumonia, meningitis, sinusitis </li></ul><ul><li>Presentation similar to that of HIV-uninfected children </li></ul>
  11. 11. Serious Recurrent Bacterial Infections Diagnosis <ul><li>Isolation of pathogenic organism from normally sterile sites – blood, bone marrow, CSF </li></ul><ul><li>Diagnosis of pneumonia by radiograph and physical findings </li></ul><ul><li>Culture of catheter tips </li></ul>
  12. 12. Serious Recurrent Bacterial Infections Treatment <ul><li>Consider local prevalence of resistance of common infectious agents </li></ul><ul><li>Response of mildly immunodeficient children is similar to that of HIV-uninfected children </li></ul><ul><li>Treat HIV-infected children outside the neonatal period with empiric therapy until cultures are available (A III) </li></ul><ul><ul><li>Ceftriaxone: 80-100 mg/kg in 1 or 2 divided doses, or </li></ul></ul><ul><ul><li>Cefotaxime: 150-200 mg/kg divided into 3 or 4 doses, or </li></ul></ul><ul><ul><li>Cefuroxime: 100-150 mg/kg divided into 3 doses </li></ul></ul>
  13. 13. Serious Recurrent Bacterial Infections Treatment <ul><li>Children <5 years should be given H influenza B and heptavalent pneumococcal conjugate vaccines (A II) </li></ul><ul><li>Children >2 years should receive 23 valent pneumococcal vaccine (>2 months after conjugate vaccine) </li></ul><ul><li>Reimmunize with pneumococcal vaccine in 3-5 years in children <10 years or after 5 years in children >10 years </li></ul>
  14. 14. Syphilis Epidemiology <ul><li>Perinatal transmission of Treponema pallidum at any stage of pregnancy or during delivery </li></ul><ul><li>Drug use during pregnancy increases risk of maternal and congenital syphilis </li></ul><ul><li>Rate of congenital syphilis 50 times greater among infants born to HIV-infected mothers </li></ul><ul><li>Half of new infections are in women 15-24 years of age </li></ul>
  15. 15. Syphilis Clinical Manifestations <ul><li>Untreated early syphilis in pregnancy leads to spontaneous abortion, stillbirth, hydrops, preterm delivery, death in up to 40% of pregnancies </li></ul><ul><li>47% of infants born to mothers with inadequately treated syphilis have clinical, radiographic, or laboratory findings consistent with congenital syphilis </li></ul>
  16. 16. Syphilis Clinical Manifestations <ul><li>60% of infants with congenital syphilis have hepatomegaly, jaundice, skin rash, nasal discharge, anemia, thrombocytopenia, osteochondritis, or pseudoparalysis </li></ul><ul><li>Late manifestations include mental retardation, keratitis, deafness, frontal bossing, Hutchinson teeth, saddle nose, Clutton joints </li></ul>
  17. 17. Syphilis Diagnosis <ul><li>Use combination of physical, radiologic, serologic, and direct microscopic results, as standard serologic tests detect only IgG </li></ul><ul><li>All infants born to mothers with reactive nontreponemal and treponemal test should be evaluated with a quantitative nontreponemal test, e.g., slide test, rapid plasma reagin (RPR) </li></ul>
  18. 18. Syphilis Diagnosis <ul><li>Darkfield microscopy or direct fluorescent antibody staining </li></ul><ul><li>Presumptive diagnosis – any infant, regardless of physical findings, born to an untreated or inadequately treated mother with syphilis </li></ul>
  19. 19. Syphilis Treatment <ul><li>Treat all infants whose mothers have untreated or inadequately treated syphilis; treated or initiated treatment 4 weeks prior to delivery </li></ul><ul><li>Treat infants regardless of maternal history if examination suggests syphilis; darkfield or fluorescent antibody test positive or nontreponemal serologic titer = 4-fold higher than maternal (A II) </li></ul>
  20. 20. Syphilis Treatment <ul><li>Aqueous crystalline penicillin G: 100,000-150,000 units/kg/day given as 50,000 units/kg/dose intravenously every 12 hours for 7 days followed by every 8 hours for a total of 10 days (A II) </li></ul><ul><li>Diagnosis after 1 month of age, increase dosage to 200,000-300,000 units/kg intravenously every 6 hours daily for 10 days </li></ul>
  21. 21. Syphilis Treatment <ul><li>Treat acquired syphilis with single dose of benzathine penicillin G 50,000 units/kg IM </li></ul><ul><li>Treat late latent disease with 3 doses of benzathine penicillin G 50,000 units/kg IM once weekly for 3 doses (A III) </li></ul><ul><li>Alternative therapies among HIV-infected patients have not been evaluated </li></ul><ul><li>Follow up with examinations at 1, 2, 3, 6, and 12 months and serologic tests at 3, 6, and 12 months; if titers continue to be positive or increase, consider retreatment (A III) </li></ul>
  22. 22. Toxoplasmosis Epidemiology <ul><li>Primarily perinatal transmission from primary infection of mothers during pregnancy </li></ul><ul><li>Older children acquire toxoplasmosis from poorly cooked food and from ingestion of sporulated oocysts in soil, water, or food </li></ul>
  23. 23. Toxoplasmosis Epidemiology <ul><li>Risk of transmission in HIV-uninfected mothers with primary infection during pregnancy = 29% (lower if maternal infection in first trimester) </li></ul><ul><li>Perinatal toxoplasmosis infection may occur in HIV-positive women with chronic infection </li></ul><ul><li><1% of AIDS-defining illnesses in children </li></ul>
  24. 24. Toxoplasmosis Clinical Manifestations <ul><li>Non-immunocompromised infants are usually asymptomatic at birth but majority develop late manifestations – retinitis, neurologic impairment </li></ul><ul><li>Newborn symptoms can include: </li></ul><ul><ul><li>Rash, lymphadenopathy, jaundice, hematologic abnormalities, seizures, microcephaly, chorioretinitis, hydrocephalus </li></ul></ul>
  25. 25. Toxoplasmosis Clinical Manifestations <ul><li>Toxoplasmosis acquired after birth is initially asymptomatic, followed by infectious mononucleosis-like syndrome </li></ul><ul><li>Chronic toxoplasmosis can reactivate in HIV-infected children </li></ul>
  26. 26. Toxoplasmosis Diagnosis <ul><li>Test all HIV-infected pregnant women for toxoplasmosis </li></ul><ul><li>If positive, evaluate infant for congenital toxoplasmosis </li></ul><ul><li>Use antibody assay to detect IgM-, IgA-, or IgE-specific antibody in first 6 moths or persistence of IgG antibody after 12 months </li></ul>
  27. 27. Toxoplasmosis Diagnosis <ul><li>Additional methods include isolation of toxoplasmosis from body fluids or blood </li></ul><ul><li>Negative antibody does not exclude toxoplasmosis – may require CT, MRI, or brain biopsy in case of encephalitis </li></ul>
  28. 28. Toxoplasmosis Treatment <ul><li>If HIV-positive mother has symptomatic toxoplasmosis during pregnancy, infant should be treated (B III) </li></ul><ul><li>Preferred treatment – congenital toxoplasmosis: </li></ul><ul><ul><li>Pyrimethamine loading dose of 2 mg/kg orally once daily for 2 days; then 1 mg/kg orally once daily for 2-6 months; then 1 mg/kg orally 3 times/week with sulfadiazine 50 gm/kg/dose twice daily and with leucovorin (folinic acid) 10 mg orally with each dose of sulfadiazine (A II) </li></ul></ul><ul><ul><li>Optimal duration of treatment: 12 months </li></ul></ul>
  29. 29. Toxoplasmosis Treatment <ul><li>Pyrimethamine: 2 mg/kg/day (maximum 50 mg/kg) orally for 3 days; then 1 mg/kg/day orally and leucovorin 10-25 mg/day plus sulfadiazine 25-50 mg/kg/dose orally given 4 times daily </li></ul><ul><li>Continue acute therapy for 6 weeks </li></ul><ul><li>Lifelong prophylaxis required </li></ul>Treatment of HIV-infected children with acquired CNS, ocular, or systemic toxoplasmosis
  30. 30. Toxoplasmosis Treatment <ul><li>Pyrimethamine: rash, Stevens-Johnson syndrome, nausea, reversible bone marrow toxicity </li></ul><ul><li>Sulfadiazine: rash, fever, leukopenia, hepatitis, nausea, vomiting, diarrhea, crystalluria </li></ul>
  31. 31. Toxoplasmosis Alternative Treatment <ul><li>Azithromycin: 900-1,200 mg/kg/day with pyrimethamine and leucovorin (B II), but not evaluated in children </li></ul><ul><li>Adults – atovaquone: 1,500 mg orally twice daily plus pyrimethamine and leucovorin (C III), but not evaluated in children </li></ul><ul><li>Limited use of corticosteroids as adjuvant therapy with CNS disease </li></ul>
