HIV for the EDHIV for the ED

Navpreet Sahsi

Special thanks to Dr. Margriet Greidanus and Dr. James Huffman for their help and allowing use of some of their slides or images for this presentation.

OutlineOutline• Epidemiology• HIV Basics• HIV in the ED, in the post HAART

ERA• Primer on Needlestick injuries

EpidemiologyEpidemiologyWorldwide: 59 million persons

infected, with 20 million deaths worldwide.

US – Currently more than one million individuals currently infected, with greater than fourty thousand new patients diagnosed each year

Canada - ???

How many Canadians have a How many Canadians have a positive HIV Diagnosis? (June positive HIV Diagnosis? (June 2008)2008)

A) 30,000B) 60,000C) 90,000D) 120, 000

AnswerAnswer

B) 60, 000

Public Health Agency of Canada 2008 Surveillance report.

http://www.avert.org/canada-hiv.htmhttp://www.avert.org/canada-hiv.htm

What Province has the What Province has the highest proportion of HIV highest proportion of HIV cases?cases?

A) BCB) AlbertaC) OntarioD) QuebecE) Nunavut

AnswerAnswer

B) Ontario – currently accounts for 39% of the nations HIV cases

BC, Ontario, Quebec, and Alberta account for 85% of our population, and 95% of our HIV cases

Currently 3 reported HIV positive cases in Nunavut since 2002 (epidemic?)

HIV BasicsHIV BasicsFrom Wikipedia: “HIV enters……. macrophages and CD4+

T cells by the adsorption of glycoproteins on its surface to receptors on the target cell followed by fusion of the viral envelope with the cell membrane and the release of the HIV capsid into the cell.[74]

[75]Entry to the cell begins through interaction of the trimeric envelope complex (gp160 spike) and both CD4 and a chemokine receptor (generally either CCR5 or CXCR4, but others are known to interact) on the cell surface.[74][75] gp120 binds to integrin α4β7 activating LFA-1 the central integrin involved in the establishment of virological synapses, which facilitate efficient cell-to-cell spreading of HIV-1.[76] The gp160 spike contains binding domains for both CD4 and chemokine receptors.[74][75] The first step in fusion involves the high-…..”

Ummm……..what?

Better? Better?

The real basicsThe real basics

HIV – single stranded RNA virusPrimarily attacks host cells involved in

immune function – primarily CD4 T cellsMakes copies into host genome’s DNAHigh viral load early – until immune

system kicks in ◦Accounts for acute symptomatic phase

Slowly weakens immune system -> badness

How HIV WorksHow HIV WorksHIV

1. Attachment to host cell

2. Reverse transcriptase makes DNA from the virus’s RNA

3. Integration into host cell’s nucleus

4. Reproduction of viral components

5. Assembly of new HIV viruses

6. Release

BasicsBasicsModes of Transmission

◦Unprotected vaginal or anal intercourse with an infected partner

◦Sharing needles with infected partner

◦Contact with infected blood◦Perinatal transmission

Virus is passed in infected body fluids◦High concentration in blood, semen, vaginal

fluid and breast milk◦Low levels in almost every other fluid (incl.

sweat, urine, csf, tears, bone marrow, alveolar fluid, synovial fluid, amniotic fluid and saliva small likelihood of transmission

Risk Factors- Viral load (higher load = higher risk)- CD4 count < 200 cells/microL- Other STD’s – especially ulcerative lesions

Seroconversion (detectable antibody response to HIV)◦Sources vary, but most sources state

that most patients seroconvert to positive HIV serology in 4 to 10 weeks

◦> 95 % within six months◦Median time to exposure 63 d

Natural HistoryNatural HistoryViral transmissionPrimary HIV infection (acute HIV

infection)SeroconversionClinically latent period (+/-

lymphadenopathy)Early symptomatic HIV infxAIDSAdvanced HIV infx (CD4 < 50)

Natural History of HIV Natural History of HIV InfectionInfection

0 2 2 4 6

Viral L

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CD

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Num

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iral

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Natural History of HIV Natural History of HIV InfectionInfection

0 2 2 4 6

Viral L

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on

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Num

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Clinical Latent Period

AID

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AID

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Acute HIV infectionAcute HIV infectionUsually develop 2 – 4 weeks post

exposure and last for less than 14 days

Presentation is nonspecific and frequently missed◦Diagnosis is missed in up to 75 percent

of patients due to low index of suspicion◦In a small case series from Seattle only

5 of 19 patients (26 %) in HIV surveillance program who sought care from ED’s and walk-in’s were diagnosed with acute HIV infection

What is the most common What is the most common initial presentation with initial presentation with acute HIV?acute HIV?A) FeverB) PharyngitisC) RashD) HeadacheE) Lymphadenopathy

A) Fever - > 90%B) Pharyngitis - > 70 %C) Rash – 40- 80 %D) Headache – 30 – 70 %E) Lymphadenopathy – 40 – 70 %

Presentation very similar to flu-like or mononucleosis-like syndrome.

