The HIV-Infected Adult Patient In February 2016

Volume 18, Number 2

The Emergency Department: The Authors

David L. Gutteridge, MD, MPH

Changing Landscape Of Disease

Department of Emergency Medicine, Icahn School of Medicine at Mount
Sinai, New York, NY
Daniel J. Egan, MD
Associate Professor, Department of Emergency Medicine, Program
Abstract Director, Emergency Medicine Residency, Mount Sinai St. Luke’s
Roosevelt, New York, NY

The care of the HIV-infected patient in the emergency department Peer Reviewers

has changed since the development of highly active antiretroviral
therapy. This therapy has resulted in longer life expectancies and
increased quality of life for HIV-infected patients, and in cases of
treatment compliance and success, virtual elimination of AIDS-
associated opportunistic infections. As a result, the emergency cli-
nician is now more often confronted with adverse events related
to medication and the diseases associated with aging and chronic
disease. This issue focuses on the differences in evaluation of HIV
patients on long-term therapy and patients with medication non-
compliance and low CD4 counts, as well as recognition of life-
threatening and rare opportunistic infections. Disease processes
related to the effect of longstanding HIV infection, even with
good control, on many organ systems are addressed.
Andy Jagoda, MD, FACEP
Professor and Chair, Department of Emergency Medicine, Icahn School
of Medicine at Mount Sinai, New York, NY; Medical Director, Mount Sinai
Hospital, New York, NY
Roland C. Merchant, MD, MPH, ScD
Associate Professor, Emergency Medicine and Epidemiology, Brown
University, Rhode Island Hospital, Providence, RI
CME Objectives
Upon completion of the article, you should be able to:
1. Describe the pathophysiology of disease processes unique to the
initiation of and long-term treatment with antiretroviral drugs.
2. Recognize common side effects of antiretroviral drugs.
3. Risk stratify patients with common presentations based on their HIV
status and whether they are on highly active antiretroviral therapy.
4. Recognize the more common system-based diseases and problems
encountered in patients on highly active antiretroviral therapy.
Prior to beginning this activity, see “Physician CME Information”
on the back page.

Editor-In-Chief Daniel J. Egan, MD Eric Legome, MD Robert Schiller, MD Research Editor