  32. 32. Cryptosporidiosis/Microsporidiosis Epidemiology <ul><li>Protozoal parasites that cause enteric illness in humans and animals </li></ul><ul><li>Human infection primarily caused by C hominis , C parvum , C meleagridis </li></ul><ul><li>Microsporida include E bieneusi and E intestinalis </li></ul><ul><li>Infection results from ingestion of oocysts excreted in feces of humans or animals </li></ul><ul><li>Invade intestinal tract mucosa causing watery, nonbloody diarrhea, dehydration, malnutrition </li></ul>
  33. 33. Cryptosporidiosis/Microsporidiosis Clinical Manifestations <ul><li>Frequent watery, nonbloody diarrhea </li></ul><ul><li>Abdominal cramps, fatigue, vomiting, anorexia, weight loss, poor weight gain </li></ul><ul><li>Fever and vomiting more common in children </li></ul><ul><li>Liver involvement causes abdominal pain and elevated alkaline phosphatase </li></ul><ul><li>Less common – myositis, cholangitis, sinusitis, hepatitis, CNS disease </li></ul>
  34. 34. Cryptosporidiosis/Microsporidiosis Diagnosis <ul><li>Cryptosporidiosis </li></ul><ul><li>Concentrated stool samples to demonstrating oocysts </li></ul><ul><li>Evaluate at least 3 separate stool samples </li></ul>
  35. 35. Cryptosporidiosis/Microsporidiosis Diagnosis <ul><li>Microsporidiosis </li></ul><ul><li>Use thin smears of unconcentrated stool-formalin suspension or duodenal aspirates stained with trichrome or chemofluorescent agents </li></ul><ul><li>Consider endoscopy in all patients with diarrhea >2 months duration </li></ul><ul><li>PCR techniques still in research </li></ul>
  36. 36. Cryptosporidiosis/Microsporidiosis Treatment <ul><li>Immune restoration following antiretroviral treatment frequently results in clearing </li></ul><ul><li>Supportive care, hydration, electrolyte replenishment, nutritional supplements </li></ul><ul><li>Available treatment inconsistently effective </li></ul>
  37. 37. Cryptosporidiosis Treatment <ul><li>Nitazoxanide – effective for Cryptosporidium and Giardia lamblia (B I for children and C III for HIV-infected children) </li></ul><ul><li>Nitazoxanide dose – 100 mg orally twice daily for children 1-3 years; 200 mg twice daily for children 4-11 years </li></ul><ul><li>Limited data – paromomycin, azithromycin </li></ul>
  38. 38. Microsporidiosis Treatment <ul><li>Albendazole: 7.5 mg/kg orally twice daily; maximum dose 400 mg orally twice daily (A II) </li></ul><ul><li>Fumagillin: limited data for adults, no data for HIV-infected children </li></ul>
  39. 39. Mycobacterium tuberculosis Epidemiology <ul><li>15,000 new cases of tuberculosis in United States in 2002 (6% among children <15 years of age) </li></ul><ul><li>Number of these that were HIV infected is uncertain </li></ul><ul><li>Incidence of TB in HIV-infected children 100 times higher than in uninfected </li></ul><ul><li>In South Africa, as many as 48% of children with TB were coinfected with HIV </li></ul>
  40. 40. <ul><li>Extrapulmonary and miliary TB more common in children <4 years old </li></ul><ul><li>Congenital TB has been reported </li></ul><ul><li>Drug-resistant TB can be transmitted </li></ul><ul><li>Patients should be treated under assumption that drug resistance profiles of source and patient are similar </li></ul>Mycobacterium tuberculosis Epidemiology
  41. 41. Mycobacterium tuberculosis Clinical Manifestations <ul><li>Younger children progress more rapidly (possibly due to delayed diagnosis) </li></ul><ul><li>Nonspecific symptoms: fever, weight loss, failure to thrive </li></ul><ul><li>Pulmonary TB most likely appears as infiltrate with hilar adenopathy </li></ul><ul><li>Clinical presentation of TB similar in HIV-positive and HIV-negative children </li></ul><ul><li>Extrapulmonary: marrow, lymph node, bone, pleura, pericardium, peritoneal </li></ul>
  42. 42. Mycobacterium tuberculosis Diagnosis <ul><li>Difficult to diagnose; maintain a degree of suspicion </li></ul><ul><li>M tuberculosis detected in up to 50% of gastric aspirate in non-HIV-infected children (obtain 3 consecutive morning gastric aspirates) </li></ul><ul><li>Usually requires linking TB in child to contact along with + radiograph, + skin test (TST) or PE </li></ul>
  43. 43. Mycobacterium tuberculosis Diagnosis <ul><li>About 10% of culture-positive children have negative TST </li></ul><ul><li>Perform annual TST beginning at 3-12 months using 5 TU PPD intradermally </li></ul><ul><li>DNA and RNA PCR not fully evaluated </li></ul>
  44. 44. Mycobacterium tuberculosis Treatment <ul><li>Treatment principles similar in HIV-positive and HIV-negative children </li></ul><ul><li>Initiate treatment as soon as possible in children <4 years old with suspected TB </li></ul><ul><li>Begin TB treatment 4-8 weeks before ARVs (B III) </li></ul><ul><li>If already on ARV, review drug interactions </li></ul><ul><li>Use of DOT increases adherence, decreases resistance, treatment failure, and relapse </li></ul>
  45. 45. Mycobacterium tuberculosis Treatment <ul><li>Initial treatment (induction phase) </li></ul><ul><li>4 drugs: isoniazid, rifampin, pyrazinamide, plus either ethambutol or streptomycin (A I) </li></ul><ul><li>Use ethionamide as alternative to ethambutol for CNS disease (A III) </li></ul>
  46. 46. Mycobacterium tuberculosis Treatment <ul><li>If clinical response occurs and organism is susceptible to isoniazid, discontinue ethambutol after 2 months </li></ul><ul><li>If severe disease, treat for 9-12 months </li></ul><ul><li>If multidrug resistance is found, treat with expert consultation </li></ul>
  47. 47. Mycobacterium tuberculosis Treatment <ul><li>Isoniazid </li></ul><ul><li>Dosage: 10-15 mg/kg orally once daily (maximum 300 mg daily) </li></ul><ul><li>Hepatic toxicity increases with rifampin </li></ul><ul><li>Peripheral neuritis, mild CNS toxicity, gastric upset </li></ul>
  48. 48. Mycobacterium tuberculosis Treatment <ul><li>Rifampin </li></ul><ul><li>Dosage: 10-20 mg/kg orally once daily (maximum 600 mg daily) </li></ul><ul><li>Side effects include rash; hepatitis; jaundice; GI upset; orange coloring of urine, tears, sweat </li></ul><ul><li>Rifampin can accelerate clearance of protease inhibitors (except ritonavir) and NNRTIs </li></ul>
  49. 49. Mycobacterium tuberculosis Treatment <ul><li>Rifabutin (B III) </li></ul><ul><li>Dosage: 10-20 mg/kg orally once daily </li></ul><ul><li>Limited data in children </li></ul><ul><li>Peripheral leukopenia, elevated liver enzymes, pseudojaundice, GI upset </li></ul>
  50. 50. Mycobacterium tuberculosis Treatment <ul><li>Rifabutin </li></ul><ul><li>Increases hepatic metabolism of certain protease inhibitors: reduce rifabutin dosage by 50% when given with ritonavir, indinavir, nelfinavir, amprenavir </li></ul><ul><li>Increase dosage of rifabutin by 50-100% when given with efavirenz </li></ul>
  51. 51. Mycobacterium tuberculosis Treatment <ul><li>Pyrazinamide </li></ul><ul><li>Dosage: 10-15 mg/kg orally once daily (maximum 2 g daily) </li></ul><ul><li>Hepatic toxicity, rash, arthralgia, GI upset </li></ul><ul><li>Ethambutol </li></ul><ul><li>Dosage: 15-25 mg/kg orally daily (maximum 1 g daily) </li></ul><ul><li>Toxicity includes optic neuritis, rash, nausea </li></ul>
  52. 52. Mycobacterium tuberculosis Treatment <ul><li>Secondary drugs </li></ul><ul><li>Ethionamide: 15-20 mg/kg orally divided into 2 or 3 doses daily </li></ul><ul><li>Streptomycin: 20-40 mg/kg daily intramuscularly (maximum dosage 1 g daily) </li></ul><ul><li>Alternatives: kanamycin, amikacin, capreomycin, quinolones, cycloserine, paraaminosalicylic acid </li></ul><ul><li>Steroids may be indicated for TB meningitis </li></ul>
  53. 53. Mycobacterium avium Complex Epidemiology <ul><li>Multiple related species of nontuberculosis mycobacteria: M avium , M intracellulare , M paratuberculosis </li></ul><ul><li>Second most common opportunistic infection in children </li></ul><ul><li>Acquired by means of innovation, ingestion, or inoculation </li></ul>
  54. 54. Mycobacterium avium Complex Epidemiology <ul><li>72% of children with isolated pulmonary MAC develop disseminated MAC by 8 months </li></ul><ul><li>May appear as isolated lymphadenitis </li></ul><ul><li>Frequency increases with age and declining CD4 T-cell count </li></ul><ul><li>CD4 T-cell risk factor for occurrence: </li></ul><ul><ul><li><750 mL <1 year; <500 mL 1-2 years; <75 mL 2-6 years; <50 mL >6 years </li></ul></ul>
  55. 55. Mycobacterium avium Complex Clinical Manifestations <ul><li>Recurrent fever, weight loss, failure to thrive, neutropenia, night sweats, chronic diarrhea, malabsorption, abdominal pain </li></ul><ul><li>Lymphadenopathy, hepatomegaly, splenomegaly </li></ul><ul><li>Respiratory symptoms uncommon among children </li></ul><ul><li>Laboratory abnormalities include anemia, leukopenia, and thrombocytopenia </li></ul>
