1. Guidelines for Prevention and Treatment of Opportunistic Infections among HIV-Infected Children Fungal Infections Recommendations from Centers for Disease Control and Prevention, the National Institutes of Health, the HIV Medicine Association of the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the American Academy of Pediatrics

2. July 2009 2 www.aidsetc.org These slides were developed using the April 2008 Guidelines. The intended audience is clinicians involved in the care of patients with HIV. Users are cautioned that, because of the rapidly changing field of HIV care, this information could become out of date quickly. Finally, it is intended that these slides be used as prepared, without changes in either content or attribution. Users are asked to honor this intent. Expert opinion should be sought for complex treatment regimens. – AETC NRC About This Presentation

3. July 2009 3 www.aidsetc.org Aspergillosis: Epidemiology  Aspergillus species are ubiquitous molds found in soil, on plants, and in decomposing organic materials  The most common species causing aspergillosis are A fumigatus and A flavus  Rare but frequently lethal infection  Risk factors include low CD4 count, neutropenia, corticosteroids, concurrent malignancy with chemotherapy, HIV-related phagocytic impairment, previous respiratory infections, broad-spectrum antibiotic exposure

4. July 2009 4 www.aidsetc.org Aspergillosis: Clinical Manifestations  Pulmonary aspergillosis is the most common presentation  Invasive pulmonary aspergillosis associated with fever, cough, dyspnea, pleuritic pain  Additional manifestations include necrotizing tracheobronchitis, pseudomembranous tracheobronchitis, CNS involvement, cutaneous, sinus, middle ear and mastoid infection

5. July 2009 5 www.aidsetc.org Aspergillosis: Diagnosis  Usually isolated from the blood but also readily isolated from lung, sinus, brain, and skin biopsy  Definitive diagnosis includes histopathologic demonstration of organisms in biopsy specimens  Presumptive diagnosis of respiratory tract infection can be made if Aspergillus species is recovered from respiratory sample

6. July 2009 6 www.aidsetc.org Aspergillosis: Diagnosis (2)  Chest radiograph demonstrates either diffuse interstitial pneumonitis or localized wedge-shaped infiltrates  CT of chest may be used to identify a “halo” sign  Cavitation and air crescent formation in chest CDT more frequent in older children and adults

7. July 2009 7 www.aidsetc.org Aspergillosis: Prevention  Consider excluding plants and flowers from rooms and avoiding food items such as nuts and spices  Erect suitable barriers between patient care and construction sites, clean shower heads routinely as well as hot- water faucets and air-handling systems

8. July 2009 8 www.aidsetc.org Aspergillosis: Treatment  Voriconazole is recommended for treatment of invasive aspergillosis  Adult data indicate that voriconazole is superior to amphotericin B but data in children are limited  Recommended dosage for children is 6-8 mg/kg IV (or 8 mg/kg orally) Q12H, followed by 7 mg/kg IV or orally twice daily  Treatment is continued for 12 weeks

9. July 2009 9 www.aidsetc.org Aspergillosis: Adverse Effects and Treatment Failure  Voriconazole side effects include reversible dose-dependent visual disturbances, elevated liver enzymes, and occasional skin rash  Amphotericin toxicity is associated primarily with fever, chills, and nephrotoxicity  Efficacy of antifungal therapy for aspergillosis is poor  Experimental approaches include evaluation of caspofungin

10. July 2009 10 www.aidsetc.org Candida Infections: Epidemiology  Most common fungal infections in HIV-infected children  Thrush and diaper dermatitis occur in 50-85% of HIV-infected children  In pre-ART era, oropharyngeal candidiasis found in 94% of children with Candida esophagitis  Disseminated candidiasis rare in children except those with CMV or HSV coinfection, and those with central venous catheter

11. July 2009 11 www.aidsetc.org Candida Infections: Epidemiology (2)  A substantial percentage of children with fungemia receive oral, systemically absorbable azole antifungals (eg, ketoconazole)  Complications include disseminated infection of bone, liver, and kidney; endophthalmitis  Mortality from disseminated candidiasis >90% in children with fever and symptoms >14 days