Andy Jagoda, MD, FACEP
Professor and Chair, Department of
Emergency Medicine, Icahn School
of Medicine at Mount Sinai, Medical
Director, Mount Sinai Hospital, New
York, NY
Associate Editor-In-Chief
Kaushal Shah, MD, FACEP
Associate Professor, Department of
Emergency Medicine, Icahn School
of Medicine at Mount Sinai, New
York, NY
Editorial Board
Saadia Akhtar, MD
Associate Professor, Department of
Emergency Medicine, Associate Dean Steven A. Godwin, MD, FACEP
for Graduate Medical Education,
Program Director, Emergency
Medicine Residency, Mount Sinai
Beth Israel, New York, NY
William J. Brady, MD
Professor of Emergency Medicine
and Medicine, Chair, Medical
Emergency Response Committee,
Medical Director, Emergency
Management, University of Virginia
Medical Center, Charlottesville, VA
Calvin A. Brown III, MD
Director of Physician Compliance,
Credentialing and Urgent Care
Services, Department of Emergency
Medicine, Brigham and Women's
Hospital, Boston, MA
Peter DeBlieux, MD Assistant Clinical Professor,
Professor of Clinical Medicine,
Interim Public Hospital Director
of Emergency Medicine Services,
Louisiana State University Health
Science Center, New Orleans, LA
Associate Professor, Department
of Emergency Medicine, Program
Director, Emergency Medicine
Residency, Mount Sinai St. Luke's
Roosevelt, New York, NY
Nicholas Genes, MD, PhD
Assistant Professor, Department of
Emergency Medicine, Icahn School
of Medicine at Mount Sinai, New
York, NY
Michael A. Gibbs, MD, FACEP
Professor and Chair, Department
of Emergency Medicine, Carolinas
Medical Center, University of North
Carolina School of Medicine, Chapel
Hill, NC
Professor and Chair, Department
of Emergency Medicine, Assistant
Dean, Simulation Education,
University of Florida COM-
Jacksonville, Jacksonville, FL
Gregory L. Henry, MD, FACEP
Clinical Professor, Department of
Emergency Medicine, University
of Michigan Medical School; CEO,
Medical Practice Risk Assessment,
Inc., Ann Arbor, MI
John M. Howell, MD, FACEP
Clinical Professor of Emergency
Medicine, George Washington
University, Washington, DC; Director
of Academic Affairs, Best Practices,
Inc, Inova Fairfax Hospital, Falls
Church, VA
Shkelzen Hoxhaj, MD, MPH, MBA
Chief of Emergency Medicine, Baylor
College of Medicine, Houston, TX
Chief of Emergency Medicine, Chair, Department of Family Medicine,
King’s County Hospital; Professor of Beth Israel Medical Center; Senior Andrea Duca, MD
Emergency Medicine Residency,
Clinical Emergency Medicine, SUNY Faculty, Family Medicine and
Downstate College of Medicine, Community Health, Icahn School of Università Vita-Salute San Raffaele
of Milan, Italy
Brooklyn, NY Medicine at Mount Sinai, New York, NY
Keith A. Marill, MD Scott Silvers, MD, FACEP International Editors
Research Faculty, Department of Chair, Department of Emergency
Peter Cameron, MD
Emergency Medicine, University Medicine, Mayo Clinic, Jacksonville, FL
Academic Director, The Alfred
of Pittsburgh Medical Center,
Corey M. Slovis, MD, FACP, FACEP Emergency and Trauma Centre,
Pittsburgh, PA
Professor and Chair, Department Monash University, Melbourne,
Charles V. Pollack Jr., MA, MD,
of Emergency Medicine, Vanderbilt Australia
FACEP
University Medical Center, Nashville, TN
Professor and Chair, Department of Giorgio Carbone, MD
Ron M. Walls, MD Chief, Department of Emergency
Emergency Medicine, Pennsylvania
Hospital, Perelman School of Professor and Chair, Department of Medicine Ospedale Gradenigo,
Emergency Medicine, Brigham and Torino, Italy
Medicine, University of Pennsylvania,
Philadelphia, PA Women's Hospital, Harvard Medical
Suzanne Y.G. Peeters, MD
School, Boston, MA
Michael S. Radeos, MD, MPH Emergency Medicine Residency
Director, Haga Teaching Hospital,
Assistant Professor of Emergency Critical Care Editors The Hague, The Netherlands
Medicine, Weill Medical College
of Cornell University, New York; William A. Knight IV, MD, FACEP Hugo Peralta, MD
Research Director, Department of Associate Professor of Emergency Chair of Emergency Services,
Medicine and Neurosurgery, Medical
Emergency Medicine, New York Hospital Italiano, Buenos Aires,
Hospital Queens, Flushing, NY Director, EM Midlevel Provider Argentina
Program, Associate Medical Director,
Ali S. Raja, MD, MBA, MPH Neuroscience ICU, University of Dhanadol Rojanasarntikul, MD
Vice-Chair, Emergency Medicine, Cincinnati, Cincinnati, OH Attending Physician, Emergency
Massachusetts General Hospital, Medicine, King Chulalongkorn
Scott D. Weingart, MD, FCCM
Boston, MA Memorial Hospital, Thai Red Cross,