  56. 56. Mycobacterium avium Complex Diagnosis <ul><li>Isolation of organism from biopsy, blood, bone marrow, lymph node, or other tissue </li></ul><ul><li>Histology demonstrating macrophage containing acid fast bacilli strongly indicates MAC </li></ul><ul><li>Culture is essential for differentiating from TB </li></ul><ul><li>Isolation from stool or respiratory does not necessarily indicate invasive disease </li></ul>
  57. 57. Mycobacterium avium Complex Treatment <ul><li>Preserve immune function through optimal treatment of HIV infection </li></ul><ul><li>Consider delaying initiation of ART for 1-2 weeks to avoid immune reconstitution syndrome </li></ul><ul><li>Initiate treatment with clarithromycin or azithromycin plus ethambutol (A I) </li></ul><ul><li>Consider rifabutin as third drug with severely ill patients (A I) </li></ul>
  58. 58. Mycobacterium avium Complex Treatment <ul><li>Note cautions in use of these drugs with ART </li></ul><ul><li>If rifabutin cannot be used, consider ciprofloxacin, levofloxacin, amikacin, streptomycin </li></ul><ul><li>Lifelong suppressive therapy required after initial therapy </li></ul>
  59. 59. Mycobacterium avium Complex Treatment <ul><li>Clarithromycin: 7.5-15 mg/kg orally twice daily (maximum 500 mg twice daily) (A I) </li></ul><ul><li>Azithromycin: 10-12 mg/kg once daily (maximum 500 mg daily) (A II) </li></ul><ul><li>Ethambutol: 15-25 mg/kg single oral dose (maximum 1 g) (A I) </li></ul>
  60. 60. Mycobacterium avium Complex Treatment <ul><li>Rifabutin: 10-20 mg/kg orally once daily (maximum 300 mg daily) (A I) </li></ul><ul><li>Ciprofloxacin: 20-30 mg/kg intravenously or orally once daily (maximum 1.5 g) </li></ul><ul><li>Amikacin: 15-30 mg/kg/day intravenously divided every 12-24 hours (maximum 1.5 g) (C III) </li></ul>
  61. 61. Pneumocystis jiroveci ( carinii ) Epidemiology <ul><li>Antibody in 80% of normal children by 4 years </li></ul><ul><li>Most common AIDS indicator disease in children </li></ul><ul><li>Incidence highest in first year of life, peaking at 3-6 months </li></ul><ul><li>Accounted for 57% of AIDS-defining illnesses in infants age <1 year pre-HAART </li></ul><ul><li>CD4 T-cell count not a good indicator of risk in infants <1 year old </li></ul><ul><li>Infection now unusual due to routine prophylaxis with trimethoprim/sulfamethoxazole </li></ul>
  62. 62. Pneumocystis jiroveci ( carinii ) Clinical Manifestations <ul><li>Fever, tachypnea, cough, dyspnea, poor feeding, weight loss </li></ul><ul><li>Abrupt or insidious onset </li></ul><ul><li>Bibasilar rales with evidence of hypoxia and respiratory distress </li></ul><ul><li>Extrapulmonary locations – spleen, liver,colon, pancreas, ear, eye, GI tract, bone marrow, heart, kidney, lymph nodes, CNS </li></ul>
  63. 63. Pneumocystis jiroveci ( carinii ) Diagnosis <ul><li>Hypoxia with low arterial oxygen pressure (alveolar-arterial oxygen gradient >30 mm/Hg) </li></ul><ul><li>Definitive diagnosis requires demonstrating organism </li></ul><ul><li>Induced sputum (difficult <2 years) </li></ul><ul><li>Bronchoscopy with bronchoalevolar lavage </li></ul><ul><li>Fiberoptic bronchoscopy with biopsy – generally not recommended </li></ul>
  64. 64. Pneumocystis jiroveci ( carinii ) Diagnosis <ul><li>Open lung biopsy most sensitive </li></ul><ul><li>Requires thorachotomy, chest tube drainage </li></ul><ul><li>Organisms seen on biopsy with: </li></ul><ul><ul><li>Gomori’s methenamine silver stain </li></ul></ul><ul><ul><li>Toluidine blue stain </li></ul></ul><ul><ul><li>Giemsa or Wright’s stain </li></ul></ul><ul><ul><li>Monoclonal antibody </li></ul></ul><ul><li>DNA PCR in fluids, lavage – mostly research </li></ul>
  65. 65. Pneumocystis jiroveci ( carinii ) Treatment <ul><li>Trimethoprim/sulfamethoxazole (TMP/SMX) (A I) </li></ul><ul><li>>2 months 15-20 mg/kg/day of TMP component intravenously in 3-4 divided doses </li></ul><ul><li>Infuse over course of 1 hour </li></ul><ul><li>Administer for 21 days </li></ul><ul><li>Can be given orally in children with mild to moderate disease </li></ul><ul><li>Lifelong prophylaxis indicated </li></ul>
  66. 66. Pneumocystis jiroveci ( carinii ) Treatment <ul><li>Adverse reactions: </li></ul><ul><ul><li>Rash </li></ul></ul><ul><ul><li>Stevens-Johnson syndrome (rare) </li></ul></ul><ul><ul><li>Neutropenia, thrombocytopenia, megaloblastic or aplastic anemia </li></ul></ul>
  67. 67. Pneumocystis jiroveci ( carinii ) Treatment <ul><li>Pentamidine isothionate </li></ul><ul><li>Recommended for patients intolerant of TMP/SMX or clinical failure with TMP/SMX (A I); do not combine use </li></ul><ul><li>4 mg/kg/day intravenously once daily over 60-90 minutes </li></ul><ul><li>Consider oral atovaquone after 7-10 days (B III) </li></ul>
  68. 68. Pneumocystis jiroveci ( carinii ) Treatment Alternatives <ul><li>Atovaquone (B I) </li></ul><ul><li>Limited data in children </li></ul><ul><li>30-40 mg/kg/day divided into 2 doses, given with fatty foods </li></ul><ul><li>Infants 3-24 months may require 45 mg/kg/day divided into 2 doses, given with fatty foods (A II) </li></ul><ul><li>Adverse reactions include rash, nausea, diarrhea, increased liver enzymes </li></ul>
  69. 69. Pneumocystis jiroveci ( carinii ) Treatment Alternatives <ul><li>Clindamycin/primaquine </li></ul><ul><li>Used for mild to moderate PCP in adults – no data in children (C III) </li></ul><ul><li>Primaquine contraindicated in G6PD deficiency </li></ul>
  70. 70. Pneumocystis jiroveci ( carinii ) Treatment Alternatives <ul><li>Clindamycin/primaquine </li></ul><ul><li>Pediatric clindamycin dosing based on other uses: 20-40 mg/kg/day intravenously divided into 3 or 4 doses, administered for 21 days </li></ul><ul><li>Primaquine dosing based on malaria: 0.3 mg/kg daily of the base, administered orally for 21 days </li></ul><ul><li>Adverse reactions include rash, nausea, diarrhea, pseudomembraneous colitis </li></ul>
  71. 71. Pneumocystis jiroveci ( carinii ) Treatment Alternatives <ul><li>Trimetrexate glucuronate plus leucovorin (folinic acid) </li></ul><ul><li>Used for severe PCP in adults – limited data in children (C III) </li></ul><ul><li>Trimetrexate – 45 mg/m 2 for 21 days </li></ul><ul><li>Leucovorin – 20 mg/m 2 every 6 hours for 24 days </li></ul>
  72. 72. Pneumocystis jiroveci ( carinii ) Treatment Alternatives <ul><li>Dapsone/trimethoprim </li></ul><ul><li>Use for mild to moderate PCP in adults – no data in children (C III) </li></ul><ul><li>Dapsone dose <13 years 2 mg/kg/day orally once daily (A II) for 21 days </li></ul><ul><li>Trimethoprim Isolationg/kg/day orally divided into 3 daily doses for 21 days </li></ul><ul><li>Adverse reactions include rash, anemia, thrombocytopenia, increased liver enzymes </li></ul>
  73. 73. Pneumocystis jiroveci ( carinii ) Treatment <ul><li>Corticosteroids </li></ul><ul><li>Consider use in moderate to severe PCP </li></ul><ul><li>Use within 72 hours of diagnosis </li></ul><ul><li>Results in reduced respiratory failure, decreased ventilation requirements, and decreased mortality </li></ul>
  74. 74. Pneumocystis jiroveci ( carinii ) Treatment <ul><li>Corticosteroids </li></ul><ul><li>Dosing recommendations vary </li></ul><ul><ul><li>Prednisone: 40 mg twice daily for 1-5 days; 40 mg once daily days 6-10; 20 mg once daily days 11-21 </li></ul></ul><ul><ul><li>Alternative: prednisone 1 mg/kg twice daily days 1-5; 0.5 mg/kg twice daily days 6-10; 0.5 mg/kg once daily days 11-21 </li></ul></ul>
  75. 75. Candida Infections Epidemiology <ul><li>Most common fungal infections in HIV-infected children </li></ul><ul><li>Thrush and diaper dermatitis occur in 50-85% of HIV-infected children </li></ul><ul><li>Pre-HAART era oropharyngeal candidiasis found in 94% of children with Candida esophagitis </li></ul><ul><li>Disseminated candidiasis rare in children except those with CMV, HSV coinfection or with central venous catheter </li></ul>
  76. 76. Candida Infections Epidemiology <ul><li>A substantial percentage of children with fungemia receive oral systemically absorbable azole antifungals, e.g., ketoconazole </li></ul><ul><li>Complications include disseminated infection of bone, liver, and kidney; endophthalmitis </li></ul><ul><li>Mortality >90% from disseminated candidiasis in children with fever and symptoms >14 days </li></ul>