12. July 2009 12 www.aidsetc.org Candida Infections: Clinical Manifestations  Thrush and erythematous, hyperplastic, and angular cheilitis  Esophageal candidiasis may present with odynophagia, dysphagia, or retrosternal pain  Children may develop nausea, vomiting, or weight loss and dehydration  New onset of fever in individuals with central venous catheters  Systemic fungemia may lead to endophthalmitis

13. July 2009 13 www.aidsetc.org Candida Infections: Diagnosis  Culture and KOH preparation with microscopic demonstration of budding yeast cells in wet mounts or biopsy  Blood culture using lysis centrifugation  “Cobblestone” appearance on barium swallow  Perform endoscopy in refractory cases to look for CMV, HSV, MAC coinfections  Research studies or evaluating detection of candidate antigens for early diagnosis

14. July 2009 14 www.aidsetc.org Candida Infections: Prevention  Routine primary prophylaxis of candidiasis in HIV-infected children is not indicated  Candida organisms are common commensals on mucosal surfaces in healthy individuals and no measures are available to reduce exposure

15. July 2009 15 www.aidsetc.org Candida Infections: Treatment Treat early uncomplicated oropharyngeal candidiasis (OPC) with topical therapy  Cotrimoxazole: 10 mg troches 4-5 times/day for 2 weeks (B II)  Nystatin suspension: 4-6 mL (400,000-600,000 units/mL) 4 times/day  Amphotericin B suspension: (100 mg/mL) 1 mL 4 times/day

16. July 2009 16 www.aidsetc.org Candida Infections: Treatment (2) Oral systemic therapy for OPC  Fluconazole: 3-6 mg/kg orally once daily for 7-14 days (A I)  Itraconazole: 2.5 mg/kg orally BID for 7-14 days (A I)  Ketoconazole: 5-10 mg/kg/day orally divided into 2 doses given for 14 days (D II)  Amphotericin oral suspension or IV for OPC refractory to other treatment

17. July 2009 17 www.aidsetc.org Candida Infections: Treatment (3) Esophageal disease  Treat both diagnosed esophageal disease and children with OPC and esophageal symptoms (A I)  Initiate treatment with:  Fluconazole 6 mg/kg/day orally or IV on day 1 followed by 3-6 mg/kg for 14-21 days (A I)  Itraconazole oral solution 2.5 mg/kg/dose given twice daily or 5 mg/kg once daily for 14-21 days (A I)  Consider low-dose IV amphotericin B minimum of 7 days for refractory disease (B II)

18. July 2009 18 www.aidsetc.org Candida Infections: Treatment (4) Esophageal disease  Other therapies not fully evaluated in children  Voriconazole: loading dose of 6 mg/kg IV Q12H on day 1, followed by 4 mg/kg Q12H thereafter; after stabilization, change to oral dosing  Caspofungin: available only in IV form; 50 kg, adult dosing

19. July 2009 19 www.aidsetc.org Candida Infections: Treatment (5) Invasive disease  Remove central venous catheter  Amphotericin B (A I)  0.5-1.5 mg/kg once daily IV over course of 1-2 hours, administered in 5% dextrose at final concentration of 0.1 mg/mL  For mild to moderate disease, begin at 0.25-0.5 mg/kg and increase as tolerated to 1.5 mg/kg  Once stabilized, administer 1.5 mg/kg every other day (B III)  Treat for 3 weeks after last positive blood culture of symptoms

20. July 2009 20 www.aidsetc.org Candida Infections: Treatment (6) Invasive disease: alternative therapy  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)  Amphotericin lipid formulations (limited pediatric experience)  Amphotericin lipid complex (ABLC, Abelcet)  Liposomal amphotericin lipid complex (AmBisome)  Amphotericin B cholesteryl sulfate complex (ABCD)

21. July 2009 21 www.aidsetc.org Candida Infections: Treatment (7) Treatment under development  Caspofungin, micafungin, and anidulafungin have been studied in battles with HIV infection, neutropenic children at risk of fungal infection in children with documented candidiasis  Data on HIV-infected children are limited

22. July 2009 22 www.aidsetc.org Candida Infections: Treatment (8) Amphotericin toxicity  Nephrotoxicity: azotemia, hypokalemia  Nephrotoxicity can be minimized by hydration with 0.9% saline intravenously 30 minutes before amphotericin B infusion  Infusion-related chills, fever, and vomiting; pretreat with acetaminophen or diphenhydramine  Rarely: hypotension, arrhythmias, neurotoxicity, hepatic toxicity

