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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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
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
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
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
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
Pseudomembranous (thrush) type Erythematous (atrophic) type Hypertrophic type
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
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
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
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)
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
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
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
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
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
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
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
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
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
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
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
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
Toxoplasmosis • Toxoplasma gondii • CD4T cell < 100 cells/mm3 • Reactivation of infection • Organ involvement • Brain is the most common site • Lungs • Eye: chorioretinitis • GI • Muscle
Transmission • Ingestion of raw or undercooked meat that contains cysts • Ingestion of water or food contaminated with oocysts • Transplacental transmission
Toxoplamosis Encephalitis (TE) • Cerebritis or brain abscess • Diffuse form less common • Clinical • Headache • Neurological deficits • Seizure • Alteration of consciousness • Meningismus • Movement disorders • Neuropsychiatric
Diagnosis of toxoplasmosis • Clinical • CT brain scan or MRI • Toxoplasma titer • Response to treatment • Brain biopsy