  77. 77. Candida Infections Clinical Manifestations <ul><li>Thrush and erythematous, hyperplasic, and angular cheilitis </li></ul><ul><li>Esophageal candidiasis may present with odynophagia, dysphagia, or retrosternal pain </li></ul><ul><li>Children may develop nausea, vomiting, or weight loss and dehydration </li></ul><ul><li>New onset of fever in individuals with central venous catheters </li></ul><ul><li>Systemic fungemia may lead to endophthalmitis </li></ul>
  78. 78. Candida Infections Diagnosis <ul><li>Culture and KOH preparation with microscopic demonstration of budding yeast cells in wet mounts or biopsy </li></ul><ul><li>Blood culture using lysis centrifugation </li></ul><ul><li>“ Cobblestone” appearance on barium swallow </li></ul><ul><li>Perform endoscopy in refractory cases to look for CMV, HSV, MAC coinfections </li></ul>
  79. 79. Candida Infections Treatment <ul><li>Treat early uncomplicated oropharyngeal candidiasis (OPC) with topical therapy </li></ul><ul><li>Cotrimoxazole: 10 mg troches 4-5 times/day for 2 weeks (B II) </li></ul><ul><li>Nystatin suspension: 4-6 mL (400,000-600,000 units/mL) 4 times/day </li></ul><ul><li>Amphotericin B suspension: (100 mg/mL) 1 mL 4 times/day </li></ul>
  80. 80. Candida Infections Treatment <ul><li>Oral systemic therapy for OPC </li></ul><ul><li>Fluconazole: 3-6 mg/kg orally once daily for 7-14 days (A I) </li></ul><ul><li>Itraconazole: 2.5 mg/kg orally twice daily for 7-14 days (A I) </li></ul><ul><li>Ketoconazole: 5-10 mg/kg/day orally divided into 2 doses given for 14 days (D II) </li></ul><ul><li>Amphotericin oral suspension or IV for OPC refractory to other treatment </li></ul>
  81. 81. Candida Infections Treatment <ul><li>Esophageal disease </li></ul><ul><li>Treat both diagnosed esophageal disease and children with OPC and esophageal symptoms </li></ul><ul><li>Initiate treatment with: </li></ul><ul><ul><li>Fluconazole 6 mg/kg/day orally or intravenously on day 1 followed by 3-6 mg/kg for 14-21 days (A I) </li></ul></ul><ul><ul><li>Itraconazole oral solution 2.5 mg/kg/dose given twice daily or 5 mg/kg once daily for 14-21 days (A I) </li></ul></ul><ul><li>Consider low-dose IV amphotericin B minimum of 7 days for refractory disease (B II) </li></ul>
  82. 82. Candida Infections Treatment <ul><li>Esophageal disease </li></ul><ul><li>Other therapies not fully evaluated in children </li></ul><ul><li>Voriconazole: loading dose of 6 mg/kg intravenously every 12 hours on day 1, followed by 4 mg/kg every 12 hours thereafter; after stabilization, change to oral dosing </li></ul><ul><li>Caspofungin: available only in IV form; <50 kg dosage range 0.8-1.6 mg/kg daily; >50 kg, adult dosing </li></ul>
  83. 83. Candida Infections Treatment <ul><li>Invasive disease </li></ul><ul><li>Remove central venous catheter </li></ul><ul><li>Amphotericin B (A I) </li></ul><ul><ul><li>0.5-1.5 mg/kg once daily intravenously over 1-2 hours, administered in 5% dextrose at final concentration of 0.1 mg/mL </li></ul></ul><ul><ul><li>For mild to moderate disease, begin at 0.25-0.5 mg/kg and increase as tolerated to 1.5 mg/kg </li></ul></ul><ul><ul><li>Once stabilized, administer 1.5 mg/kg every other day (B III) </li></ul></ul><ul><ul><li>Treat for 3 weeks after last positive blood culture of symptoms </li></ul></ul>
  84. 84. Candida Infections Treatment <ul><li>Invasive disease: alternative therapy </li></ul><ul><li>Fluconazole in stable patients with uncomplicated candidemia without previous azole treatment (identification of Candida species essential; C krusei and C glabrata are resistant) (E III) </li></ul><ul><li>Amphotericin lipid formulations (limited pediatric experience) </li></ul><ul><ul><li>Amphotericin lipid complex (ABLC, Abelcet) </li></ul></ul><ul><ul><li>Liposomal amphotericin lipid complex (AmBisome) </li></ul></ul><ul><ul><li>Amphotericin B cholesteryl sulfate complex (ABCD) </li></ul></ul>
  85. 85. Candida Infections Treatment <ul><li>Amphotericin toxicity </li></ul><ul><li>Nephrotoxicity: azotemia, hypokalemia </li></ul><ul><li>Nephrotoxicity can be minimized by hydration with 0.9% saline intravenously 30 minutes prior to amphotericin B infusion </li></ul><ul><li>Infusion-related chills, fever, and vomiting; pretreat with acetaminophen or diphenhydramine </li></ul><ul><li>Rarely: hypotension, arrhythmias, neurotoxicity, hepatic toxicity </li></ul>
  86. 86. Candida Infections Treatment <ul><li>Fluconazole, itraconazole, ketoconazole toxicity </li></ul><ul><li>Inhibition of cytochrome P-450 dependent hepatic enzymes can result in either decreased levels of azole when administered with other drugs with hepatic metabolism or increased levels of other drugs with hepatic metabolism </li></ul><ul><li>Nausea, vomiting, rash, pruritis, Stevens-Johnson syndrome (rare), increased liver enzymes, hepatitis, leukopenia, anemia, hemolytic anemia, alopecia (fluconazole) </li></ul>
  87. 87. Cryptococcosis Epidemiology <ul><li>Low incidence of infection in children </li></ul><ul><li>Children usually infected during 6-12 age range </li></ul><ul><li>Usually severely immunosuppressed </li></ul>
  88. 88. Cryptococcosis Clinical Manifestations <ul><li>Meningoencephalitis most common manifestation </li></ul><ul><li>Fever, headache, altered mental status evolving over days to weeks </li></ul><ul><li>Acute illness with nuchal rigidity, seizures, focal neurologic signs observed in developing countries </li></ul><ul><li>Translucent, umbilicated, papules, nodules, ulcers, infiltrated plaques seen in disseminated disease </li></ul><ul><li>Pulmonary cryptococcosis unusual in children </li></ul>
  89. 89. Cryptococcosis Diagnosis <ul><li>Microscopic examination of CSF on India ink-stained wet mounts </li></ul><ul><li>Detection of cryptococcal antigen in CSF, serum, bronchoalevolar lavage fluid (can be negative in culture-positive meningitis) </li></ul><ul><li>Antigen levels useful in evaluating response to treatment and relapse </li></ul><ul><li>Pulmonary disease diagnosed by bronchoalevolar lavage and direct examination of India ink-stained specimens </li></ul>
  90. 90. Cryptococcosis Treatment <ul><li>Not well studied in children </li></ul><ul><li>Amphotericin B induction (0.7-1.5 mg/kg/day intravenously) combined with 2 weeks of flucytosine (25 mg/kg/dose given 4 times daily) until symptoms controlled (A I) </li></ul><ul><li>After symptoms are controlled, treat with fluconazole or itraconazole maintenance </li></ul><ul><li>Use amphotericin B alone if flucytosine is not tolerated </li></ul><ul><li>Fluconazole plus flucytosine is an alternate to amphotericin B (limited data in children) </li></ul>
  91. 91. Cryptococcosis Treatment <ul><li>Amphotericin toxicity </li></ul><ul><li>Nephrotoxicity: azotemia, hypokalemia </li></ul><ul><li>Nephrotoxicity can be minimized by hydration with 0.9% saline intravenously 30 minutes prior to amphotericin B infusion </li></ul><ul><li>Infusion-related chills, fever, and vomiting; pretreat with acetaminophen or diphenhydramine </li></ul><ul><li>Rarely: hypotension, arrhythmias, neurotoxicity, hepatic toxicity </li></ul>
  92. 92. Cryptococcosis Treatment <ul><li>Flucytosine toxicity </li></ul><ul><li>Bone marrow: anemia, leukopenia, thrombocytopenia </li></ul><ul><li>Liver, GI, and renal toxicity </li></ul>
  93. 93. Histoplasmosis Epidemiology <ul><li>Incidence of disseminated histoplasmosis in HIV-infected children in the United States <0.4% </li></ul><ul><li>Incidence is higher in countries such as Brazil, Argentina, and Mexico (2.7% to 3.8%) </li></ul><ul><li>No evidence of dissemination of maternal infection to the fetus or greater severity of infection during pregnancy </li></ul>
  94. 94. Histoplasmosis Clinical Manifestations <ul><li>Prolonged fever is the most common presentation </li></ul><ul><li>Malaise, weight loss, and nonproductive cough </li></ul><ul><li>Primary pulmonary focus leads to widespread dissemination in children </li></ul><ul><li>Physical findings include hepatosplenomegaly, erythematous nodular coetaneous lesions, CNS involvement with meningitis </li></ul><ul><li>Anemia, thrombocytopenia, elevated liver transaminases </li></ul>
