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AIDS and related syndrome

AIDS and related syndrome. Clinical manifestation and staging of HIV infection. Acute HIV infection or primary HIV infection Asymptomatic stage or clinical latency Early symptomatic stage or AIDS-related complex (ARC) Advanced HIV disease or AIDS. CD4 levels and common OIs.

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AIDS and related syndrome

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  1. AIDS and related syndrome

  2. Clinical manifestation and staging of HIV infection • Acute HIV infection or primary HIV infection • Asymptomatic stage or clinical latency • Early symptomatic stage or AIDS-related complex (ARC) • Advanced HIV disease or AIDS

  3. CD4 levels and common OIs

  4. CD4 levels and common OIs

  5. Natural Course of HIV Infection and Common Complications 1000 VL 900 CD4+ T cells Relative level of Plasma HIV-RNA 800 700 TB CD4+ cell Count 600 500 HZV Asymptomatic Acute HIV infection syndrome 400 OHL 300 200 OC PPE PCP 100 TB CM CMV, MAC 0 0 1 2 3 4 5 1 2 3 4 5 6 7 8 9 10 11 Months Years After HIV Infection

  6. Advanced HIV disease or AIDS • CD4+ T cell < 200 cells/mm3 • Common AIDS-defining illness in HIV – infected Thai adults • Candidiasis • Cryptococcosis • Penicillosis marneffei • Histoplasmosis • Cytomegalovirus • Mycobacterium avium complex • Toxoplasmosis

  7. Candidiasis • Candida infection in AIDS is almost exclusively mucosal • Oropharyngeal candidiasis occurs in 74% of HIV-infected patients • 1/3 is recurrent and more severe as immunodeficiency advances • Esophageal involvement is reported in 20 to 40% of all AIDS patients

  8. Clinical features of oral candidiasis • Most patients are symptomatic and may complain of some oral discomfort • 4 forms of oral lesions: pseudomembranous, erythematous (or atrophic), hypertrophic, and angular cheilitis

  9. Pseudomembranous (thrush) type Erythematous (atrophic) type Hypertrophic type

  10. Clinical features of vaginal candidiasis • Most patients present with vaginal itching, burning or pain and vaginal discharge • Examination of the vaginal cavity reveals thrush, identical to that seen in the oropharynx

  11. Clinical features of esophageal candidiasis • Typical symptom: dysphagia or odynophagia • Esophageal lesions: pseudomembranes, erosions, and ulcers • Combination of oral candidiasis and esophageal symptoms is both specific and sensitive in predicting esophageal involvement

  12. Clinical features of esophageal candidiasis • Patients who present in this manner can be treated empirically with antifungal therapy • Endoscopy is reserved in those patients who fail to respond or to evaluate for the presence of other diagnoses: HSV or CMV esophagitis, idiopathic ulceration

  13. Diagnosis of candidiasis • Fungal cultures are rarely required for diagnosis and can cause confusion, since many patients are colonized with Candida • Scraping of a lesion will show characteristic spherical budding yeasts and pseudohyphae (KOH preparation or gram stain)

  14. Diagnosis of candidiasis

  15. Therapeutic options for oral candidiasis

  16. Treatment of vulvovaginal candidiasis • Initial episodes are managed readily with topical therapy (clotrimazole, miconazole, or butoconazole) • Systemic therapy is rarely needed for uncomplicated cases • Fluconazole single dose of 150 mg orally is a popular alternative

  17. Candida esophagitis Treatment of acute infection • Drug(s) of first choice: Fluconazole 200 up to 400 mg/d x 2-3 wk • Alternatives:Ketoconazole 200-400 mg bid x2-3 wk or Itraconazole 100-200 mg bid or Amphotericin B 0.3-0.5 mg/kg/d IV +/- 5-FC 100 mg/kg/d x 5-7 days Suppressive therapy • Drug(s) of first choice: Fluconazole 100-200 mg/d • Alternatives:Ketoconazole 200 mg/d orItraconazole 200 mg/d or Nystatin or clotrimazole

