HIV in the ICUHIV in the ICU

Jason Halperin, MS IVJason Halperin, MS IV

May 14, 2009May 14, 2009

History & PhysicalHistory & PhysicalHPI: 60 y/o man with 23 year history of HPI: 60 y/o man with 23 year history of HIV, HCV, COPD, CKD stage II, HIV, HCV, COPD, CKD stage II, transferred from Bridgton Hospital for transferred from Bridgton Hospital for sepsis and respiratory failure secondary to sepsis and respiratory failure secondary to multilobar pneumonia. multilobar pneumonia.

He presented with 3 days of productive He presented with 3 days of productive cough, SOB, chills, night sweats and cough, SOB, chills, night sweats and fever. Per Patient’s Partner - no fever. Per Patient’s Partner - no hemoptysis, nausea, vomiting, diarrhea or hemoptysis, nausea, vomiting, diarrhea or rash. No recent travel or sick contacts. rash. No recent travel or sick contacts.

History & PhysicalHistory & Physical

HPI Cont: He was afebrile at presentation, sats in HPI Cont: He was afebrile at presentation, sats in low 80s, and was intubated for worsening respiratory low 80s, and was intubated for worsening respiratory acidosis. His blood pressures began to decrease, acidosis. His blood pressures began to decrease, norepinephrine was started and patient was life-norepinephrine was started and patient was life-flighted to MMC. flighted to MMC.

On arrival, patient continued to be in septic shock, On arrival, patient continued to be in septic shock, vasopressin was added to his Norepinephrine. Cont. vasopressin was added to his Norepinephrine. Cont. on Vancomycin & Ceftriaxone. on Vancomycin & Ceftriaxone.

Past Medical HistoryPast Medical History

HIV>20 year HIV>20 year CD 4 count in December, 2008 CD 4 count in December, 2008 of 236 with undetectable HIV viral loadof 236 with undetectable HIV viral load

HypertensionHypertensionCOPDCOPDHepatitis C Hepatitis C undetectable viral load in undetectable viral load inDecemberDecemberHyperlipidemiaHyperlipidemia

Meds/AllergiesMeds/Allergies

Medications:Medications:Toprol XL 100mg q dailyToprol XL 100mg q dailyZoloft 100mg q dailyZoloft 100mg q dailyEfavirenz 600mg q dailyEfavirenz 600mg q dailyTenofovir 300mg q dailyTenofovir 300mg q dailyLamuvidine 300mg q dailyLamuvidine 300mg q daily

Allergies: NKDAAllergies: NKDA

Social HistorySocial History

Patient in relationship with life partner, Patient in relationship with life partner, lived a “wild life” until settling down 15 lived a “wild life” until settling down 15 years ago including heavy drinking, IV years ago including heavy drinking, IV drug use and with 40 pack year smoking drug use and with 40 pack year smoking history quit 15 years ago.history quit 15 years ago.

Works at Christmas Tree Shops as Works at Christmas Tree Shops as manager, artist, no children, owns a dog, manager, artist, no children, owns a dog, no cats. no cats.

Physical ExamPhysical Exam

Vitals: Temperature 36.4 degrees Celsius, pulse 112, blood pressure 110/58, respirations 16. On CMV 40% Vt – 700, ARDSnet Protocol

General: the patient is sedated and slightly diaphoretic. He does not respond to verbal commands or sternal rub with minimal sedation.

HEENT: Pupils are slow to react. No scleral icterus or conjunctival hemorrhage is appreciated. He is intubated, no jugular venous distention.

Cardiovascular: Regular rate and rhythm; tachycardic; normal S1 and S2.

Pulmonary: Coarse breath sounds bilaterally; he is ventilated.

Abdomen: Bowel sounds present, soft and nondistended, no organomegaly appreciated.

