HIV associated opportunistic infection

transcript

Susanne Burger, MD

Impact of HAART on the Incidence of Opportunistic Infections

CMV Retinitis

Toxoplasmosis

Typical Relationship of Clinical Manifestations to CD4 Count in HIV Infected Patients

LymphomaTuberculosis

Kaposi SarcomaHerpes Zoster

Criteria for Starting, Discontinuing, and Restarting Opportunistic Infection Prophylaxis for Adults with HIV

Criteria for Initiating Primary Prophylaxis

Criteria for Discontinuing Primary Prophylaxis

Criteria for Restarting Primary Prophylaxis

Criteria for Initiating Secondary Prophylaxis

Criteria for Discontinuing Secondary Prophylaxis

Criteria for Restarting Secondary Prophylaxis

PCP CD4 < 200 or oral candidasis

CD4 > 200for 3 mos

CD4 < 200 Prior PCP CD4 > 200 for 3 mos CD4 < 200

Toxoplasmosis + serum IgGCD4 < 100

CD4 > 200 for 3 mos

CD4 < 100 – 200

Prior toxoplasmic encephalitis

CD4 > 200 sustained and completed initial therapy and is asymptomatic

CD4 < 200

MAC CD4 < 50 CD4 > 100 for 3 mos

CD < 50 – 100 Documented disseminated disease

CD4 > 100 sustained and completed 12 mos of MAC tx and asymptomatic

CD4 < 100

Cryptococcosis none n/a n/a Documented disease

CD4 > 100 – 200 sustained and completed initial therapy and asymptomatic

CD4 < 100 - 200

Histoplasmosis none n/a n/a Documented disease

No criteria recommended for stopping

CMV none n/a n/a Documented end-organ disease

CD4 > 100 – 150 sustained and no evidence of active disease and regular exams

CD4 < 100 - 150

Approach to Respiratory Disease in HIV Infection: Diagnostic Clues

Parameter ExampleRapidity of onset > 3 days: PCP, Tb

< 3 days: bacteriaTemperature Afebrile: neoplasmCharacter of sputum Purulent: bacteria

Scant: PCP, Tb, virusLaboratory Tests WBC, LDH

↓O2 post exerciseX-ray atypical Pattern: Beware!

Isolation?

Pneumocystis Jiroveci(Formerly P. carinii)

• Taxonomy– Fungus vs. Protozoan

• Epidemology– Environmental source unknown

• Life Cycle– Unknown

• Transmission– Respiratory

• Well documented in rodents• Presumptive in man

Diagnosis of Pneumocystis Pneumonia

A 30 year-old male with HIV infection and fever, cough, and diffuse infiltrates has a bronchoscopy performed. Which of the following is the most sensitive and specific test to perform to establish whether or not pneumocystis is the causative pathogen?

a. PCR of the bronchalveolar lavage (BAL)b. Culture of the BALc. Immunoflourescent stain of the BALd. ELISA of the BALe. Serum PCR

A patient with HIV infection presents with PCP (room air pO2=82mHg). He has a history of a severe exfoliative rash to TMP-SMX.

Which of the following therapies would you recommend:

a. TMP-SMX + Prednisoneb.TMP + Dapsonec. Parenteral Pentamidined.Clindamycin plus pyremethaminee.Atovaquone

A 50 year-old male with HIV and PCP is receiving pentamidine 4mg/kg IV over 1 hr qd. On the ninth day of therapy, while awaiting transportation home, he has a syncopal episode.

What is this rhythm?

Toxicity Regarding Antipneumocystis Therapy

Drug IssuesTMP-SMX Toxicities: ↓WBC, ↓Plat, ↑LFT

↑Creat, ↑Amylase, rash, feverCross reactivity: dapsone (+/- 50%)

Pentamidine Hypotension, ↑Crea, ↑Amylase, ↓WBC↓Glucose: related to ↑Creaoccurs days-wks post-rxTorsade de Pointes

Atovaquone Absorption

Clindamycin + Primaquin Rash, LFT, diarrheaMethemoglobinemiaHemolytic anemia (G-6-PD)

Dapsone Rash, fever, ↑LFT, Hemolytic anemia (G-6-PD), peripheral neuropathy

22 y/o patient with CD4 = 69 and bilateral interstitial infiltrates on CXR has been started on treatment with iv bactrim for presumptive PCP. On day #3 he still c/o dyspnea and reports that his symptoms have not improved since admission to the hospital. What do you do?

Management of Patients with AIDS Related PCP Who are Failing TMP-SMP

• Add corticosteroids (if not already done)• Switch to alternative treatment • Reassess diagnosis

– Is PCP correct?– Are there any other pathogens?

• Is aggressive/longer term support appropriate?– Patient wishes – Realistic assessment of prognosis

A 34 y/o man who has been HIV pos for ~ 10 years is brought to the ER after a witnessed seizure. He had been receiving HAART until ~ 5 years ago when he dropped out of care. Family members report that he has had some memory loss and unusual behavior for the past 2 weeks. On PE is he is confused and disoriented.

Evaluation of CNS Mass Lesions in Patients with AIDS

ToxoplasmosisLymphomaPMLTuberculosisFungusNocardiaBacterialSyphilisKaposi SarcomaGlioblastoma

Radiologicnon specificextra CNS lesions

LaboratorySerology – Toxo IgG, crypt AgBlood culture – AFB, fungusCSF – Crypt Ag, CMV PCR, EBV PCRUrine – Histo Ag

Empiric Therapy

How is toxoplasmosis most often transmitted in the United States?