Associate Professor of Emergency
Robert L. Rogers, MD, FACEP, Thailand; Faculty of Medicine,
Medicine, Director, Division of ED Chulalongkorn University, Thailand
FAAEM, FACP Critical Care, Icahn School of Medicine
Assistant Professor of Emergency
at Mount Sinai, New York, NY Stephen H. Thomas, MD, MPH
Medicine, The University of Professor and Chairman, Emergency
Maryland School of Medicine, Senior Research Editors Medicine, Hamad Medical Corporation
Baltimore, MD and Weill Cornell Medical College,
James Damilini, PharmD, BCPS
Alfred Sacchetti, MD, FACEP Qatar; Emergency Physician-in-Chief,
Clinical Pharmacist, Emergency
Hamad General Hospital, Doha, Qatar
Room, St. Joseph’s Hospital and
Department of Emergency Medicine,
Medical Center, Phoenix, AZ
Thomas Jefferson University,
Philadelphia, PA Joseph D. Toscano, MD
Chairman, Department of Emergency
Medicine, San Ramon Regional
Medical Center, San Ramon, CA
Case Presentations
You arrive for your ED shift and are presented with 3
HIV-infected patients with various chief complaints. The
first patient is a 28-year-old man with 1 day of right flank
pain, nausea, vomiting, and hematuria. He had a kidney
stone a year ago with identical pain, and a point-of-care
ultrasound shows asymmetric hydronephrosis; however, a
nonenhanced CT scan demonstrates hydronephrosis and
hydroureter without a stone. You wonder if the CT elimi-
nates an impacted stone or if there is another explanation.
The second patient is a 42-year-old HIV-infected
woman complaining of as many as 3 episodes a day of
diarrhea for the past 3 weeks. She denies pain, melena,
rectal bleeding, and fevers. Her laboratory test results are
unremarkable. You wonder if additional testing is needed
and whether sending her home is appropriate.
The third patient presents because her family has
noticed that she has been acting increasingly “sad.” She
denies any suicidal or homicidal ideation, but does cor-
roborate that since initiation of an SSRI antidepressant
drug 6 months ago, she has not noticed any improvement
in her mood. In the absence of suicidal ideation, you won-
der if she can be sent home.
You are reminded that caring for the HIV-infected
patient is not so simple, and you realize quickly that you
are dealing with 3 very different presentations related to
the same disease and must prioritize where to begin.
Introduction
The human immunodeficiency virus (HIV) causes a
progressive failure of the immune system, ultimately
leading to acquired immunodeficiency syndrome
(AIDS) in the absence of treatment. Although under
different nomenclature, AIDS was first described in
the early 1980s when clusters of patients developed
opportunistic infections (OIs) not seen in patients
with intact immune systems. HIV has spread to every
country in the world, creating a global pandemic. In
2012, there were 35.3 million people living with HIV
worldwide and 2.3 million new diagnoses that year.1
The development of highly active antiretroviral
therapy (HAART) in 1996 dramatically increased
life expectancy for HIV-infected patients. Due to
the effectiveness of HAART, by the early 2000s, life
expectancy of HIV-infected patients in developed
countries was equivalent to that of comparable per-
sons who were not HIV-infected.2,3
Current guidelines from the United States
Department of Health and Human Services recom-
mend the treatment of all HIV-infected patients
with antiretroviral medications (ARVs).4 These
current recommendations are based on evidence
that ARVs reduce the risk of disease progression in
all patients with CD4 T lymphocyte (CD4) count
< 350 cells/mm3, CD4 count 350 to 500 cells/mm3,
and CD4 count > 500 cells/mm3. This recommen-
Copyright © 2016 EB Medicine. All rights reserved. 2
dation is a change from prior guidelines, which
recommended therapy only for patients with
lower CD4 counts. The guidelines are also based
on evidence that treatment decreases the risk of
transmission, and that patients with undetectable
HIV viral loads are at exceedingly low risk for
transmitting the virus to others.5
In addition to improving life expectancy,
HAART has also changed the epidemiology of
conditions affecting HIV-infected patients. In the
beginning of the epidemic, HIV patients generally
presented with infectious complications of their
advanced disease. These included OIs such as Pneu-
mocystis jiroveci pneumonia and Kaposi sarcoma.
Now, patients more commonly present with compli-
cations unrelated to OIs, including cardiovascular,
hepatic, and kidney disease, as well as HIV-related