  95. 95. Histoplasmosis Diagnosis <ul><li>Culture of Histoplasma for blood or other sources </li></ul><ul><li>Detection of H capsulatum polysaccharide antigen in urine, blood, CSF, or bronchoalevolar lavage using EIA assay </li></ul><ul><li>EIA sensitivity greater in disseminated disease or acute pulmonary disease; greater in urine than in serum </li></ul><ul><li>Antigen levels decline with treatment and correlate with both response to treatment and relapse </li></ul>
  96. 96. Histoplasmosis Diagnosis <ul><li>Antibody positive in most patients but not useful for diagnosis of acute infection </li></ul><ul><li>For diagnosis of CNS disease, a combination of CSF antibody, antigen, and culture is most sensitive </li></ul><ul><li>Skin testing not recommended for diagnosis </li></ul>
  97. 97. Histoplasmosis Treatment <ul><li>Limited data for children; recommendations based on adult data </li></ul><ul><li>Nonimmunocompromised not requiring hospitalization: </li></ul><ul><ul><li>Itraconazole dosage 6-8 mg/kg for 3-12 months (A II) </li></ul></ul><ul><ul><li>Alternative: fluconazole, but less effective and resistance can develop (C II) </li></ul></ul>
  98. 98. Histoplasmosis Treatment <ul><li>Amphotericin B for patients with severe disseminated disease requiring hospitalization and those who are immunocompromised </li></ul><ul><li>Amphotericin B induction dosage: 1 mg/kg for 4-6 weeks followed by itraconazole chronic suppressive therapy (A I) </li></ul><ul><li>After successful treatment of acute disease, use chronic lifelong suppressive therapy with itraconazole </li></ul><ul><li>Liposomal amphotericin B alternative in event of amphotericin B intolerance </li></ul>
  99. 99. Coccidioidomycosis Epidemiology <ul><li>Increased risk for infection with Coccidioides immitis among HIV-infected children in endemic areas (e.g., southwestern United States, northern Mexico, Central and South America) </li></ul><ul><li>Primary infection of newborn rare </li></ul><ul><li>In utero and perinatal transmission of C immitis reported </li></ul>
  100. 100. Coccidioidomycosis Clinical Manifestations <ul><li>Fever and dyspnea most common presentation </li></ul><ul><li>Chills, weight loss, lymphadenapaothy, chest pain, diffuse reticulonodular pulmonary infiltrates, meningitis </li></ul><ul><li>Disseminated disease associated with erythema multiforme; erythema nodosum; erythematous maculopapular rash; arthralgia; bone, joint, and CNS infection </li></ul>
  101. 101. Coccidioidomycosis Diagnosis <ul><li>Direct examination and culture of respiratory secretions and CSF or biopsy of lesions </li></ul><ul><li>Blood cultures positive in 15% of cases </li></ul><ul><li>IgM antibody detected by latex agglutination, EIA; immunodiffusion of tube precipitin appears early and indicates acute infection </li></ul>
  102. 102. Coccidioidomycosis Treatment <ul><li>Limited data in children; recommendations based on adult data </li></ul><ul><li>Treat diffuse pulmonary disease or disseminated disease with amphotericin B dosage of 0.5-1.5 mg/kg/day until clinical improvement occurs (A II) </li></ul><ul><li>Follow with chronic suppressive fluconazole or itraconazole therapy (A II) </li></ul><ul><li>Alterative therapy: fluconazole 5-6 mg/kg twice daily or itraconazole 4-10 mg/kg twice daily for 3 days followed by 2-5 mg/kg twice daily (B III) </li></ul>
  103. 103. Coccidioidomycosis Treatment <ul><li>CNS infection including meningitis </li></ul><ul><li>High-dose fluconazole 5-6 mg/kg twice daily </li></ul><ul><li>If unresponsive to fluconazole, use IV amphotericin B augmented by intrathecal amphotericin B (C I) </li></ul><ul><li>Surgical debridement or excision of localized persistent or resistant lesions in bone and lung may be helpful </li></ul>
  104. 104. Cytomegalovirus Epidemiology <ul><li>Infection with CMV common and often inapparent </li></ul><ul><li>50-80% of women of childbearing age in United States are CMV antibody positive </li></ul><ul><li>90% of HIV-infected women are CMV antibody positive </li></ul><ul><li>Infection occurs: </li></ul><ul><ul><li>During infancy, early childhood, adolescence </li></ul></ul><ul><ul><li>Via contact with virus containing salvia, urine, sexual fluid, blood, organ transplantation </li></ul></ul><ul><ul><li>Perinatally – most common </li></ul></ul>
  105. 105. Cytomegalovirus Epidemiology <ul><li>In utero infection occurs most commonly among infants born to mothers with primary infection during pregnancy </li></ul><ul><li>30-40% rate of CMV transmission to fetus following primary infection during pregnancy </li></ul><ul><li>0.2-1% rate of CMV transmission to fetus following recurrent infection during pregnancy (reactivation of infection or reinfection with a different strain of CMV) </li></ul>
  106. 106. Cytomegalovirus Epidemiology <ul><li>CMV may be transmitted intrapartum or postpartum </li></ul><ul><li>57% of infants whose mothers shed CMV become infected </li></ul><ul><li>53% of infants who are breast-fed with milk that contains CMV become infected </li></ul>
  107. 107. Cytomegalovirus Epidemiology <ul><li>HIV-coinfected women have a higher rate of CMV shedding </li></ul><ul><li>HIV-coinfected women have a higher rate of HIV transmission </li></ul><ul><li>HIV-infected children at greater risk of acquiring CMV during early childhood </li></ul><ul><li>CMV causes 8-10% of AIDS-defining illnesses </li></ul><ul><li>Children with positive CMV urine cultures have lower survival rates </li></ul>
  108. 108. <ul><li>10% of infants infected in utero are symptomatic at birth with congenital CMV syndrome </li></ul><ul><li>Infants with congenital infection: small for gestational age, purpura/petechiae, jaundice, hepatosplenomegaly, chorioretinitis, microcephaly, intracranial calcification, hearing loss </li></ul><ul><li>Delayed manifestations of congenital infections include developmental abnormalities, sensorineural hearing loss, chorioretinitis, neurologic defects </li></ul>Cytomegalovirus Clinical Manifestations
  109. 109. <ul><li>HIV-infected children with CMV coinfection have accelerated HIV progression </li></ul><ul><li>Coinfected children more likely to develop HIV CNS disease </li></ul><ul><li>CMV retinitis most frequent severe manifestation of CMV disease, accounting for 25% of CMV AIDS-defining illnesses </li></ul><ul><li>CMV retinitis is frequently asymptomatic </li></ul><ul><li>Older children may have floaters or loss of peripheral central vision </li></ul>Cytomegalovirus Clinical Manifestations
  110. 110. <ul><li>End organ disease reported in liver, lung, GI tract, pancreas, kidney, sinuses, CNS </li></ul><ul><li>Nonspecific symptoms include weight loss, loss of developmental milestones, fever, anemia, thrombocytopenia </li></ul><ul><li>Also observed: oral and esophageal ulcers, ascending cholangiopathy, CMV colitis, CMV pneumonia with shortness of breath and dry nonproductive cough </li></ul><ul><li>CNS manifestations include encephalopathy, myelitis, polyradiculopathy with nonspecific or normal CSF </li></ul>Cytomegalovirus Clinical Manifestations
  111. 111. <ul><li>Antibody assays indicative of maternal transfer of IgG in children <12 months; indicative of previous infection in children >12 months </li></ul><ul><li>Positive cell culture from urine, tissues, blood leukocytes </li></ul><ul><li>DNA PCR assays more sensitive than buffy coat or urine culture </li></ul><ul><li>Quantitative DNA PCR can be used to monitor disease and treatment </li></ul><ul><li>Other methods include monoclonal antibody staining and immunostaining for antigen </li></ul>Cytomegalovirus Diagnosis
  112. 112. <ul><li>Recommendations include: </li></ul><ul><li>Testing all HIV-infected infants with urine culture for CMV in the first months of life to identify congenital, perinatal, or early postnatal infection </li></ul><ul><li>Testing annually for CMV antibody in infants previously negative by culture and antibody to identify occult CMV infections permitting appropriate screening for retinitis </li></ul><ul><li>Dilated retinal examinations for coinfected children every 4-6 months; older children should report floaters and visual changes </li></ul>Cytomegalovirus Diagnosis
  113. 113. <ul><li>Symptomatic congenital CMV </li></ul><ul><li>Ganciclovir: 4-6 mg/kg intravenously every 12 hours for 6 weeks </li></ul><ul><li>Neutropenia may occur and may require dosage modification </li></ul>Cytomegalovirus Treatment