23. July 2009 23 www.aidsetc.org Candida Infections: Treatment (9) Fluconazole, itraconazole, ketoconazole toxicity  Inhibition of CYP450-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  Nausea, vomiting, rash, pruritus, Stevens-Johnson syndrome (rare), increased liver enzymes, hepatitis, leukopenia, anemia, hemolytic anemia, alopecia (fluconazole)

24. July 2009 24 www.aidsetc.org Candida Infections: Treatment Failure Oral pharyngeal and esophageal candidiasis  Initial failure should be treated with oral fluconazole, itraconazole, oral amphotericin B, or low-dose IV amphotericin B Invasive disease  Amphotericin B lipid formulations can be used for children who cannot tolerate amphotericin B, have disseminated Candida infection that is resistance to amphotericin B, or are at risk of nephrotoxicity

25. July 2009 25 www.aidsetc.org Coccidioidomycosis: Epidemiology  Increased risk of infection with Coccidioides immitis and Coccidioides posadasii among HIV-infected children in endemic areas (eg, southwestern United States, northern Mexico, Central and South America)  Primary infection of newborn rare  In utero and perinatal transmission of C immitis reported  Reports of infection in nonendemic areas usually due to reactivation

26. July 2009 26 www.aidsetc.org Coccidioidomycosis: Clinical Manifestations  Fever and dyspnea most common presentation  Chills, weight loss, lymphadenopathy, chest pain, diffuse reticulonodular pulmonary infiltrates, meningitis  Disseminated disease associated with erythema multiforme; erythema nodosum; erythematous maculopapular rash; arthralgia; bone, joint, and CNS infection

27. July 2009 27 www.aidsetc.org Coccidioidomycosis: Diagnosis  Direct examination and culture of respiratory secretions and CSF or biopsy of lesions  Blood cultures positive in 15% of cases  Complement fixation assay detects IgG antibody, positive IgM assays suggest active or recent infection, complement fixation titers > 1:16 correlate with presence and severity of extrapulmonary infection

28. July 2009 28 www.aidsetc.org Coccidioidomycosis: Prevention  Difficult to avoid exposure in endemic areas  Exposure can be reduced by avoiding activities that predispose to inhalation of spores such as disturbing contaminated soil, being outdoors during dust storms

29. July 2009 29 www.aidsetc.org Coccidioidomycosis: Treatment  Limited data in children; recommendations based on adult data  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)  Follow with chronic suppressive fluconazole or itraconazole therapy (A II)  Alterative therapy: fluconazole 5-6 mg/kg BID or itraconazole 4-10 mg/kg BID for 3 days followed by 2-5 mg/kg BID (B III)

30. July 2009 30 www.aidsetc.org Coccidioidomycosis: Treatment (2) CNS infection, including meningitis  High-dose fluconazole 5-6 mg/kg BID  If unresponsive to fluconazole, use IV amphotericin B augmented by intrathecal amphotericin B (C I)

31. July 2009 31 www.aidsetc.org Coccidioidomycosis: Monitoring, Adverse Events and Toxicity  Monitoring of complement fixing IgG antibody is useful  Toxicity of antifungal drugs includes fevers, chills, nausea and vomiting, nephrotoxicity  Interaction of all antifungal agents with ARVs should be investigated; fluconazole and itraconazole appear to be safe in combination with ARVs  Voriconazole should be avoided in patients on PIs or NNRTIs

32. July 2009 32 www.aidsetc.org Cryptococcosis: Epidemiology  Most infections caused by Cryptococcosis neoformans and Cryptococcosis gattii  Infection occurs primarily in tropical and subtropical areas  Low incidence of infection in children, especially with use of ART  Children usually infected during 6-12 year age range  Usually severely immunosuppressed

33. July 2009 33 www.aidsetc.org Cryptococcosis: Clinical Manifestations  Meningoencephalitis most common manifestation  Fever, headache, altered mental status evolving over days to weeks  Acute illness with nuchal rigidity, seizures, focal neurologic signs observed in developing countries  Translucent, umbilicated, papules, nodules, ulcers, infiltrated plaques seen in disseminated disease  Pulmonary cryptococcosis unusual in children