malignancies and adverse effects from medication.5,6
The spectrum of presenting complaints is associated
with patient compliance with treatment. OIs are still
seen in patients with undiagnosed infection present-
ing with advanced disease and those with financial,
social, or other barriers to medication compliance.
This changing epidemiology of HIV complica-
tions poses a particular challenge for emergency cli-
nicians, who should be familiar with these presenta-
tions as well as the presentation of OIs. This issue of
Emergency Medicine Practice reviews the emergency
complications of long-term HIV infection, especially
noninfectious conditions and complications common
in the HAART-adherent HIV patient.
Selected Abbreviations
AIDS Acquired immunodeficiency syndrome
ARV Antiretroviral
AZT/ZDV Zidovudine
HAART Highly active antiretroviral therapy
HIV Human immunodeficiency virus
NNRTI Nonnucleoside reverse transcriptase inhibitor
NRTI Nucleoside reverse transcriptase inhibitor
NtRTI Nucleotide reverse transcriptase inhibitor
OI Opportunistic infection
PEP Postexposure prophylaxis
PI Protease inhibitor
Critical Appraisal Of The Literature
PubMed and the Cochrane Database of System-
atic Reviews were searched for English-language
articles related to the management of HIV/AIDS.
Attention was focused on articles relevant to the
emergency clinician, those published after 1996 (to
coincide with the advent of HAART), and on articles
that discussed the effects of chronic HIV infection
and HAART adverse events. Search terms included
HIV, AIDS, combination antiretroviral therapy, highly
active antiretroviral therapy, and immune reconstitution
Reprints: www.ebmedicine.net/empissues
inflammatory syndrome. Because of the large num-
ber of articles retrieved in these searches, the initial
focus was on review articles with cross-referencing
primary literature cited in the bibliographies. Rel-
evant guidelines by the World Health Organization,
the United States Department of Health and Human
Services, and the American College of Emergency
Physicians were also reviewed.
Now, nearly 20 years after the advent of
HAART, considerable literature exists on the subject
of HIV both in terms of the OIs patients experience
and the chronic effects of longstanding illness and
treatment. This literature provides strong evidence
to support the practice recommendations made in
this article.
Epidemiology And Pathophysiology
In 2012, there were an estimated 1.2 million persons
in the United States aged > 12 years infected with
HIV. This estimate includes approximately 160,000
persons (14%) who were unaware of their diag-
nosis.7 The high prevalence of undiagnosed HIV
underscores the importance of routine HIV testing.
Based on 2009-2010 National Hospital Ambulatory
Medical Care Survey data, HIV-infected patients
accounted for 5 in 1000 emergency department (ED)
visits. Although they had similar acuity to non–HIV-
infected patients, they received more diagnostic test-
ing, had longer lengths of stay, and were more likely
to be admitted.8
In order to become infected with HIV, an indi-
vidual must be exposed to an infected body fluid,
typically through either direct inoculation into the
bloodstream or via a disrupted mucosal barrier. As a
medium, blood carries the highest risk of infection;
however, exposure to other fluids such as semen,
vaginal secretions, breast milk, and cerebrospinal
fluid also carry risk. Risk of infection is determined
by 2 key factors: the viral load of the source patient
and the method of exposure. Several days after
infection, the virus moves beyond the local site of in-
fection into the bloodstream with rapid replication.
Approximately 75% to 90% of patients experience
an acute illness during this time. Patients develop
a fever, with additional symptoms typical of many
viral syndromes including lymphadenopathy, sore
throat, and gastrointestinal symptoms (such as vom-
iting and diarrhea). Some more-distinctive features
include genital or mucocutaneous ulcers and a rela-
tively nondescript macular rash that mimics a viral
exanthem often seen in children with viral illnesses.
The syndrome typically lasts for weeks, and patients
seek evaluation by a medical provider, often in the
ED. There is a notable absence of pulmonary symp-
toms during the illness, and this may help clinicians
in their diagnostic approach to the febrile patient.
This constellation of signs and symptoms is known
February 2016 • www.ebmedicine.net
by several names, including acute seroconversion,
