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Common Opportunistic Infections in HIV Patients
Chris Farnitano, MD
Monday, August 31, 2009
Noon Conference
Objectives
• Discuss most common opportunistic infections (OIs): Dx and Rx
• Discuss immune reconstitution disease
• Review primary OI prophylaxis
Forms
What are the most common OI’s?
• Cohort Studies in pre-triple therapy era:– Candida– Pneumocystis Carinii– Cytomegalovirus– Mycobacterium Avium Complex– Pneumocystis - second episode– Toxoplasmi gondii– Herpes zoster
Causes of death, PHC HIV clinic
• 2007-9– RH: Crypto meningitis
– TW: street drug overdose
– SA: sepsis, pneumonia and massive hemoptysis
– DW: metastatic prostate ca
– RP: CVA, laryngeal ca
– VA: PML (progressive multifocal leukencephalopathy)
– AM: bacterial pneumonia, ETOH cirrhosis, wasting
OIs diagnosed, PHC HIV clinic
• 2005-9– PCP pneumonia– Esophageal Candidiasis– Herpes Simplex– Herpes Zoster– M. Kansasii immune reconstitution pneumonia– Mycobacterium Avium Complex (MAC)– Cryptococcal Fungemia, meningitis– Histoplasmosis – PML
Effect of HAART on Opportunistic Infection Incidence• Most OI’s have declined 80-90%
• OI’s seen now mostly in 3 groups– undiagnosed HIV+– not in care or not adhering to therapy– long time “battle-scarred warriors” failing after
a long history of multiple regimens
More people living with AIDS
Pyramid or iceberg model
Strata of Pyramid
• >350 T Cells
• 350-200
• 50-200
• <50
>350 T Cells
• Increased incidence of diseases that also affect normal hosts:– Recurrent Vaginal Candidiasis– Pulmonary Tuberculosis– Pnuemococcal Pneumonia– Cervical Dysplasia
Pulmonary TB
200-350 T Cells:
• Herpes Simplex
• Herpes Zoster
• Thrush
Herpes Zoster (Shingles)
50-200 T Cells:
• Pneumocystis Carinii Pnuemonia
• Toxoplasmosis
• Cryptococcus
Toxoplasmosis
<50 T Cells
• CMV Retinitis
• Mycobacterium Avium Complex
• Cryptosporidiosis
• Progressive Multifocal Leukencephalopathy
PML
Ockham's razor does not apply for advanced AIDS
• -often multiple diagnoses present simultaneously– ie PCP, CMV, KS, Cocci– 12% of bacterial pneumonias also have PCP– 10% of PCP pneumonia complicated by
bacterial infection– search for second etiology if patient not
improving
Immune reconstitution diseases(HAART attacks)
• MAC adenitis
• CMV
• TB
• PCP
Primary OI prophylaxis
• PCP -T cells <200 or thrush
• Toxo -T cells <100 and +Toxo titer
• MAC - Tcells <50
• TB – INH x 9 months if PPD >5mm or quantiferon-TB positive
Quantiferon vs. TST in HIV patients• Quantiferon not approved for use in immunocomprimised• 147 HIV patients in New Orleans given both tests:
– 36% did not return for TST reading– 15 positive by quantiferon– 1 positive by TST– Quantiferon is more sensitive but without a gold standard for
latent TB infection cannot say whether it is more or less specific
• Another study showed similar positive test result rates but a better correlation with risk factors for quantiferon vs. TST suggesting quantiferon is a more specific test
Quantiferon vs. TST in HIV patients
• “Given the high risk for progression to active disease in HIV-infected persons, any HIV-infected person with reactivity on any of the current LTBI diagnostic tests should be considered infected with M. tuberculosis”
• ----CDC guidelines, 3/24/09
PCP Prophylaxis
• Septra SS or DS qd or DS TIW– Single strength has similar efficacy with fewer adverse
reactions (I.e. late onset rash, hepatotoxicity, fever)– 25-50% of AIDS pts. D/c Septra DS due to reactions
• Septra Desensitization:– 1cc qd x 3d, then 2cc qd x 3d, then 5ccqd x 3d, then one SS