Extremities: 2+ bilateral lower extremity edema; Venodynes are in situ. There is appreciable onychomycosis in the big toes bilaterally. No splinter hemmorhages, janeway lesions or other stigmata of endocarditis

Ancillary Lab DataAncillary Lab Data

Abnormal: WBC – 1.2, ANC 1060, Bands Abnormal: WBC – 1.2, ANC 1060, Bands 13, Hgb – 11.1, Hct – 34.8, Plts – 89, BUN 13, Hgb – 11.1, Hct – 34.8, Plts – 89, BUN – 89, Cr – 3.14, Ast - 85– 89, Cr – 3.14, Ast - 85

Normal: Na – 133, K – 5.2, Cl – 106, Normal: Na – 133, K – 5.2, Cl – 106, Glucose – 87, Alt - 36Glucose – 87, Alt - 36

CD4 Cell Count Ranges for Selected HIV-Related CD4 Cell Count Ranges for Selected HIV-Related

and Non-HIV-Related Respiratory Illnessesand Non-HIV-Related Respiratory Illnesses Any CD4 cell countAny CD4 cell countUpper respiratory tract infection Upper respiratory tract infection Pharyngitis Pharyngitis Acute bronchitis Acute bronchitis Obstructive airway disease Obstructive airway disease Bacterial pneumonia Bacterial pneumonia Tuberculosis Tuberculosis Non-Hodgkin lymphoma Non-Hodgkin lymphoma Pulmonary embolus Pulmonary embolus Bronchogenic carcinoma Bronchogenic carcinoma

CD4 Count ≤500 Cells/µLCD4 Count ≤500 Cells/µLBacterial pneumonia (recurrent) Bacterial pneumonia (recurrent) Pulmonary mycobacterial pneumoniaPulmonary mycobacterial pneumonia

CD4 Count ≤200 Cells/µLCD4 Count ≤200 Cells/µLPneumocystis pneumonia Pneumocystis pneumonia Cryptococcus neoformans Cryptococcus neoformans pneumonia/pneumonitis pneumonia/pneumonitis Bacterial pneumonia (associated with Bacterial pneumonia (associated with bacteremia/sepsis) bacteremia/sepsis) Disseminated or extrapulmonary Disseminated or extrapulmonary tuberculosistuberculosis

CD4 Count ≤100 Cells/µLCD4 Count ≤100 Cells/µL Pulmonary Kaposi sarcoma Pulmonary Kaposi sarcoma Bacterial pneumonia (gram-negative Bacterial pneumonia (gram-negative

bacilli and bacilli and Staphylococcus aureusStaphylococcus aureus increased) increased)

ToxoplasmaToxoplasma pneumonitis pneumonitis

CD4 Count ≤50 Cells/µLCD4 Count ≤50 Cells/µLDisseminated Disseminated Histoplasma capsulatumHistoplasma capsulatumCytomegalovirus pneumonitis Cytomegalovirus pneumonitis Disseminated Disseminated Mycobacterium aviumMycobacterium avium complex complex AspergillusAspergillus spp pneumonia spp pneumonia

Pneumonia in the era of HAARTPneumonia in the era of HAART

Viale, Pierluigi et al. Pneumonia in the ICU Viale, Pierluigi et al. Pneumonia in the ICU AIDS AIDS 20042004

113 cases, 29 (25.6%) were PCP, 76 (67.2%) were 113 cases, 29 (25.6%) were PCP, 76 (67.2%) were bacterial CAP and 6 (5.6%) were caused by bacterial CAP and 6 (5.6%) were caused by Mycobacterium tuberculosisMycobacterium tuberculosis and two (1.8%) were and two (1.8%) were caused by MOTT. caused by MOTT.

With regard to bacterial CAP, With regard to bacterial CAP, Streptococcus Streptococcus pneumoniaepneumoniae was the more frequent etiological agent was the more frequent etiological agent (34 cases), followed by (34 cases), followed by Staphylococcus aureusStaphylococcus aureus (12 (12 cases), cases), Pseudomonas aeruginosaPseudomonas aeruginosa (9 cases), (9 cases), Haemophilus influenzaeHaemophilus influenzae (6 cases). (6 cases).