Clinical Manifestation of Toxoplasmosis when Acquired Post-Partum

Toxoplasmosis - Diagnosis

• Definite diagnosis: Biopsy with demonstration of tachyzoites

• Presumptive diagnosis acceptable when– CD4 < 200– Compatible neurologic disease– No prophylaxis– Serology: positive toxo IgG

Therapy for Cerebral Toxoplasmosis

• Preferred Regimen– Sulfadiazine + pyremethamine

• Alternative Regimen– Clindamycin + pyremethamine

• Less studied regimens– TMP-SMX– Atovaquone + sulfadiazine– Azithromycin + pyremethamine– Dapsone + pyremethamine

A 35 year-old male with HIV (CD4 = 30, VL 100k copies) not on HAART, is brought to the emergency room with several weeks of declining cognitive function, ataxia, and aphasia. CT scan shows multiple hypodense, non enhancing cerebral white matter lesions. The gray matter is spared. CSF analysis shows: WBC 25 (100% lymphs), protein 110 mg/dl; glucose 90 mg/dl; VDRL neg, Crypt Ag neg, PCR for JC virus positive

What therapy is effective for this condition:a. high dose acyclovirb. Cidofovirc. Vidarabined. Foscarnete. None of the above

Infectious Non-focal Brain Disease

Clinical Features

Lesion Type Temporal Progression

Level of Alertness Fever

PML Weeks Preserved Absent

AIDS dementia complex

Weeks/months Preserved Absent

CMV encephalitis Days/weeks Reduced Common

HIV associated CMV Disease

Pre-HAART, 30% of patients developed: – Retinitis– Colitis – Others:

• Pneumonitis• Ventriculoencephalitis• Myelitis • Radiculomyelopathy• Adrenalitis

Diagnosis of CMV Disease

• Serology (IgG, IgM)• Viremia common in asymptomatic persons with

low CD4• Histology required for diagnosis of colitis and

pneumonitis • ‘owl’s eye ‘ intranuclear inclusion bodies pathognomonic• Rare cells in the absence of clinical disease insignificant

• Retinitis clinical diagnoses• Fluffy exudate

• CNS – CMV PCR

CMV Detection in Specific Anatomic Sites

Site Significance

BAL None

Blood (cells, plasma) maybe

CSF Qualitative: probably

Mycobacterium Avium Intracellulare Complex

• Epidemiology: Ubiquitous in dirt, animals etc• Avium: 95% isolates• Transmission

– Respiratory and GI, environmental source undetermined– Person-to-person NOT likely

• Clinical manifestations– Fever, wasting, ↑nodes, ↑liver, ↑spleen– Rare as cause of lung disease– Labs: ↑alk pho, ↓Hb (severe), ↓albumin

Mycobacterium Avium Intracellulare: Diagnosis and Treatment

• Source of Isolates– Blood (if patient symptomatic)

Pos culture 80 – 90 %: Bactec (7-14 days), solid (21 days)– Sputum/Stool/Urine

• Low predictive value

• Treatment: Clarithro (or Azithro) + Ethambutol (+/- Rifabutin) x 1 year

Compatible clinical syndrome +

Isolation of M. avium

Show and Tell

Cryptococcal Meningitis in Patients with HIV Infection

• Epidemiology: CD4 count < 50 cells/mm3 (75% cases)• Diagnosis

– CSF: Ag positive 95-100%– Serum: CRAG positive 95-99%, – Blood Culture: positive 75%

• Poor prognosis– Abnormal mental status– Low CSF WBC

• Beware unusual presentations– Skin (molluscum)– Lung (variable x-ray)

– Screening with CRAG: Titer > 1:8 should be treated

Therapy of Cryptococcal Meningitis

Increased Intracranial Pressure (ICP)Association of Mortality with Baseline CSF Opening Pressure

Opening Pressure <190 – 249 mmn = 102

250 – 349 mmn = 59

> 350 mmn = 60

# (%) of Deaths 21 (21%) 16 (27%) 23 (38%)

Median mos. To death

10.5 7 6◊

◊ Pts with the highest baseline Ops (>250) also had higher titers CRAG and more frequent H/A, meningismus, papilledema, hearing loss and pathologic reflexes

Graybill et al. Clin Infect Dis. 2000;30:47

Management of increased ICP

• For pts with ICP > 250 mm H2O perform daily or qod LPs. Remove CSF volume up to 30 cc to reduce OP to 50% of the baseline OP.

• Placement of lumbar drain and option, but infections and drain malfunction are major concerns.

• Ventriculostomy catheter to drain and monitor ICP. High risk for infection.

• Ventriculoperitoneal (internalized) shunt in pts with or without evidence of hydrocephalus. Risks include potential infection, dissemination of cryptococcus, and shunt obstruction.

Serial Crypt Antigen Titers

• Serum– Changes do NOT correlate with therapeutic

response• CSF

– Changes are helpful but repeated LPs not necessary if patient is responding well clinically

• Note:– Some clinicians advocate LP with culture and Ag

before stopping maintenance: controversial

HIV associated opportunistic infection

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