  114. 114. <ul><li>Initial treatment of disseminated CMV and retinitis </li></ul><ul><li>Ganciclovir: 5 mg/kg/dose intravenously over 1-2 hours twice daily for 14-21 days, followed by lifelong maintenance therapy (A I) </li></ul><ul><li>Resistance and myelosuppression can occur </li></ul><ul><li>Other toxic effects include renal impairment, CNS effects, GI dysfunction, increased liver enzymes </li></ul>Cytomegalovirus Treatment
  115. 115. <ul><li>Alternative treatment for ganciclovir resistance </li></ul><ul><li>Foscarnet (A I) at 60 mg/kg/dose intravenously (infused at 1 mg/kg/minute) over 1-2 hours every 8 hours for 14-21 days, followed by lifelong therapy </li></ul><ul><li>Foscarnet plus ganciclovir delays progression of retinitis in certain patients failing monotherapy </li></ul><ul><li>Toxicity: decreased renal function, metabolic abnormalities, electrolyte imbalances with secondary seizures, cardiac dysrhythmia, abnormal liver enzymes, and CNS symptoms </li></ul>Cytomegalovirus Treatment
  116. 116. <ul><li>Treatments for adults (inadequate pediatric data) </li></ul><ul><li>Valganciclovir: prodrug of ganciclovir, given orally, effective in retinitis in adults </li></ul><ul><li>Oral ganciclovir (or valganciclovir) plus ganciclovir sustained release intraocular implant used for retinitis </li></ul><ul><li>Cidofovir for retinitis </li></ul><ul><li>Fomivirsen: antisense nucleotide used as intravitreous injection </li></ul>Cytomegalovirus Treatment
  117. 117. Herpes Simplex Virus Epidemiology <ul><li>Neonatal HSV infection occurs at a rate of 1/2,000-5,000 deliveries </li></ul><ul><li>Transmitted from infected mother to infant primarily through exposure to maternal genital fluids during birth, by ascending infection, or by invasive procedures (e.g., fetal scalp electrodes) </li></ul><ul><li>Congenital (in utero) rare, but severe cutaneous, ocular, and CNS damage </li></ul>
  118. 118. Herpes Simplex Virus Epidemiology <ul><li>Maternal antibody to HSV predicts likelihood and severity of transmission to infant </li></ul><ul><li>Risk of neonatal HSV greatest in infant born to mother with primary HSV infection (30-40%) </li></ul><ul><li>Genital shedding of HSV and prolonged rupture of membranes increases risk of HSV transmission </li></ul><ul><li>Cesarean section lowers risk of transmission </li></ul>
  119. 119. Herpes Simplex Virus Epidemiology <ul><li>In United States, 75% of neonatal HSV caused by genital herpes (HSV 1 and 2) </li></ul><ul><li>HSV 2 seroprevalence in women of childbearing age is 26%; rates may be higher in HIV-infected women </li></ul><ul><li>HIV-infected women shed HSV from genital area more frequently than HIV-uninfected women (may be asymptomatic) </li></ul><ul><li>No evidence that in utero HSV infection is more frequent in HIV-infected pregnant women </li></ul>
  120. 120. Herpes Simplex Virus Clinical Manifestations <ul><li>Neonatal HSV may appear as: </li></ul><ul><li>Disseminated multiorgan disease (occurring in about 25% of neonates with infection) </li></ul><ul><li>Localized CNS disease (about 35%) </li></ul><ul><li>Localized infection of skin, eyes, mouth (about 40%) </li></ul>
  121. 121. Herpes Simplex Virus Clinical Manifestations <ul><li>Disseminated disease usually manifests at 9-11 days with encephalitis in 60-70% and vesicular rash in 60% </li></ul><ul><li>Localized disease usually appears at 10-11 days </li></ul><ul><li>Even with treatment, neonates with skin lesions may have recurrences for first 6 months of life </li></ul>
  122. 122. Herpes Simplex Virus Clinical Manifestations <ul><li>Outside neonatal period, most common presentation is orolabial disease with fever, irritability, submandibular lymphadenopathy, painful ulcers in gingival and oral mucosa (gingivostomatitis) </li></ul><ul><li>When severely immunocompromised, may develop disseminated HIV infection including infection of esophagus, CNS, liver, lung, kidney spleen, adrenal </li></ul>
  123. 123. Herpes Simplex Virus Diagnosis <ul><li>Appearance of typical ulcers and vesicles </li></ul><ul><li>Isolation of HSV from lesions following culture </li></ul><ul><li>Diagnosis of neonatal HSV based on cultures from blood, skin vesicles, mouth, eyes, urine, and stool </li></ul><ul><li>CSF using DNA PCR sequence common to HSV 1 and 2 </li></ul><ul><li>Direct immunofluorescence for HSV antigen in samples </li></ul><ul><li>HSV DNA PCR has replaced brain biopsy </li></ul>
  124. 124. Herpes Simplex Virus Treatment <ul><li>Acyclovir is the drug of choice regardless of infection status (oral and IV formulations available) </li></ul><ul><li>Treat neonatal HSV with 20 mg/kg/dose intravenously 3 times daily for 21 days for CNS and disseminated diseases </li></ul><ul><li>For skin, eye, mouth disease, treat for 14 days </li></ul><ul><li>Do not discontinue acyclovir in neonates with CNS disease unless CSF DNA PCR is negative at days 19-21 of treatment (B III) </li></ul>
  125. 125. Varicella-Zoster Virus Epidemiology <ul><li>9% of children <10 years old experience varicella infection (before vaccine use) </li></ul><ul><li>95% of adults have antibody to VZV </li></ul><ul><li>Rare perinatal VZV transmission </li></ul><ul><li>Congenital VZV occurs in 2% of infants whose mothers have primary VZV in first trimester </li></ul><ul><li>Zoster occurs only when previously VZV infected </li></ul><ul><li>Rate of zoster as high as 70% in HIV-infected children who are immunocompromised at time of primary VZV infection </li></ul>
  126. 126. Varicella-Zoster Virus Clinical Manifestations <ul><li>Congenital infection characterized by cicatricial skin scarring, limb hypoplasia, microcephaly, seizures, mental retardation, chorioretinitis, cataracts, microphthalmia, neurogenic bladder, hydroureter, abnormalities of swallowing </li></ul><ul><li>Duration of disease longer and complications more frequent in HIV-infected children </li></ul><ul><li>May experience chronic infection with continued new lesions for >1 month </li></ul><ul><li>May develop VZV retinitis </li></ul>
  127. 127. Varicella-Zoster Virus Diagnosis <ul><li>Clinical diagnosis based on typical generalized pruritic vesicular rash and fever </li></ul><ul><li>Direct immunofluorescence for VZV antigen on cells from skin, conjunctiva, mucosal lesions </li></ul><ul><li>VZV PCR sensitive and specific and can differentiate wild type from vaccine type </li></ul><ul><li>VZV antibody response positive 2-3 weeks after onset of illness – IgM indicates acute infection or recurrent infection </li></ul>
  128. 128. Varicella-Zoster Virus Treatment <ul><li>Acyclovir is the drug of choice for HIV-infected children; should be initiated as soon as possible after diagnosis (A I) </li></ul><ul><li>New lesions may continue to appear several days after initiation of treatment </li></ul><ul><li>Dosing </li></ul><ul><ul><li><1 year of age: 10 mg/kg/dose intravenously every 8 hours as 1-hour infusion for 7 days </li></ul></ul><ul><ul><li>>1 year of age: dose as above or 500 mg/m 2 /dose intravenously every 8 hours as 1-hour infusion for 7 days </li></ul></ul>
  129. 129. Varicella-Zoster Virus Treatment <ul><li>Children with HIV coinfection and normal or minimal decrease in CD4 T-cell counts </li></ul><ul><li>Acyclovir: 20 mg/kg per dose orally 4 times daily; maximum dose 800 mg (B III) </li></ul><ul><li>Children with zoster and HIV infection </li></ul><ul><li>Oral acyclovir </li></ul><ul><li>Use intravenously if severely immunocompromised, trigeminal nerve involvement or extensive multidermatomal zoster </li></ul>
  130. 130. Varicella-Zoster Virus Treatment <ul><li>Toxicities include phlebitis, nausea, vomiting, rash, impaired renal function, neutropenia </li></ul><ul><li>Oral acyclovir data limited in children <2 years of age; infants who receive long-term suppressive therapy (300 mg/kg/m 2 /dose administered 3 times daily) develop frequent neutropenia – usually self-limited </li></ul>
  131. 131. Varicella-Zoster Virus Treatment <ul><li>Use foscarnet for treatment of children with acyclovir-resistant VZV (B II) </li></ul><ul><li>Dosage: 40-60 mg/kg/dose intravenously over 1-2 hours administered 3 times daily for 7 days or until no new lesions appear </li></ul><ul><li>Modify dosage in patients with renal insufficiency </li></ul><ul><li>Valacyclovir and famciclovir alternative treatments (not active against acyclovir-resistant VZV) but no data in children </li></ul>