Signs and Symptoms of Common Signs and Symptoms of Common HIV-Associated Pulmonary Infections HIV-Associated Pulmonary Infections

Fei et al. Fei et al. HIV Associated Pneumonias AIDS (2006)HIV Associated Pneumonias AIDS (2006) BacterialBacterial

PneumoniaPneumonia

PCPPCP TuberculosisTuberculosis

OrganismOrganism Streptococcus pneumoniae,Haemophilus species,Pseudomonas aeruginosa, etc.

Pneumocystis jirovecii

Mycobacterium tuberculosis

Signs and Signs and SymptomsSymptoms

Cough with

Purulent sputum,

Fever, Chills Acute

Onset: symptoms <1 week

Nonproductive cough, shortness of breath, feverGradual onset,symptoms >2 weeks

Cough, fever, night sweats, weight loss, swollenlymph nodesGradual onset, symptoms >2 weeks

Steptococcal PneumoniaSteptococcal Pneumonia

Blood cultures positive for Blood cultures positive for gram positive cocci in pairs gram positive cocci in pairs sensitive to ceftriaxone.sensitive to ceftriaxone.

Patient was continued on Patient was continued on ceftriaxone and vancomycin ceftriaxone and vancomycin was discontinued.was discontinued.

Would You Continue His ARVs?Would You Continue His ARVs?

Can antiretroviral therapy improve the outcome among critically ill patients?

Do the risks associated with these medications outweigh the possible benefits, specifically in terms of drug interaction vs the development of resistance?

Should patients who are already receiving antiretroviral therapy continue to receive treatment in the ICU?

PCP Study & SF Gen PolicyPCP Study & SF Gen Policy

Morris et al. Morris et al. Intensive care of HIV-infected patients Intensive care of HIV-infected patients during the era of HAARTduring the era of HAART, CHEST 2003 showed , CHEST 2003 showed starting, continuing or re-initiating HAART for PCP starting, continuing or re-initiating HAART for PCP decreased mortality rate from 63% to 25%, P=0.03decreased mortality rate from 63% to 25%, P=0.03

Huang et al. Huang et al. Intensive Care of Patients with HIV Intensive Care of Patients with HIV InfectionInfection NEJM 2006 NEJM 2006SF General Hospital policy states ARV should be SF General Hospital policy states ARV should be started/continued when CD4 cell counts are below started/continued when CD4 cell counts are below 200 due to risk of opportunistic infection. Otherwise 200 due to risk of opportunistic infection. Otherwise they recommended continue ARVs unless specific they recommended continue ARVs unless specific contraindications. contraindications.

BronchoscopyBronchoscopy

A bronchoscopy was A bronchoscopy was performed. There was a performed. There was a vascular endobronchial vascular endobronchial lesion at the right lesion at the right secondary carina secondary carina obstructing the RUL with a obstructing the RUL with a friable appearance, friable appearance, suggesting a Kaposi's suggesting a Kaposi's Sarcoma. Sarcoma.

Diagnosis? Plts 38,000Diagnosis? Plts 38,000

Too vascular, PCR HHV 8Too vascular, PCR HHV 8

Kaposi SarcomaKaposi Sarcoma

KS occurs in 6 to 20 percent of HIV-infected KS occurs in 6 to 20 percent of HIV-infected homosexual or bisexual men. homosexual or bisexual men.

HHV 8 causes malignant transformation by HHV 8 causes malignant transformation by mechanism similar to HPV, inactivation of the mechanism similar to HPV, inactivation of the RB tumor suppressor gene.RB tumor suppressor gene.

Most commonly sexually transmitted, but it Most commonly sexually transmitted, but it has been seen with kidney transplantation.has been seen with kidney transplantation.