  18. Cryptococcosis : Cryptococcal meningitis • Virtually all HIV-associated infection is caused by C. neoformans var. neoformans (serotypes A and D) • Most cases are seen in patients with CD4 <50 cells/mm3 • acute primary infection or reactivation of previously dormant disease

  19. Clinical features of cryptococcosis

  20. Diagnosis of cryptococcosis Wright’s stain Acid-fast stain

  21. Diagnosis of cryptococcosis • CSF: mildly elevated protein, normal or slightly low glucose, a few lymphocytes, and numerous organisms • Cryptococcal antigen is almost invariably detectable in the CSF at high titer • Opening pressure is elevated in up to 25%: important prognostic and therapeutic implications

  22. Diagnosis of cryptococcosis • CSF culture positive • India ink positive

  23. Diagnosis of cryptococcosis • Cryptococcal antigen in the serum is highly sensitive and specific for C. neoformans infection • Positive serum cryptococcal antigen titer >1:8 is regarded as presumptive evidence of cryptococcal infection and warrants antifungal therapy, even if infection is not subsequently documented

  24. Cryptococcal Meningitis Treatment of acute infection • Drug(s) of first choice: • Amphotericin B 0.7 mg/kg/d IV +/- flucytosine 100 mg/kg/d x 10-14 days • then fluconazole 400 mg bid x 2 days, then 400 mg/d x 8-10 wk or itraconazole 400 mg/d x 8-10 wk • Alternatives: • Fluconazole 400 mg/d x 6-10 wk • Itraconazole 200 mg tid x 3 days, then 200 mg bid x 6-10 wk • Fluconazole 400 mg/d plus flucytosine 100 mg/kg/d x 6-10 wk

  25. Cryptococcal Meningitis Suppressive therapy • Drug of first choice: Fluconazole 200 mg up to 400 mg/day • Alternatives: • Amphotericin B 0.6-1 mg/kg 1-3x/wk • Itraconazole 400 mg/d or 200 mg oral suspension/d Prophylaxis (CD4 <50) • Drug of first choice: Fluconazole 200 mg/d • Alternative:Itraconazole 200 mg/d or 100 mg oral suspension/d

  26. การป้องกัน cryptococcosis ในประเทศไทย • ข้อบ่งชี้ • CD4 <100/mm3 • เคยเป็น cryptococcosis มาก่อน • ยาที่ใช้ Fluconazole 400 mg weekly • ผู้ป่วยที่ได้ยาต้านไวรัสและมี CD4 > 100-200/mm3 อย่างน้อย 6 เดือน สามารถหยุดยาป้องกันได้

  27. Penicilliosis marneffei • CD4 +T cell < 100 cells/mm3 • Penicillium marneffei, a dimorphic fungus • Endemic in Southeast Asia (especially Northern Thailand and Southern China) • Potential cause of infection in patients in endemic areas or with a history of travel to endemic areas

  28. Clinical features of 74 hiv-infected patients with disseminated P. marneffei infection Source: Sirisanthana T, et al. Clin Infect Dis. 1998;26:1107-10

  29. Penicilliosismarneffei

  30. Penicilliosis marneffei

  31. Diagnosis of penicilliosis marneffei • Wright stain : smear from skin lesion, node biopsy, marrow biopsy : 2*3-6 um yeast • Culture from skin, bone marrow,LN • Hemoculture

  32. Diagnosis of penicilliosis marneffei

  33. Penicilliosis marneffei Treatment of acute infection • Drug(s) of first choice: • Amphotericin B 0.7-1.0 mg/kg/d IV or Itraconazole 400 mg/d for 10-12 wk • Amphotericin B 0.7-1.0 mg/kg/d IV x 2 wk then Itraconazole 400 mg/d for 10 wk • Alternative:Itraconazole, Ketoconazole or fluconazole Suppressive therapy • Drug(s) of first choice: Itraconazole 200 mg/d