tab qd
• Dapsone 100mg qd +pyramethamine 50mg qweek + leukovorin 25mg qweek
• Aerosolized pentamadine 300mg q month• Atavaquone 1500mg qd
Aerosolized pentamidine booth
Toxo prophylaxis
• Septra SS or DS qd or DS TIW
• Septra Desensitisation:– 1cc qd x 3d, then 2cc qd x 3d, then 5ccqd x 3d,
then one SS tab qd
• Dapsone 100mg qd +pyramethamine 50mg qweek + leukovorin 25mg qweek
• Atovaquone 1500mg qd
MAC prophylaxis
• Zithromax 600mg x 2 tabs qweek reduces infection rate 59%
• Also seems to reduce risk of PCP
Specific Opportunistic Infections
Case Study: HW
• 51 yo male with poor adherence to meds
• HIV + since at least 1996
• 1st episode thrush March,2005– C/o dry mouth– Exam: white patches on buccal mucosa– T Cells 54– Treated with fluconazole, sx resolve
Case Study: HW
• Recurrent thrush July, 2005– Fluconazole again prescribed
• September, 2005– C/o odynophagia– Dx: probably esophageal candidiasis– Fluconazole again prescribed– Sx resolve in 3 days
Case Study: HW
• Recurrent odynophagia January, 2006– Switched to itraconazole liquid– 3 weeks later:
• odynophagia resolved• Thrush persists, resolved on re-exam March, 2006
• August, 2006-March, 2007– Recurrent episodes of thrush and esophageal
candidiasis due to non-adherence to intraconazole– Each episode improves when patient is adherent
Case Study: HW
• April, 2007– Persistent thrush despite stated adherence– Switched to Voriconazole– Sx resolveNovember, 2007 T Cells 5 Weight 121# (baseline 198#)-recurrent odynophagia despite adherence to voriconazoleAdmitted for IV CapsofunginSx markedly improve in 24 hoursFungal Cx: Candida AlbicansSensitivities: resistant to fluconazole, itraconazole and
voriconazole
Case Study: HW
• December 2007-August 2008– Persistent extensive thrush – Continued on Voriconazole– T cells 54 -> 12
August 2008: moves in with sisters after hospital stay, adherence improves markedly
January 2009: T cells 77, thrush much improved
April, 2009: T cells 239, thrush resolved
Candida
• Thrush
• Angular Chelitis
• Vaginal Candidiasis
• Esophageal Candidiasis
Thrush
• cottage cheese plaques
• soft palate, buccal mucosa, tonsils
• can be removed with a tongue blade
• also erythematous form without exudate
Thrush
Angular chelitis
• pain
• fissures
• erythema
• difficulty opening mouth
Angular Chelitis
Recurrent Vaginal Candidiasis
• less frequent than you would expect, unless T Cells<100
• can use Fluconazole 200mg qweek for suppression
Esophageal Candidiasis
• odynophagia• usually also has thrush (positive predictive value
is 90%, but 18% of esophageal candidiasis presents without thrush)
• Treat empirically x 5-7 days• if not better, scope to r/o other causes:
– CMV, HSV, idopathic esophageal ulcers, lymphoma
• Secondary prophylaxis needed
Esophageal Candidiasis
Treatment:
• Fluconazole 100-200mg qd until sx resolve
• Alternatives for resistant Candida:– Higher dose fluconazole (400-800 mg/d– Itraconazole– Voriconazole– IV Capsofungin– IV Amphotericin
PCP - Who gets it:
• Septra prophylaxis highly efficatious
• Risk if T Cells <200 or thrush
PCP - Symptoms
• insidious onset– 2-4 weeks of progressive symptoms
• Fever, sweats, weight loss, fatigue, nonproductive cough
• progressive dyspnea
• retrosternal discomfort
PCP - Signs
• Lung exam usually normal
• CXR: bilateral diffuse interstitial infiltrate in 80-90%
• LDH>400 in 62%
• PO2<75 in 66%
PCP Pneumonia
Severe PCP
•
PCP - Diagnosis
• Induced sputum x 3 in early AM (all on same day): 50-70% sensitive
• Bronchoscopy (+/-Bx): 80-90% sensitive
• PCR based tests
• To collect sputums or go directly to bronch?