primary HIV infection, or acute retroviral syndrome.
During the seroconversion syndrome, there may
be an acute drop in CD4 count (leading, rarely, to an
OI), which typically rebounds when the body gains
some control over the virus. The diagnosis of acute
seroconversion is challenging, because current rapid
HIV antibody testing technology may not detect the
presence of the infection. Fourth-generation tests
that combine detection of the HIV antibody as well
as the p24 antigen on the surface of HIV identify in-
fection as early as 2 weeks after exposure. However,
with negative rapid testing and with a diagnosis of
an acute HIV infection suspected, an HIV viral load
must be obtained. Diagnosis is critical, as patients
with acute infection have extremely high viral loads
and are more infectious than those with chronic in-
fection. Additionally, identification of acute infection
allows for prompt referral to an HIV clinician, allow-
ing initiation of ARV therapy. After the acute illness
is over, patients experience a period of chronic (or
latent) HIV infection without AIDS. AIDS is defined
by a CD4 count < 200 cells/mm3 or development
of certain OIs or cancers. The average time from
HIV infection to a CD4 count < 200 cells/mm3 is 8
to 10 years. Most individuals remain asymptomatic
during this chronic (or latent) phase, although many
have lymphadenopathy. Considering the high in-
fectivity and then clinical silence, if the diagnosis is
missed, emergency clinicians must maintain a high
index of suspicion for this illness in patients present-
ing with typical features and risk factors for HIV
exposure in the weeks preceding their evaluation.
Although patients may survive for years with-
out developing OIs, chronic infection with the virus
in the absence of HAART is not without detrimen-
tal effects on the body. Infection causes a chronic
inflammatory state, which may predispose patients
to numerous conditions, including coronary artery
disease, venous thromboembolism, and chronic
obstructive pulmonary disease. Once patients begin
treatment with HAART, measurable inflamma-
tory markers decrease, as does the risk for adverse
sequelae from the HIV infection itself. However, pa-
tients taking HAART are at risk for adverse medica-
tion effects as well as regular age-related conditions
that have become more prevalent as HIV-infected
patients live longer.
Prehospital Care
The primary goal for providers in the prehospital
care of the HIV-infected patient is safe transfer to the
receiving facility and careful attention to personal
protection. Resuscitation and stabilization of the
HIV-infected patient follows the same principles as a
non–HIV-infected individual. High-risk procedures
for exposure to bodily fluids occur often, and the
3 Mobile app access: www.ebmedicine.net/app
prehospital provider must take caution for his or
her own safety, strictly adhering to universal pre-
Table 1. Major Adverse Effects Of
cautions. In the event that a blood or body fluid
Antiretroviral Medications4
exposure does occur, the provider should seek Medication Adverse Effects
immediate care. Treatment with postexposure pro- Nucleoside Reverse Transcriptase Inhibitors
phylaxis (PEP) (a 28-day course of treatment with
HIV medication) is effective at decreasing rates of Abacavir Hypersensitivity reaction, Stevens-Johnson
syndrome, lactic acidosis, increased risk of
HIV acquisition.
myocardial infarction
Didanosine Stevens-Johnson syndrome, lactic acidosis,
Emergency Department Evaluation pancreatitis, peripheral neuropathy
Emtricitabine Lactic acidosis, hyperpigmentation/skin discol-
History oration
Chronic HIV infection can affect nearly every organ Lamivudine Lactic acidosis
system, highlighting the importance of a thorough
Stavudine Lactic acidosis, pancreatitis, peripheral neuropathy
history and physical examination. First, providers
should evaluate the status of the HIV infection (eg, Tenofovir* Lactic acidosis, Fanconi syndrome, accelerated
CD4 count and viral load), the treatment regimen, osteoporosis
and the patient's medication compliance. After an Zidovudine Stevens-Johnson syndrome, lactic acidosis, bone
overall sense of disease status is obtained, emer- marrow suppression
gency clinicians should focus on evaluation of the Nonnucleoside Reverse Transcriptase Inhibitors
chief complaint and its relevance to HIV infection or Delavirdine Stevens-Johnson syndrome, transaminitis
treatment taken for the HIV infection.
Initial questions for an HIV-infected patient Efavirenz Stevens-Johnson syndrome, psychosis, depression