Unclear why KS seen in homosexual/bisexual Unclear why KS seen in homosexual/bisexual menmen

Treatment of Pulmonary Treatment of Pulmonary Kaposi SarcomaKaposi Sarcoma

Initiate HAART, if patient is not currently Initiate HAART, if patient is not currently being treated. Cutaneous KS HAARTbeing treated. Cutaneous KS HAART

Chemotherapy is recommended with Chemotherapy is recommended with pulmonary Kaposi Sarcoma - The two pulmonary Kaposi Sarcoma - The two liposomal anthracyclines, pegylated liposomal anthracyclines, pegylated liposomal doxorubicin (Doxil), and liposomal doxorubicin (Doxil), and liposomal daunorubicin (DaunoXome), liposomal daunorubicin (DaunoXome), have become the first-line treatment for have become the first-line treatment for Pulmonary KS. Pulmonary KS.

Moritz Cohen Moritz Cohen Kaposi KaposiKaposvar, Hungary at Night Kaposvar, Hungary at Night

Diagnosis of AIDSDiagnosis of AIDS

Patient’s CD4 count returned at 22, Patient’s CD4 count returned at 22, demonstrating our patient had AIDS with demonstrating our patient had AIDS with an HIV viral load of 11,000an HIV viral load of 11,000

HAART was restarted with Efavirenz HAART was restarted with Efavirenz 600mg Daily, Tenofovir 300mg every 48 600mg Daily, Tenofovir 300mg every 48 hrs, and Lamuvidine 300mg every 48 hrs, and Lamuvidine 300mg every 48 hours. Due to his AKIhours. Due to his AKI

CD4 Cell Count Ranges for Selected HIV-Related CD4 Cell Count Ranges for Selected HIV-Related

and Non-HIV-Related Respiratory Illnessesand Non-HIV-Related Respiratory Illnesses Any CD4 cell countAny CD4 cell countUpper respiratory tract infection Upper respiratory tract infection Pharyngitis Pharyngitis Acute bronchitis Acute bronchitis Obstructive airway disease Obstructive airway disease Bacterial pneumonia Bacterial pneumonia Tuberculosis Tuberculosis Non-Hodgkin lymphoma Non-Hodgkin lymphoma Pulmonary embolus Pulmonary embolus Bronchogenic carcinoma Bronchogenic carcinoma

CD4 Count ≤500 Cells/µLCD4 Count ≤500 Cells/µLBacterial pneumonia (recurrent) Bacterial pneumonia (recurrent) Pulmonary mycobacterial pneumoniaPulmonary mycobacterial pneumonia

CD4 Count ≤200 Cells/µLCD4 Count ≤200 Cells/µLPneumocystis pneumonia Pneumocystis pneumonia Cryptococcus neoformans Cryptococcus neoformans pneumonia/pneumonitis pneumonia/pneumonitis Bacterial pneumonia (associated with Bacterial pneumonia (associated with bacteremia/sepsis) bacteremia/sepsis) Disseminated or extrapulmonary Disseminated or extrapulmonary tuberculosistuberculosis

CD4 Count ≤100 Cells/µLCD4 Count ≤100 Cells/µL Pulmonary Kaposi sarcoma Pulmonary Kaposi sarcoma Bacterial pneumonia (gram-negative Bacterial pneumonia (gram-negative

bacilli and bacilli and Staphylococcus aureusStaphylococcus aureus increased) increased)

ToxoplasmaToxoplasma pneumonitis pneumonitis

CD4 Count ≤50 Cells/µLCD4 Count ≤50 Cells/µLDisseminated Disseminated Histoplasma capsulatumHistoplasma capsulatumCytomegalovirus pneumonitis Cytomegalovirus pneumonitis Disseminated Disseminated Mycobacterium aviumMycobacterium avium complex complex AspergillusAspergillus spp pneumonia spp pneumonia

Disseminated Disseminated Histoplasma capsulatumHistoplasma capsulatum

Histoplasmosis is the most Histoplasmosis is the most prevalent endemic mycosis in prevalent endemic mycosis in the United States the United States Ohio Ohio River ValleyRiver ValleyPresent with overwhelming Present with overwhelming infection manifested by shock, infection manifested by shock, respiratory distress, hepatic respiratory distress, hepatic and renal failure, obtundation, and renal failure, obtundation, and coagulopathy.and coagulopathy.

