Common Opportunistic Infections in HIV Patients Chris Farnitano, MD Monday, August 31, 2009 Noon...
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Transcript of Common Opportunistic Infections in HIV Patients Chris Farnitano, MD Monday, August 31, 2009 Noon...
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