After six months of infection, plasma viremia reaches a steady state

Viral load is most important predictor of progession of disease in early stages

Natural History of HIV – Natural History of HIV – Clinical Latent PeriodClinical Latent PeriodClinical latent period

◦Generally no findings except for possible lymphadenopathy

◦Persistent generalized lymphadenopathy (PGL) referred to as enlarged lymph nodes involving at least two non-contiguous sites other than inguinal nodes

◦Lymphoid tissue serves as the major reservoir for HIV. Lymphoid tissue traps free virus and infected CD4 T cells

Natural History of HIV - Early Natural History of HIV - Early symptomatic HIV infectionsymptomatic HIV infection

AIDS indicators – can also occur with other disease processes, but are typically more frequent or more severe with an HIV infection

- Thrush- Vaginal candidiasis that is persistent, frequent, or

difficult to manage- Oral hairy leukoplakia- Herpes zoster involving two episodes or more than one

dermatome- Peripheral neuropathy- Bacillary angiomatosis- Cervical dysplasia- Cervical carcinoma in situ- Constitutional symptoms such as fever (38.5°C) or

diarrhea for more than one month- Idiopathic thrombocytopenic purpura- Pelvic inflammatory disease, especially if complicated by

a tubo-ovarian abscess

CandidaCandida

Oral Hairy LeukoplakiaOral Hairy Leukoplakia

Herpes ZosterHerpes Zoster

Probability of developing AIDS Probability of developing AIDS within 3 yearswithin 3 years

Pro

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o A

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(%)

Viral Load (copies/mL)Ann Intern Med

1997;126:946

(N=1,637)(N=1,637)

AIDSAIDS

AIDSAIDS

Diagnosis occurs when a person:1. Has antibodies against HIV in their

bloodAND2. Is diagnosed with one or more AIDS-

defining illnesses

◦ In the US (but not Canada or Europe) the AIDS definition also includes all HIV-infected individuals with a CD4 count lower than 200 cells/μL or a CD4 percentage less than 14%

What are the opportunistic infections that are considered AIDS –defining illnesses?

AIDS-Defining IllnessesAIDS-Defining Illnesses

Candidiasis of esophagus, trachea or lungs

Cervical Cancer (invaisive)

Coccidiomycosis Cryptococcosis Cryptosporidiosis Isosporiosis Cytomegalovirus disease HSV (>1month duration) Disseminated

histoplasmosis HIV encephalopathy Kaposi’s sarcoma

Lymphoma (CNS or Burkitt’s)

Mycobacterium avium complex

Mycobacterium tuberculosis (pulmonary)

Pneumocystis pneumonia Recurrent bacterial

pneumonia Progressive multifocal

leukoencephalopthy Recurrent Salmonella

septicemia Toxoplasmosis of the

brain HIV wasting syndrome

Pneumocystis carinii (PCP)Pneumocystis carinii (PCP)

TuberculosisTuberculosis

Apical infiltrates

Kaposi’s SarcomaKaposi’s Sarcoma

ToxoplasmosisToxoplasmosis

LymphomaLymphoma

Natural History of HIV – Natural History of HIV – AIDSAIDS10% of pts will develop an AIDS

defining diagnosis with a CD4 count above 200/mm3

Most common AIDS diagnosis (prior to HAART)◦P. carinii pneumonia - 42.6%◦Esophageal candidiasis – 15%◦Wasting – 10.7%◦Kaposi’s Sarcoma – 10.7%◦Disseminated M. Avium infection -4.8%◦Tuberculosis – 4.5%

Advanced HIVAdvanced HIVCD4 < 50 Median time of survival 12- 18

months in the absence of ARV’s Presence of end-stage disease –

including disseminated MAC or disseminated CMV

So learning about advanced HIV/AIDS is great, and we all love looking at pictures of Kaposi’s Sarcomas, but does this even matter anymore?