High serum lactate High serum lactate dehydrogenase (LDH). dehydrogenase (LDH). Corcoran et al. Clin Infectious Corcoran et al. Clin Infectious DiseaseDisease 197 AIDS patients, avg. 1397 197 AIDS patients, avg. 1397

Histoplasma antigen detection in different body fluids in patients with AIDSHistoplasma antigen detection in different body fluids in patients with AIDS

Disseminated Disseminated Histoplasma capsulatumHistoplasma capsulatum

Histo Prophylaxis in AIDSHisto Prophylaxis in AIDS

The 2007 IDSA guidelines recommend The 2007 IDSA guidelines recommend prophylactic Itraconazole (200 mg/day) for prophylactic Itraconazole (200 mg/day) for patients with HIV who have a CD4 count below patients with HIV who have a CD4 count below 150/microL. 150/microL.

Who are at high risk because of occupational Who are at high risk because of occupational exposure to bird/bat droppings or who live in a exposure to bird/bat droppings or who live in a community with a hyperendemic rate (greater community with a hyperendemic rate (greater than 10 cases per 100 patients-years) of than 10 cases per 100 patients-years) of histoplasmosis. histoplasmosis.

Cytomegalovirus pneumonitisCytomegalovirus pneumonitis

CMV in AIDS: Saloman et CMV in AIDS: Saloman et al. (1998) reported 98 pts al. (1998) reported 98 pts with CMV pneumonitis all with CMV pneumonitis all respiratory symptoms respiratory symptoms (cough or dyspnea), (cough or dyspnea),

89% had fever, 83% had 89% had fever, 83% had radiological radiological abnormalities, and 56% abnormalities, and 56% had severe hypoxemia. had severe hypoxemia. Avg. CD4 count – 12Avg. CD4 count – 12

BAL culture is not a BAL culture is not a specific test for CMV specific test for CMV pneumonitis. pneumonitis.

High res chest CT usually demonstrates areas of ground glass opacity, again usually more pronounced at the periphery of both lungs.

Cytomegalovirus pneumonitisCytomegalovirus pneumonitis

Treatment of CMV is recommended in the Treatment of CMV is recommended in the presence of symptomatic pulmonary disease, presence of symptomatic pulmonary disease, evidence of CMV in the lung, and the absence of evidence of CMV in the lung, and the absence of other treatable pulmonary infections. other treatable pulmonary infections.

Gancyclovir 1Gancyclovir 1stst line. line.

High mortality best treatment HAART, Very High mortality best treatment HAART, Very difficult to diagnosedifficult to diagnose

Disseminated Disseminated Mycobacterium Mycobacterium AviumAvium Complex Complex

Clinical Presentation: Clinical Presentation: FeverFeverNight sweatsNight sweatsAbdominal pain,Abdominal pain,Diarrhea, Diarrhea, Weight loss (which often Weight loss (which often precedes the onset of precedes the onset of fever) fever)

Blood cultures most Blood cultures most sensitive for diagnosissensitive for diagnosis

Prophylaxis Prophylaxis Mycobacterium Mycobacterium AviumAvium Complex Complex

Prophylaxis:Prophylaxis:Azithromycin once weeklyAzithromycin once weeklyClarithromycin dailyClarithromycin daily

IDSA recommend: Discontinue MACIDSA recommend: Discontinue MACprophylaxis in patients whose CD4 countsprophylaxis in patients whose CD4 countsrise to above 100/microL for 3 continousrise to above 100/microL for 3 continousmonthsmonths