  34. Histoplasmosis • Histoplasma capsulatum, a dimorphic fungus • Endemic in the Mississippi and Ohio river valleys of North America, certain areas of Central and South America, and the Caribbean • Mycelial form is found in the soil; particularly soil associated with bird roosts, and caves

  35. Clinical features of histoplasmosis • most common: fever and weight loss, ~ 75% of patients • Respiratory complaints, abdominal pain or gastrointestinal bleeding • 5-10% have an acute septic shock-like syndrome, very poor prognosis • Skin lesions: uncommon, molluscum contagiosum-like

  36. Histoplasmosis

  37. Disseminated histoplasmosis Treatment of acute infection • Drug(s) of first choice: • Amphotericin B 0.7-1.0 mg/kg/d IV > 7-14 days • Itraconazole 300 mg bid x 3 days then 200 mg bid x 10-12 wk • Alternative:Fluconazole 400 mg/d Suppressive therapy • Drug(s) of first choice: Itraconazole 200-400 mg/d • Alternatives: Amphotericin B 1.0 mg/kg q 1-2x /wk or Fluconazole 400 mg/d

  38. การป้องกัน penicilliosis และ Histoplasmosis ในประเทศไทย • ข้อบ่งชี้ • CD4 <100/mm3 (เฉพาะภาคเหนือ) • เคยเป็น penicilliosis มาก่อน • ยาที่ใช้ Itraconazole 200 mg qd • ผู้ป่วยที่ได้ยาต้านไวรัสและมี CD4 > 100-200/mm3 อย่างน้อย 6 เดือน สามารถหยุดยาป้องกันได้

  39. Toxoplasmosis • Toxoplasma gondii • CD4T cell < 100 cells/mm3 • Reactivation of infection • Organ involvement • Brain is the most common site • Lungs • Eye: chorioretinitis • GI • Muscle

  40. Transmission • Ingestion of raw or undercooked meat that contains cysts • Ingestion of water or food contaminated with oocysts • Transplacental transmission

  41. Toxoplamosis Encephalitis (TE) • Cerebritis or brain abscess • Diffuse form less common • Clinical • Headache • Neurological deficits • Seizure • Alteration of consciousness • Meningismus • Movement disorders • Neuropsychiatric

  42. Diagnosis of toxoplasmosis • Clinical • CT brain scan or MRI • Toxoplasma titer • Response to treatment • Brain biopsy

  43. Toxoplasmosis • Multiple brain lesions • Brain edema • Basal ganglia • Ring enhancement

  44. CSF findings in TE • nonspecific • mild mononuclear pleocytosis and • mild to moderate elevations in CSF protein

  45. Toxoplasmosis Treatment • First choice Pyrimethamine 200 mg x 1 then 75-100 mg /d + Sulfadiazine 1-1.5 g q 6 hr + Leukoverin 15 mg qd (if available) for 4-6 wks • Alternative Pyrimethamine + Leukoverin + Clindamycin 600 mg q 6 hr

  46. Primary Prophylaxis ofToxoplasmosis Indications 1. CD4 cell count < 100/mm3 2. Ig G Ab to Toxoplasma +ve(IDSA)

  47. Regimens for Primary Prophylaxis First choice • TMP-SMX 1 DS qd (AII) Alternative • TMP-SMX 1 SS qd (BIII) • Dapsone 50 mg qd + Pyrimethamine 50 mg qw + Leukoverin 25 mg qw (if available) (BI) • Dapsone 200 mg qw+ Pyrimethamine 75 mg qw + Leukoverin 25 mg qw (if available) (BI)

  48. Regimens for Secondary Prophylaxis First choice • Sulfadiazine 500-1000mg qid + • Pyrimethamine 25-50 mg/d + • Leucoverin 10-25mg/d (AI) Alternative • Clindamycin 300-450mg q 6-8 hr + • Pyrimethamine 25-50 mg/d + • Leucoverin 10-25mg/d (BI)

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