  132. 132. Human Papillomavirus Epidemiology <ul><li>HPV infects cutaneous and mucosal squamous epithelium </li></ul><ul><li>Approximately 100 distinct types </li></ul><ul><li>HPV 16, 18, 31, 33, and 35 are most often associated with intraepithelial malignancy </li></ul><ul><li>Genital HPV types can cause conjunctiva, nasal, oral, and laryngeal warts </li></ul><ul><li>Transmission occurs by direct contact or sexual contact (genital warts in young children may be a sign of sexual abuse) </li></ul>
  133. 133. Human Papillomavirus Epidemiology <ul><li>Latent HPV seen in 5-42% of pregnant women without HIV infection </li></ul><ul><li>HPV infection rates higher in HIV-positive women (up to 95%) </li></ul><ul><li>Mother-to-child HPV transmission occurs and can result in infant laryngeal and juvenile laryngeal papillomatosis </li></ul><ul><li>In general, no neonatal abnormalities are associated with detection of HPV in neonates </li></ul>
  134. 134. Human Papillomavirus Epidemiology <ul><li>HPV detected in 13-60% of sexually active adolescent girls </li></ul><ul><li>40-80% of infections in HIV uninfected are transient </li></ul><ul><li>Persistent infection with HPV 16, 81, 31, and 33 associated with high risk for developing cervical, vulvovaginal, and anal carcinoma; cervical and anal intraepithelial neoplasia </li></ul><ul><li>Increased risk if HIV infected </li></ul>
  135. 135. Human Papillomavirus Clinical Manifestations <ul><li>Hyperplasic, papillomatosis and verrucous squamous epithelial lesions on the skin and mucous membranes including anal, genital, oral, nasal, conjunctiva, GI, and respiratory tract mucosa </li></ul><ul><li>Lesions are soft, pink or white “cauliflower-like” sessile growths </li></ul>
  136. 136. Human Papillomavirus Diagnosis <ul><li>Most cutaneous and anogenital warts diagnosable on physical examination </li></ul><ul><li>Diagnosis of laryngeal papillomatosis requires laryngoscopy </li></ul><ul><li>DNA PCR can be used for detection of HPV types but not necessary for diagnosis or management of anogenital or cutaneous warts or papillomas </li></ul>
  137. 137. Human Papillomavirus Treatment <ul><li>Topical Treatment (B III) </li></ul><ul><li>Standard topical treatment often ineffective in HIV-infected children as underlying infection persists and results in recurrence </li></ul><ul><li>Podofilox 0.5% (antimitotic agent) </li></ul><ul><li>Imiquimod cream 5% (immune enhancer) </li></ul><ul><li>Trichloroacetic or bichloracetic acid 80-90% aqueous solution (caustic agent) </li></ul>
  138. 138. Human Papillomavirus Treatment <ul><li>Cidofovir topical gel 1% evaluated primarily in adults; used successfully for molluscum contagiosum in children with HIV infection </li></ul><ul><li>Cryotherapy and electrodessication applied to each lesion; treatment can be repeated every 1-2 weeks </li></ul><ul><li>Treatment of laryngeal papillomatosis directed primarily to removal of obstructions </li></ul><ul><li>ART not consistently associated with reduced risk for HPV-related cervical abnormalities </li></ul>
  139. 139. Hepatitis C Epidemiology <ul><li>Low seroprevalence in children in United States – 0.1-0.2% </li></ul><ul><li>Seroprevalence higher in HIV-infected children – 1.5% in one study </li></ul><ul><li>Risk for mother-to-infant transmission (MTCT) about 6% </li></ul><ul><li>Most infections occur at or near delivery </li></ul>
  140. 140. Hepatitis C Epidemiology <ul><li>Higher risk of MTCT if mother is HIV coinfected, IV drug user, or viremic; and with intrapartum exposure to infected blood, perineal or vaginal laceration, and fetal hypoxia </li></ul><ul><li>No reduction of transmission with Cesarean section </li></ul><ul><li>No increased risk from breast-feeding </li></ul><ul><li>Transmission risk of HIV may be increased with HCV coinfection </li></ul>
  141. 141. Hepatitis C Epidemiology <ul><li>Viremia in HCV-infected, HIV-uninfected children: persistent 52%; intermittent 42%; not detectable 6% </li></ul><ul><li>Spontaneous clearing has been reported in MTCT of HCV </li></ul><ul><li>>40% of those who are viremic have persistent features of hepatitis </li></ul>
  142. 142. Hepatitis C Clinical Manifestations <ul><li>Children have less frequent and slower progression than do adults </li></ul><ul><li>In a study of posttransfusion HCV, 55% of antibody-positive children had detectable HCV in blood </li></ul><ul><ul><li>1 child had abnormal liver enzymes </li></ul></ul><ul><ul><li>3/17 had histologic evidence of progressive liver damage after 21 years </li></ul></ul>
  143. 143. Hepatitis C Clinical Manifestations <ul><li>Histologic changes can be present in the absence of symptoms </li></ul><ul><li>No correlation between persistent viremia or elevated liver enzymes and liver disease </li></ul><ul><li>No evidence of clinical differences between HIV-coinfected and HIV-uninfected children </li></ul>
  144. 144. Hepatitis C Diagnosis <ul><li>HCV antibody passively transferred; not useful for diagnosis of infection until >18 months of age </li></ul><ul><li>Diagnosis confirmed using recombinant immunoblot assay (RIBA) </li></ul><ul><li>Infants <18 months use HCV RNA PCR (wait until >2 months of age) </li></ul><ul><li>If positive, repeat HCV RNA PCR </li></ul><ul><li>Liver biopsy best for evaluation of hepatic disease; should be considered before initiating treatment </li></ul>
  145. 145. Hepatitis C Treatment <ul><li>Administer hepatitis A vaccine </li></ul><ul><li>Consideration for treatment includes: symptomatic disease, advanced pathologic features (bridging necrosis, active cirrhosis) (B I) </li></ul><ul><li>Response to treatment better with HCV 2 and HCV 3 than with HCV 1 </li></ul><ul><li>Use quantitative HCV RNA to access treatment response </li></ul>
  146. 146. Hepatitis C Treatment <ul><li>Individuals with undetectable levels of HCV RNA following treatment should be retested after 24 weeks </li></ul><ul><li>In HIV-coinfected patients, testing can be continued for an additional 1-2 years </li></ul>
  147. 147. Hepatitis C Treatment <ul><li>Adults and children with HIV disease </li></ul><ul><li>Combination therapy with interferon (IFN) and ribavirin (A I) </li></ul><ul><li>Pegylated IFN alfa 2a: subcutaneously 180 mcg/kg weekly or alfa 2b subcutaneously 1.5 mcg/kg weekly (adults) </li></ul><ul><li>Ribavirin: 400 mg orally twice daily (adults) </li></ul><ul><li>Limited data on use of IFN in children </li></ul>
  148. 148. Hepatitis C Treatment – Children <ul><li>IFN alpha 2a and alpha 2b monotherapy most widely evaluated in children with HCV infection (not with HIV coinfection) </li></ul><ul><li>Pediatric dosage in studies ranged from 1.75 to 5 million units/m 2 (maximum dosage 3-5 million units) administered subcutaneously or intramuscularly 3 times weekly for 4-12 months </li></ul><ul><li>Treatment contraindicated in decompensated liver disease, cytopenia, cardiac disease or autoimmune disease </li></ul>
  149. 149. Hepatitis C Treatment – Children <ul><li>Ribavirin oral solution used in combination with IFN alfa </li></ul><ul><li>Dosage: oral solution 40 mg/mL – 15 mg/kg/day divided into 2 doses given twice daily </li></ul><ul><li>25-36 kg: 1 200 mg capsule in a.m., 1 in p.m. 37-49 kg: 1 200 mg capsule in a.m., 2 in p.m. 50-61 kg: 2 200 mg capsules in a.m., 2 in p.m. </li></ul>
  150. 150. Hepatitis C Treatment – Children <ul><li>Use IFN monotherapy when ribavirin cannot be used, e.g., unstable cardiopulmonary disease, severe anemia, hemoglobinopathy (B III) </li></ul><ul><li>Treat HCV 1 for 48 weeks; treat HCV 2, HCV 3 for 24 weeks; some treat HIV-coinfected patients for 48 weeks </li></ul>
  151. 151. Hepatitis C Treatment <ul><li>Adverse effects – IFN alfa </li></ul><ul><li>Flulike syndrome most severe during first month of therapy, consisting of fever, chills, headache, myalgia, arthalgia, abdominal pain, nausea, vomiting </li></ul><ul><li>Epistaxis associated with thrombocytopenia or prolonged prothrombin time </li></ul><ul><li>Neutropenia, anemia, thrombocytopenia </li></ul><ul><li>Personality changes </li></ul><ul><li>Abnormalities of thyroid function </li></ul>
  152. 152. Hepatitis C Treatment <ul><li>Adverse effects – ribavirin </li></ul><ul><li>Flulike syndrome consisting of fever, chills, headache, myalgia, arthalgia, abdominal pain, nausea, vomiting </li></ul><ul><li>Hemolytic anemia, lymphopenia </li></ul><ul><li>Neutropenia, anemia, thrombocytopenia </li></ul><ul><li>Depression and suicidal ideation </li></ul><ul><li>Do not use in combination with didanosine </li></ul>