MAC TreatmentMAC Treatment

The Public Health Service The Public Health Service Task Force recommends Task Force recommends that MAC treatment that MAC treatment includes:includes: clarithromycin (Biaxin; 500mg clarithromycin (Biaxin; 500mg twice a day) or twice a day) or azithromycin (Zithromax; 500–azithromycin (Zithromax; 500–600mg/day) 600mg/day)

PLUSPLUS ethambutol (Myambutol; ethambutol (Myambutol; 15mg/kg/day) 15mg/kg/day)

PLUS one or more ofPLUS one or more of rifabutin (Mycobutin), rifampin rifabutin (Mycobutin), rifampin (Rifadin, Rimactane), (Rifadin, Rimactane), ciprofloxacin (Cipro) or amikacin ciprofloxacin (Cipro) or amikacin (Amikin) (Amikin)

Risk FactorsRisk Factors::

1.1. AIDS CD4 < 50AIDS CD4 < 502.2. Using an indoor swimming Using an indoor swimming

pool pool 3.3. Consumption of raw or Consumption of raw or

partially cooked fish or partially cooked fish or shellfish, shellfish,

4.4. Bronchoscopy Bronchoscopy 5.5. Treatment with granulocyte Treatment with granulocyte

stimulating factorstimulating factor

AspergillusAspergillus spp pneumonia spp pneumonia

A necrotizing bronchopneumonia with vascular invasion, A necrotizing bronchopneumonia with vascular invasion, leading to the three cardinal features of invasive pulmonary leading to the three cardinal features of invasive pulmonary aspergillosis aspergillosis

1.1. Tissue infarction,Tissue infarction,2.2. Hemorrhage,Hemorrhage,3.3. Metastasis. Metastasis.

Common Presentation: Unresolved Fever with Chest Pain,Common Presentation: Unresolved Fever with Chest Pain,Cough and Hemoptysis.Cough and Hemoptysis.

Risk factors: CD4 count below 50 per microL, Neutropenia, Risk factors: CD4 count below 50 per microL, Neutropenia, Chronic sinusitis and the use of Glucocorticoids, Broad Chronic sinusitis and the use of Glucocorticoids, Broad spectrum antibiotics, or Antineoplastic chemotherapy. spectrum antibiotics, or Antineoplastic chemotherapy.

Copyright © 2007 by the American Roentgen Ray Society

Marchiori, E. et al. Am. J. Roentgenol. 2005;184:757-764

--62-year-old man with AIDS and invasive pulmonary aspergillosis

Typical Halo Appearance

Aspergillus Diagnosis & TreatmentAspergillus Diagnosis & Treatment

Clinical DiagnosisClinical Diagnosis

Can be colonizing organism Can be colonizing organism and therefore not definitive by and therefore not definitive by gram staingram stain

Serum galactomannan Serum galactomannan antigen and beta-D-glucan antigen and beta-D-glucan assays as accepted assays as accepted diagnostics in Europe. diagnostics in Europe.

Ongoing studies in the United Ongoing studies in the United States.States.

PCR-based detection is PCR-based detection is under investigation under investigation

Reverse immunosuppresionReverse immunosuppresionVoriconazole is treatment of Voriconazole is treatment of choice for invasive choice for invasive aspergillus.aspergillus.

Fluconazole has no activity Fluconazole has no activity against aspergillus species.against aspergillus species.

ConclusionConclusionPatient had a re-Patient had a re-bronchoscopy and bronchoscopy and specimens sent for silver specimens sent for silver stain, Fungus culture, HSV stain, Fungus culture, HSV DNA, HHV-8 PCR, CMV DNA, HHV-8 PCR, CMV culture, Acid Fast culture. culture, Acid Fast culture.

MAB blood culture – All MAB blood culture – All negativenegative

Patient continued to Patient continued to deteriorate, CMO and deteriorate, CMO and passed peacefully with sister passed peacefully with sister and partner at bedside.and partner at bedside.