34. July 2009 34 www.aidsetc.org Cryptococcosis: Diagnosis  Microscopic examination of CSF on India ink-stained wet mounts  Detection of cryptococcal antigen in CSF, serum, bronchoalveolar lavage fluid (can be negative in culture-positive meningitis)  Fungal cultures from CSF, sputum, and blood cultures can identify the organism  Antigen levels useful in evaluating response to treatment and relapse  Pulmonary disease diagnosed by bronchoalveolar lavage and direct examination of India ink-stained specimens

35. July 2009 35 www.aidsetc.org Cryptococcosis: Prevention  No proven strategies to prevent exposure  Believed to be acquired by inhalation of aerosolized particles from the environment

36. July 2009 36 www.aidsetc.org Cryptococcosis: Treatment Not well studied in children; infection is often fatal in the absence of treatment CNS Disease  Amphotericin B induction (0.7-1.5 mg/kg/day IV) combined with 2 weeks of flucytosine (25 mg/kg/dose given 4 times daily) followed by fluconazole for a minimum of 8 weeks  After symptoms are controlled, treat with fluconazole or itraconazole maintenance  Use amphotericin B alone if flucytosine is not tolerated  Fluconazole plus flucytosine is an alternative to amphotericin B (limited data in children)

37. July 2009 37 www.aidsetc.org Cryptococcosis: Treatment (2) Pulmonary and extrapulmonary cryptococcosis  No clinical trials on the outcome of non-CNS cryptococcosis in HIV-infected patients  Treat with amphotericin B with or without the addition of fluconazole (A III)  Fluconazole or itraconazole should be continued long-term

38. July 2009 38 www.aidsetc.org Cryptococcosis: Monitoring and Drug Toxicity Amphotericin toxicity  Nephrotoxicity: azotemia, hypokalemia  Nephrotoxicity can be minimized by hydration with 0.9% saline intravenously 30 minutes before amphotericin B infusion  Infusion-related chills, fever, and vomiting; pretreat with acetaminophen or diphenhydramine  Rarely: hypotension, arrhythmias, neurotoxicity, hepatic toxicity

39. July 2009 39 www.aidsetc.org Cryptococcosis: Monitoring and Drug Toxicity (2) Flucytosine toxicity  Bone marrow: anemia, leukopenia, thrombocytopenia  Liver, GI, and renal toxicity Fluconazole toxicity  Potential interaction with ARV should be evaluated before initiating treatment (A III)

40. July 2009 40 www.aidsetc.org Cryptococcosis: IRIS and Treatment Failure  IRIS related to cryptococcosis can present within weeks  Optimal treatment of patients experiencing treatment failure has not been defined  Patients failing initial azole treatment should be switched to amphotericin B in combination with flucytosine  Consider use of liposomal amphotericin B  Experience with posaconazole or voriconazole is limited

41. July 2009 41 www.aidsetc.org Histoplasmosis: Epidemiology  Pathogen is Histoplasma capsulatum  Incidence of disseminated histoplasmosis in HIV-infected children in the United States is <0.4%  Incidence is higher in countries such as Brazil, Argentina, and Mexico (2.7% to 3.8%)  No evidence of dissemination of maternal infection to the fetus or greater severity of infection during pregnancy

42. July 2009 42 www.aidsetc.org Histoplasmosis: Clinical Manifestations  Prolonged fever is the most common presentation  Malaise, weight loss, and nonproductive cough  Primary pulmonary focus leads to widespread dissemination in children  Pulmonary manifestations common  Physical findings include hepatosplenomegaly, erythematous nodular coetaneous lesions, CNS involvement with meningitis  Anemia, thrombocytopenia, elevated liver transaminases  Progressive disseminated histoplasmosis (PDH) is fatal if untreated

43. July 2009 43 www.aidsetc.org Histoplasmosis: Diagnosis  Serologic testing using CF and immunodiffusion is insensitive in the presence of HIV infection.  Positive in most patients but not useful for diagnosis of acute infection  For diagnosis of CNS disease, a combination of CSF antibody, antigen, and culture is most sensitive  Skin testing not recommended for diagnosis