http://www.youtube.comwatchv=DGJDzufJKlc

The HAART EraThe HAART EraRecommended reading

◦Venkat et al. Care of the HIV-Positive Patient in the Emergency Department in the Era of Highly Active Antiretroviral Therapy. Ann Emerg Med. 2008; 52:274-285

Times have changed…Times have changed…In 80’s hospitalizations in HIV

population were mainly due to opportunistic infections and conditions related to patient’s poor immune response to other pathogens

Primarily in patients under 40 years old

In 1993 33.3 % of HIV-related admissions were due to infections caused by opportunistic infections or uncharacterized pneumonia

Living Living longer….longer….Now with the success of HAART,

patients are living longerFor a 20 year old HIV-infected patient,

mean life-expectancy has increased from 9.1 years (+/- 2.3 years) in 1993 to 23.6 years (+/- 4.4 years) in 2002

Now illnesses related to cardiovascular disease, medication adverse effects, and malignancies (mainly lymphoma) have become more prevalent

Who gets HAART?Who gets HAART?Controversial – still debatedFor sure

◦CD4 < 350 cells/microL◦Pregnancy◦HIV – associated nephropathy or

neuropathy◦Co-infection with HBV or HCV

receiving therapy◦History of AIDS-defining illness

??◦Age > 50◦Discordant couples◦CD4 > 350◦Cardiovascular disese

HAART drugsHAART drugsLots of fancy drugs that we never

prescribe…Basically 3 major groups

◦Nucleoside reverse transcriptase inhibitore (NRTIs)

◦Non – NRTIs◦Protease inhibitors

◦Plus some new ones that are being used, but beyond the scope of this talk…..

How NRTI’S WorkHow NRTI’S WorkHIV

Nucleoside reverse transcriptase inhibitors (NRTI’s) latch onto the new strand of DNA that reverse transcriptase is trying to build

How NNRTI’S WorkHow NNRTI’S WorkHIV

Non-nucleoside reverse transcriptase inhibitors (NNRTI’s) hook onto reverse transcriptase and stop it from working

How PI’s WorkHow PI’s WorkHIV

Protease inhibitors (PI’s) prevent final assembly and completion of new HIV viruses within the cell

HAARTHAARTMost patients are on a combination

of drugs from all three classesSide effects many – look up specificsThings of note

◦All ARV’s have potential for hepatotoxicty (any class)

◦Lactic Acidosis◦NNRTI’s and PI’s affect the cytochrome

p450 system – drug interactions!

Cardiovascular DiseaseCardiovascular DiseaseACS

◦All protease inhibitors cause hyperlipidemia, hyperglycemia and truncal obesity

◦Increased time receiving HAART associated with 26% increased relative risk of MI/year

Take home: Consider HIV positive patients on prolonged ARV therapy at risk for ACS often at younger ages

What is the most common What is the most common respiratory pathogen in the respiratory pathogen in the post-HAART era?post-HAART era?

A) Pneumocysitis JiroveciB) C. pneumoniaC) Strep pneumoD) LegionellaE) TB

PulmonaryPulmonaryC) Strep. Pnuemonia most common

pneumonia◦Was PJP in pre-HAART era◦Similar presentation as non-HIV patients◦Can treat similarly if no immune

compromiseHIV is an independant RF for COPD0.5% will have pulmonary

hypertension◦Not related to CD4 count◦Not related to specific HAART therapy

Pneumocystis Jirvoveci Pneumonia◦Prolonged course (2 weeks)◦Typical symptoms of pneumonia -

nonspecific◦CXR interstitial infiltrates in 80%,

otherwise N◦Treatment is TMP-SMX oral or IV

If oral, start 2 DS tabs q8h

RenalRenalARF is now a leading cause of

death in HIV-infected patients◦HIV nephropathy = HAART◦Due to HIV mediated viral or

immunologic disease, as well as treatment-related effects

PI’s associated with urolithiasis◦Rx is the same

CNSCNST. Gondii and C. neoformans were

predominant diseases pre-HAART but less common now

Always CT before LP in workup of new neuro symptoms in patient with prolonged course of HIV infection

Increased risk of CVA – aging population and medication effects

Also think: AIDS dementia, lymphoma, Progressive multifocal leukoencephalopathy (encephalitis)

