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