44. July 2009 44 www.aidsetc.org Histoplasmosis: Diagnosis (2)  Culture of Histoplasma from blood or other sources  Detection of H capsulatum polysaccharide antigen in urine, blood, CSF, or bronchoalveolar lavage using EIA  EIA sensitivity greater in disseminated disease or acute pulmonary disease; greater in urine than in serum  Antigen levels decline with treatment and correlate with both response to treatment and relapse

45. July 2009 45 www.aidsetc.org Histoplasmosis: Prevention  Most infections occur without a recognized history of exposure  Sites and conditions commonly implicated include outbreaks of soil contamination with bird or bat droppings, older urban and rural structures, and decaying vegetation

46. July 2009 46 www.aidsetc.org Histoplasmosis: Treatment  Limited data for children; recommendations based on adult data  PDH is fatal without treatment and should be treated with either amphotericin B or itraconazole  Fluconazole has been used successfully as an alternative for patients with mild disease and for those who cannot tolerate itraconazole

47. July 2009 47 www.aidsetc.org Histoplasmosis: Treatment (2)  Amphotericin B for patients with severe disseminated disease requiring hospitalization and for those who are immunocompromised  Amphotericin B induction dosage: 1 mg/kg for 4-6 weeks followed by itraconazole chronic suppressive therapy for 12 months (A I)  After successful treatment of acute disease, use chronic lifelong suppressive therapy with itraconazole  Liposomal amphotericin B alternative in event of amphotericin B intolerance

48. July 2009 48 www.aidsetc.org Histoplasmosis: Monitoring and Adverse Effects  Antigen levels should be monitored during treatment and for 1 year thereafter  Adverse effects of amphotericin B include nephrotoxicity, infusion related fever, chills, nausea, and vomiting  Azole drugs inhibit CYP450-dependent hepatic enzymes, warranting careful review of drug interactions when using ARVs

49. July 2009 49 www.aidsetc.org Pneumocystis jiroveci (carinii): Epidemiology  Organisms are found worldwide in the lungs of humans and lower animals  Antibody in 80% of normal children by 4 years  Most common AIDS indicator disease in children  Incidence highest in first year of life, peaking at 3-6 months  Accounted for 57% of AIDS-defining illnesses in infants age <1 year pre-ART  CD4 T-cell count not a good indicator of risk in infants <1 year old  Infection now unusual owing to routine prophylaxis with TMP-SMX

50. July 2009 50 www.aidsetc.org Pneumocystis jiroveci (carinii): Clinical Manifestations  Fever, tachypnea, cough, dyspnea, poor feeding, weight loss  Abrupt or insidious onset  Bibasilar rales with evidence of hypoxia and respiratory distress  Extrapulmonary locations: spleen, liver, colon, pancreas, ear, eye, GI tract, bone marrow, heart, kidney, lymph nodes, CNS

51. July 2009 51 www.aidsetc.org Pneumocystis jiroveci (carinii): Diagnosis  Hypoxia with low arterial oxygen pressure (alveolar-arterial oxygen gradient >30 mmHg)  Definitive diagnosis requires demonstrating organism  Induced sputum (difficult <2 years)  Bronchoscopy with bronchoalveolar lavage  Fiberoptic bronchoscopy with biopsy – generally not recommended

52. July 2009 52 www.aidsetc.org Pneumocystis jiroveci (carinii): Diagnosis (2)  Open lung biopsy most sensitive  Requires thoracotomy, chest tube drainage  Organisms seen on biopsy with:  Gomori methenamine silver stain  Toluidine blue stain  Giemsa or Wright stain  Monoclonal antibody  DNA PCR for Pneumocystis MSG gene in fluids, lavage – sensitive but less specific than histology

53. July 2009 53 www.aidsetc.org Pneumocystis jiroveci (carinii): Prevention  Need for isolation of hospitalized patients has not been demonstrated, but when prophylaxis cannot be given, may need to isolate patient or susceptible contacts  Infants born to HIV-infected mothers should be considered for prophylaxis at 4-6 weeks of age and continued until 1 year of age (A II)

54. July 2009 54 www.aidsetc.org Pneumocystis jiroveci (carinii): Prevention (2) Chemoprophylaxis with TMP-SMX recommended as follows, based on CD4 counts and patient age:  6 years: CD4 count <200 cells/µL or CD4 percentage <15%  1 to 5 years: CD4 count <500 cells/µL or CD4 percentage <15%  All HIV-infected infants <12 months of age regardless of CD4 count or percentage