Peripheral Nervous Peripheral Nervous SystemSystemDistal sensory neuropathies – both

HIV and HAART related (NRTs)◦Typically hypersensitivities to distal

extremities +/- absent ankle reflexes Discontinue meds and treat with gabapentin

and NSAIDSAcute demyelinating

polyneuropathy◦Presents like Guillain-Barre (ascending

muscle weakness and sensory changes)◦Treated with plasmaphoresis

Chronic relapsing demyelinating polyneuropathy

GI and LiverGI and Liver Diarrhea – v. common problem

◦ C. Diff is the most likely bacterial pathogen (up to 36% of patients!)

◦ Assess and treat as you would non-HIV patients If advanced AIDS need to think about

cryptosporidium and microrsporidia – need special stool studies

Co-infection with Hep B/C causes most serious hepatic complications◦ 2-3x more likely to develop chronic liver dz◦ Shorter time to progression of AIDS◦ If HAART meds stopped, severe exacerbations of

Hep B can occur ARV’s can cause an increase in all transaminases

and unconjugated bili with no clinical liver disease

Hematologic and Hematologic and OncologicOncologic Anemia of chronic disease is very common Hemolytic anemia can be severe associated with

certain meds Neutropenia, thrombocytopenia secondary to

disease progression Increased venous thromboembolic events (2-10x

the risk)◦ Coumadin has significant interactions with Protease

inhibitors meds Increased risk of TTP regardless of HAART Increased malignancies – Hodgkin’s, anal cancer,

lung cancer Any person with anal condylomata needs to be

referred for anal cancer screening (HAART hasn’t changed risk)

EndocrineEndocrineProtease inhibitors increase risk

of hyperlipidemia and truncal obesity◦Increased risk of insulin resistance

and DM

PsychiatricPsychiatric Depression 40% - need referral – sig. dec. in

compliance with HAART Demoralization – different from depression in

that it doesn’t have anhedonia◦ Need referral for counselling

AIDS mania - late◦ Present in manic state with no history of previous

disorders◦ Associated with cognitive impairment (AIDS

dementia)◦ R/O meningoencephalitis, need CT, LP

NNRTs can cause a psychosis, nightmares and increased irritability – within first four weeks of therapy◦ need to terminate med only for psychosis, the

other symptoms will resolve

MSK/Rheumatologic MSK/Rheumatologic DiseaseDisease

- Old: HIV – associated arthritis/polymyositis

- Now: Osteoporosis and osteonecrosis most common (usually of the hip)- Think chronic recurrent pain of hip - > surgical

- With HAART increased incidence of infectious complications – septic arthritis, osteomyeltits, diskitis)

- In HAART era, immune syndrome caused by ARV’s has led some patients to develop sarcoidosis (mean time 9 months of therapy)- Symptomatic rx with corticosteroids

OpthoOpthoCMV retinitis reduced by 80%

since onset of HAART therapyAny HIV + patient with any visual

loss or any macular edema needs urgent optho referral

A Quick Primer on A Quick Primer on Needlestick InjuriesNeedlestick Injuries

Hypothetical case:You’re at the end of your shift

and one of your resident collegues pulls you aside in the hallway (let’s call him….I dunno….Kris McKrossin…..with a K)

He tells you that he poked himself in the finger while putting in a central line on a patient a few hours ago and is wondering if he needs post-exposure prophylaxis.

What do you tell “Kris”?

If you don’t know, ask!If you don’t know, ask!Report all casesOH & S Call line 234-7799

◦24 hrs a day/7 days a week

Ask the charge nurse◦Every ED has a pre-printed protocol

on what to do in case of exposures and access to PEP starter kit

If you do get If you do get poked/exposedpoked/exposedRemove the contaminated clothes –

undergarments exceptedAllow immediate bleeding of the

woundWash the injured area well with

soap and water, and apply an antiseptic

If the eyes, nose, or mouth are involved, flush them well with large amounts of water

Southern Alberta Clinic Southern Alberta Clinic GuidelinesGuidelines

1 Is the source known HIV+?◦ Yes: proceed to step 2 of protocol◦ No:

Test source (with consent) using rapid point-of-care HIV test available through CLS at any Emergency Room or Chumir Centre

If negative, and no risk of “window period”, reassure patient

If source unknown or refuses testing and has risks for or symptoms of HIV, proceed to step 2 of protocol