PCP - Treatment
• Can begin before Dx confirmed without affecting diagnostic yield
• Prednisone 40mg BID x 5d. Then taper over total 21d.
• Septra 15mgTMP/kg/d IV div. Q8h x 21d. – Switch to po when improved
• give first dose prednisone 15-30 minutes before Septra
Approach to HIV patient with Pneumonia
• What is the T Cell Count?
T cell Count >200:• TB presents in typical fashion
– cavitary in 50-60%– isolate only if CXR suspicious for TB
• Opportunistic infections unlikely– can treat empirically for bacterial infection– S. pneumoniae, H. Flu most common
(encapsulated)
• Also consider: Non-Hodgkin’s Lymphoma
T cell Count <200:
• TB presents as lower lobe disease, adenopathy, miliary or interstitial pattern– cavitary in only 29%– isolate all abnormal CXR until TB ruled out
• Opportunistic infections likely– obtain definitive diagnosis whenever possible– Coccidiomycosis, Cryptococcus, Aspergillis– CMV, KS, M.TB, M. Kansasii
Don’t Treat PCP empirically
• experienced physicians make wrong clinical diagnosis in 20% of suspected PCP
• patients treated empirically have higher risk of death than patients who underwent bronch
• High incidence of rash toward end of 21 d. Septra course
• Adjunctive steroids may exacerbate other OIs• Many etiologies left uncovered
Cytomegalovirus Retinitis - Who Gets It?
• Rare above 50 T Cells
• Reactivation disease: most HIV patients CMV IgG+ (90% of gay HIV+ men)
• 90% of CMV disease is retinitis
Cytomegalovirus Retinitis - Symptoms
• painless, progressive visual loss
• unilateral blurry vision
• floaters
Cytomegalovirus Retinitis - Signs
• coalescing white perivascular exudates
• surrounded by hemorrhage
• brushfire pattern or tomato and cheese pizza
Cytomegalovirus Retinitis
Cytomegalovirus Retinitis
Cytomegalovirus Retinitis - Diagnosis
• if you suspect it, obtain ophthalmologist confirmation within 24-48 hrs.
Cytomegalovirus Retinitis - Treatment
• Valgancyclovir 900mg PO BID x 21 days, then qd
• Adverse effects: – neutropenia ANC<500 in 15%– thrombocytopenia– anemia– 50%: nausea, vomiting, abdominal pain or
diarrhea
Gangcyclivir intraocular implant
• Consider in addition to systemic therapy:– Surgically implanted depo device– Effective for 6 months– Replace at 6 months if still not immune
reconstituted– Consider for sight threatening lesions near the
central visual field
Mycobacterium avium Complex - Who gets it?
• T Cells <50
• screen with blood culture for AFB x 1 q 3 months to detect subclinical disease
Mycobacterium avium Complex - Symptoms
• fever, night sweats
• weight loss
• diarrhea
Mycobacterium avium Complex - Signs
• anemia
• neutropenia
Mycobacterium avium Complex - Diagnosis
• Blood culture usually positive if symptomatic but takes weeks to grow
• If need to know sooner then do bone marrow Bx
• Positive sputum culture usually colonization, not active disease
• Positive stool culture may be colonization, not active disease
MAC-filled macrophages in spleen
Mycobacterium avium Complex - Treatment
• Clarithromycin 500mg BID +
• Ethambutol 15mg/kg/d +/-
• Rifabutin 300mg qd
• Treatment failure rate is high without immune reconstitution– drug toxicity– development of resistance
Forms
Summary:
• Pyramid approach
• Prophylaxis simple: Septra and Zithromax
• Rule out TB in pneumonia with T Cells <200
• Avoid treating PCP empirically
• An ounce of prevention pills is worth a pound of Treatment pills
An ounce of prevention pills is worth a pound of Treatment pills
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