55. July 2009 55 www.aidsetc.org Pneumocystis jiroveci (carinii): Treatment TMP-SMX (A I)  >2 months 15-20 mg/kg/day of TMP component IV in 3-4 divided doses  Infuse over course of 1 hour  Administer for 21 days  Can be given orally in children with mild to moderate disease  Lifelong prophylaxis indicated

56. July 2009 56 www.aidsetc.org Pneumocystis jiroveci (carinii): Treatment (2)  Adverse reactions:  Rash  Stevens-Johnson syndrome (rare)  Neutropenia, thrombocytopenia, megaloblastic or aplastic anemia

57. July 2009 57 www.aidsetc.org Pneumocystis jiroveci (carinii): Treatment (3) Pentamidine isethionate  Recommended for patients with intolerance to TMP-SMX or clinical failure with TMP-SMX (A I); do not combine use  4 mg/kg/day IV once daily over period of 60- 90 minutes  Consider oral atovaquone after 7-10 days (B III)

58. July 2009 58 www.aidsetc.org Pneumocystis jiroveci (carinii): Treatment Alternatives Atovaquone (B I)  Limited data in children  30-40 mg/kg/day divided into 2 doses, given with fatty foods  Infants 3-24 months may require 45 mg/kg/day divided into 2 doses, given with fatty foods (A II)  Adverse reactions include rash, nausea, diarrhea, increased liver enzymes

59. July 2009 59 www.aidsetc.org Pneumocystis jiroveci (carinii): Treatment Alternatives (2) Clindamycin/primaquine  Used for mild to moderate PCP in adults; no data in children (C III)  Primaquine contraindicated in G6PD deficiency

60. July 2009 60 www.aidsetc.org Pneumocystis jiroveci (carinii): Treatment Alternatives (3) Clindamycin/primaquine  Pediatric clindamycin dosing based on other uses: 20-40 mg/kg/day IV divided into 3 or 4 doses, administered for 21 days  Primaquine dosing based on malaria: 0.3 mg/kg daily of the base, administered orally for 21 days  Adverse reactions include rash, nausea, diarrhea, pseudomembranous colitis

61. July 2009 61 www.aidsetc.org Pneumocystis jiroveci (carinii): Treatment Alternatives (4) Dapsone/TMP  Use for mild to moderate PCP in adults; no data in children (C III)  Dapsone dosage <13 years 2 mg/kg/day orally once daily (A II) for 21 days  TMP 15/mg/kg/day orally divided into 3 daily doses for 21 days  Adverse reactions include rash, anemia, thrombocytopenia, increased liver enzymes

62. July 2009 62 www.aidsetc.org Pneumocystis jiroveci (carinii): Treatment Adjunct Corticosteroids  Consider use in moderate to severe PCP  Use within 72 hours of diagnosis  Results in reduced respiratory failure, decreased ventilation requirements, and decreased mortality

63. July 2009 63 www.aidsetc.org Pneumocystis jiroveci (carinii): Treatment Adjunct (2) Corticosteroids  Dosing recommendations vary  Prednisone: 40 mg BID for 1-5 days; 40 mg once daily days 6-10; 20 mg once daily days 11-21  Alternative: prednisone 1 mg/kg BID days 1-5; 0.5 mg/kg BID days 6-10; 0.5 mg/kg once daily days 11-21

64. July 2009 64 www.aidsetc.org Pneumocystis jiroveci (carinii): Monitoring and Adverse Events  Short courses of corticosteroids have been used in some cases of PCP of moderate to severe intensity starting within 72 hours of diagnosis (A I)  As with other coinfection, IRIS may occur following initiation of ART but has been described infrequently in PCP  Most common adverse reaction to TMP-SMX includes rash and rarely erythema multiforme or Stevens- Johnson syndrome  Pentamidine is associated with renal toxicity, usually occurring 2 weeks after initiation of treatment

65. July 2009 65 www.aidsetc.org  This presentation was prepared by Arthur Ammann, MD, Clinical Professor of Pediatrics University of California and President of Global Strategies for HIV Prevention for the AETC National Resource Center, in July 2009  See the AETC NRC website for the most current version of this presentation: http://www.aidsetc.org About This Slide Set