  153. 153. Hepatitis B Epidemiology <ul><li>Acquired by perinatal or mother-to-infant transmission </li></ul><ul><li>Unknown whether there is a greater risk of HBV transmission to infants from HIV-coinfected mothers </li></ul><ul><li>All infants born to HBV-infected mothers should receive HBV vaccine and HBV immune globulin (HBIG) within 12 hours of birth </li></ul><ul><li>Second dose of vaccine at 1-2 months of age </li></ul><ul><li>Test for antibody to HBsAg at 9-15 months of age; if negative, reimmunize </li></ul>
  154. 154. Hepatitis B Epidemiology <ul><li>HBV-infected household members may pose risk of infection </li></ul><ul><li>Infection occurs through contact with infected blood or body fluids and through sharing of objects such as toothbrushes </li></ul><ul><li>All infants previously unimmunized should receive routine childhood HBV vaccine </li></ul>
  155. 155. Hepatitis B Epidemiology <ul><li>HBV infection risk increased through sexual activity in adolescents who are HIV coinfected </li></ul><ul><li>Immunize HBV-susceptible adolescents </li></ul><ul><li>Risk of chronic HBV infection in children without HIV infection is inversely related to age at time of infection </li></ul>
  156. 156. Hepatitis B Clinical Manifestations <ul><li>Majority of children are asymptomatic </li></ul><ul><li>Children who are coinfected with HIV may have smoldering chronic infection along with lethargy, malaise, fatigue, and anorexia </li></ul><ul><li>Jaundice sometimes present with hepatosplenomegaly </li></ul>
  157. 157. Hepatitis B Clinical Manifestations <ul><li>Young children may experience a serum sickness-like illness consisting of asymmetrical arthropathy and skin lesions </li></ul><ul><li>Papular acrodermatitis and urticarial or purpuric skin lesions may occur </li></ul><ul><li>Aplastic anemia, polyarteritis nodosa, glomerulonephritis are occasionally seen </li></ul>
  158. 158. Hepatitis B Diagnosis <ul><li>HBsAg is the first detectible marker and precedes increase in liver enzymes </li></ul><ul><li>Anti-HBV core antibody (anti-HBc) appears 2 weeks after HBsAg and persists for life </li></ul><ul><li>Passively transferred anti-HBc present in infants up to 12 months of age </li></ul><ul><li>IgM anti-HBc highly specific for acute infection </li></ul>
  159. 159. Hepatitis B Diagnosis <ul><li>In self-limited infections, HBsAg is eliminated in 1-2 months </li></ul><ul><li>Anti-HBsAg during convalescence, indicating immunity to HBV </li></ul><ul><li>After recovery, both anti-HBs and anti-HBc are usually present </li></ul><ul><li>Following immunization, only anti-HBs develops </li></ul>
  160. 160. Hepatitis B Diagnosis <ul><li>Chronically infected individuals are persistently positive for HBsAg and anti-HBc beyond 24 weeks; anti-HBs not detectible </li></ul><ul><li>HBe antigen (HBeAg) correlates with viral replication, DNA polymerase activity, increased infectivity, increased severity of liver disease </li></ul><ul><li>HBV DNA can be detected in serum and blood mononuclear cells by PCR or branched DNA </li></ul><ul><li>Quantitative DNA assays may be useful for evaluating responses to treatment </li></ul>
  161. 161. Hepatitis B Diagnosis <ul><li>All pregnant women should be tested for HBV surface antigen (HBsAg) </li></ul><ul><li>Repeat test late in pregnancy for women at high risk for HBV infection </li></ul>
  162. 162. Hepatitis B Treatment <ul><li>Administer hepatitis A vaccine to susceptible children >2 years of age </li></ul><ul><li>Indications for treatment are the same in children coinfected with HBV and HIV: </li></ul><ul><ul><li>Evidence of ongoing viral replication as indicated by presence of detectible HBV DNA with or without HBeAg positivity for at least 6 moths </li></ul></ul><ul><ul><li>Persistent elevation of transaminases (2 times upper limit of normal) </li></ul></ul><ul><ul><li>Evidence of chronic hepatitis on liver biopsy (B II) </li></ul></ul>
  163. 163. Hepatitis B Treatment <ul><li>Correlates of successful treatment not well defined </li></ul><ul><li>Current correlates: improved liver histology, normalization of hepatic transaminases, decrease in HBV DNA levels, loss of e antigen with development of anti-HBe </li></ul><ul><li>No target HBV DNA level has been defined </li></ul>
  164. 164. Hepatitis B Treatment <ul><li>IFN alfa, lamivudine (3TC), and adefovir approved for treatment of HBV in adults </li></ul><ul><li>IFN alfa and 3TC approved for children </li></ul><ul><li>Some recommend IFN alfa monotherapy for HBV/HIV-coinfected patients not yet requiring ART (to decrease possibility of resistance to 3TC and adefovir) (C III) </li></ul><ul><li>Some recommend 3TC monotherapy for HBV/HIV-coinfected patients who require ART (B III) (similar for children) </li></ul>
  165. 165. Hepatitis B Treatment <ul><li>IFN alfa </li></ul><ul><li>Most widely studied for treatment of compensated HBV liver disease </li></ul><ul><li>Studies of HBV/HIV coinfection in children have not been performed </li></ul><ul><li>Dosage range in children for IFN alfa 2a or 2b: 3-10 million units/m 2 subcutaneously 3 times weekly for 3-12 months </li></ul><ul><li>Commonly used regimen is 5 million units/m 2 3 times weekly for 6 months </li></ul><ul><li>Prolonged and higher dosages improve responses </li></ul>
  166. 166. Hepatitis B Treatment <ul><li>Adverse effects – IFN alfa </li></ul><ul><li>Flulike syndrome most severe during first month of therapy, consisting of fever, chills, headache, myalgia, arthalgia, abdominal pain, nausea, vomiting </li></ul><ul><li>Epistaxis associated with thrombocytopenia or prolonged prothrombin time </li></ul>
  167. 167. Hepatitis B Treatment <ul><li>Adverse effects – IFN alfa </li></ul><ul><li>Neutropenia, anemia, thrombocytopenia </li></ul><ul><li>Personality changes </li></ul><ul><li>Abnormalities of thyroid function </li></ul><ul><li>Treatment contraindicated in decompensated liver disease, cytopenias, cardiac disease, and autoimmune disease </li></ul>
  168. 168. Hepatitis B Treatment <ul><li>Children who do not respond to IFN alfa may respond to IFN beta (C III) </li></ul><ul><li>IFN beta shares biologic functions but is antigenically different </li></ul><ul><li>Dose 5 million units/m 2 intramuscularly 3 times a week for 6 months </li></ul><ul><li>In some studies, 45% of children were HBV DNA negative 18 months after therapy completion; 50% normalized transaminases; 32% became anti-HBe antibody positive </li></ul>
  169. 169. Hepatitis B Treatment <ul><li>Lamivudine (3TC) </li></ul><ul><li>Preferred therapy for HIV-coinfected children with compensated chronic liver disease who require ARVs for HIV infection (B III) </li></ul><ul><li>Results in rapid decline in HBV DNA levels </li></ul><ul><li>Used for HBV HIV uninfected children but persistent virologic response rates are low </li></ul><ul><li>Used as both primary and secondary treatment in HBV-infected, HIV-negative children </li></ul><ul><li>Extended monotherapy treatment can lead to resistance </li></ul>
  170. 170. Hepatitis B Treatment <ul><li>Lamivudne (3TC) </li></ul><ul><li>Do not use 3TC monotherapy in HIV/HBV-coinfected children (3TC resistance develops) </li></ul><ul><li>Dosage: 3 mg/kg once daily (lower than that required for HIV) </li></ul><ul><li>If 3TC is used to treat HBV/HIV-coinfected children, treat with 4 mg/kg twice daily in the context of ARV combination therapy </li></ul>
  171. 171. Hepatitis B Treatment <ul><li>Adefovir </li></ul><ul><li>Some recommend combined adefovir or tenofovir in addition to 3TC as part of suppressive ART to reduce development of resistance </li></ul><ul><li>Continue 3TC along with ARVs in children who respond; exacerbations of HBV can occur when therapy is discontinued </li></ul><ul><li>Combination 3TC and IFN alfa not well studied </li></ul><ul><li>Adefovir dipivoxil (10 mg once daily in adults) active against HBV with minimal anti-HIV effect (insufficient data in children) </li></ul>
  172. 172. <ul><li>This presentation was prepared by Arthur Ammann, MD, for the AETC National Resource Center in April 2005. </li></ul><ul><li>See the AETC NRC Web site for the most current version of this presentation - http://www.aidsetc.org. </li></ul>About This Slide Set

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