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HIV associated opportunistic infection Susanne Burger, MD
HIV associated opportunistic infection
Susanne Burger, MD
Impact of HAART on the Incidence of Opportunistic Infections
PCP
MAC
CMV Retinitis
Toxoplasmosis
HAART
Typical Relationship of Clinical Manifestations to CD4 Count in HIV Infected Patients
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LymphomaTuberculosis
Kaposi SarcomaHerpes Zoster
Criteria for Starting, Discontinuing, and Restarting Opportunistic Infection Prophylaxis for Adults with HIV
OI
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
n/a
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.
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