Consider source testing for HBV, HCV – most guidelines suggest testing for this

Rapid HIV TestingRapid HIV Testing Sensitivity and Specificity both >90% Done in the on-site rapid response labs Current turn around time 1 hr 24 min – can take

about 4 hrs from blood draw to get result Realistically takes about 24hrs unless in special

circumstances Confirmed by Western Blot at Prov Lab Consider giving dose of PEP before results arrive

(based on your pre-test probability) CDC now endorsing more liberal use of rapid

point-of-care testing

Southern Alberta Clinic Southern Alberta Clinic GuidelinesGuidelines

2 Timing and Type of Exposure:◦ Assess fluid type, volume, viral titre,

mode of exposure◦ Assess exact timing of exposure◦ If exposure is not considered

infectious for HIV/HBV/HCV (i.e. vomit, feces, etc. without blood –) reassure and arrange f/u if patient desires

◦ If exposure considered potentially infections go to 3

3 Decision:◦ Make a decision for or against PEP

based on risk assessment (these are debatable) HIV + = start PEP HIV – and no risk of source pt being in

“Window period” = don’t start PEP Unknown (source not tested or refuses

testing) = evaluate risk (OHS and protocols binder)

Southern Alberta Clinic Guidelines

Risk AssessmentRisk Assessment-Done by EP / OHS – guidance in protocols and -Done by EP / OHS – guidance in protocols and PEP kitPEP kit

High risk◦ IVDU◦ High risk sexual

behaviour (MSM, sex w/IVDU, multiple sexual partners (3 or more sexual partners/yr w/I past 5 yrs), prostitution

◦ Blood transfusion prior to 1985

◦ Sex w/HIV + person◦ Clinical suspicion of HIV

infections by physicians Prior HIV test HIV as part of a Ddx Unexplained

opportunistic infections (i.e. PCP, toxo, crypto, histo, TB, MAC)

Low Risk◦ HIV -◦ Serology unknown but

answers no to all high risk questions

Unknown◦ Source is not assessed

4 Drug Selection Best to start within 1-2 hrs, consider dose before Rapid

HIV test returns depending on risk of source patient CHR has PEP kits prepared for us Basic Regimen:

◦ If Low risk exposure (unknown source or mucocutaneous exposure)

◦ Combivir: (AZT 300mg + 3TC 150mg) bid Expanded Regimen:

◦ For most percutaneous to known HIV + IN CONTACT WITH ID

◦ Basic Regimen + Nelfinavir 1250mg bid Other:

◦ consider other drugs if source patient is already on antiretrovirals or if source patient is known to have resistant HIV

Southern Alberta Clinic Guidelines

Southern Alberta Clinic Southern Alberta Clinic GuidelinesGuidelines

5 Duration of Prophylaxis:◦Start ASAP and continue for 4 weeks

6 Discuss adverse reactions w/patient

ED physician to order baseline CBC, diff., ALT

HBV, HCV, HIV serology

Follow up?

Follow UpFollow UpOccupational exposures are sent

to Odyssey Travel and Tropical Medicine Clinic – 14th ST NW – Dr. Rudy Zimmer

Employee to make own appointment – phone # in the ED

MD to fax referral form to Dr. Zimmer

ReferencesReferences Venkat et al. Care of the HIV-Positive Patient in the Emergency

Department in the Era of Highly Active Antiretroviral Therapy. Ann Emerg Med. 2008; 52:274-285

Rothman et al. Preventive Care in the Emergency Department: Should Emergency Departments Conduct Routine HIV Screening? Acad Emerg Med 2003; 10; 278- 285.

Rothman et al. HIV and complications in Emergency Medicine. Emerg Med Clin N Am 2008; 26; 367-387.

Emergency Med Reports HIV Positive Patient in the ED Part I and II, Vol 27:9, Apr. 2006

FMC ED Charge Nurse Manual (PDF File) Management of Health Care workers exposed to HIV.

www.uptodate.com When to Initiate Antiretroviral therapy in HIV-infected patients

www.uptodate.com Primary HIV-1 Infection: Diagosis and Treatment

www.uptodate.com Tintinalli, J. Emergency Medicine: A comprehensive study guide 6th

Ed. 2004. pgs. 925-935. Google Images Dr. Margriet Gredanus and Dr. James Huffman