include inquiring about the patient’s most recent Etravirine Stevens-Johnson syndrome, hypersensitivity reac-
CD4 count, viral load (or at least whether the viral tions
load is undetectable), and any recent travel history Nevirapine Stevens-Johnson syndrome, hepatic necrosis
or exposure to sick contacts. Asking about a pa- Rilpivirine Stevens-Johnson syndrome, depression
tient’s prior OIs is also important, as patients may
Protease Inhibitors
have sequelae from OIs that alter their physical
examination. If the patient is on HAART, determine Atazanavir Hyperbilirubinemia (indirect), PR interval prolon-
the specific drugs taken, the patient’s compliance, gation/atrioventricular block
and ask about the characteristic side-effect profiles Darunavir Gastrointestinal upset, sulfonamide hypersensitiv-
of some medications. (See Table 1.) These ques- ity, hepatotoxicity, Stevens-Johnson syndrome
tions help frame an understanding of the patient’s Fosamprenavir Rash, sulfonamide hypersensitivity, transaminitis
baseline HIV infection status. Indinavir Nephrotoxicity, urolithiasis
Questions related to the patient’s chief com-
Lopinavir Pancreatitis, PR and QT interval prolongation,
plaint should be guided by whether or not the transaminitis, gastrointestinal intolerance
patient is under the care of a clinician for his or her
Nelfinavir Gastrointestinal intolerance
HIV infection and is compliant with the prescribed
medication regimen. Patients unaware of their CD4 Ritonavir Gastrointestinal intolerance, metabolic syndrome,
count or viral load or who are not engaged in their paresthesia (circumoral and extremities),
asthenia
care should be considered at higher risk for OIs and
other complications of AIDS. Therefore, a thorough Saquinavir Metabolic syndrome, PR and QT interval prolon-
gation
history of these patients includes questions regard-
ing infectious symptoms such as fevers, chills, and Tipranavir Hepatotoxicity, intracranial hemorrhage, skin rash
diaphoresis. Patients compliant with treatment Integrase Inhibitors
regimens are at higher risk for conditions related to
Dolutegravir Hypersensitivity reactions
chronic infection and adverse reactions from medi-
cation. A thorough review of systems may uncover Elvitegravir Nephrotoxicity, gastrointestinal intolerance
symptoms related to chronic infection that the pa- Raltegravir Stevens-Johnson syndrome, creatine phosphoki-
tient may not have thought relevant to their present- nase elevation, pyrexia
ing complaint (eg, changes in skin, sleep, bowel or Fusion/Entry Inhibitors
bladder habits, or psychiatric disturbance).
Enfuvirtide Hypersensitivity reaction, increased incidence of
pneumonia
Physical Examination
Maraviroc Hepatotoxicity, abdominal pain, pyrexia, upper
A complete physical examination is critical for respiratory tract infections
patients with HIV. Physical examination findings *Nucleotide reverse transcriptase inhibitor.
related to specific conditions are discussed in the fol-

Copyright © 2016 EB Medicine. All rights reserved. 4 Reprints: www.ebmedicine.net/empissues

lowing sections. Because HIV has many dermatolog-
ic manifestations, a comprehensive skin examination
should be included in addition to a complaint-based
physical examination.
Diagnostic Testing
Laboratory Testing
In general, laboratory testing plays an important
role in the screening and diagnosis of HIV-related
metabolic and infectious diseases. A study published
in 2013 suggested that HIV-infected patients re-
ceived 4.5 laboratory tests per ED visit compared to
3.5 tests for the non–HIV-infected individual.8 These
tests included complete blood count, basic metabolic
panel, and hepatic function testing. Lactic acidosis
is a complication of nucleoside reverse transcriptase
inhibitor (NRTI) use and, when acutely worsened,
is associated with higher mortality. Serum lactic
acid measurement is appropriate in patients with
an anion gap metabolic acidosis or severe illness.
HIV-infected patients are not only tested more often
than noninfected patients, but are admitted more
frequently.8 Therefore, it appears that having a lower
threshold for testing is appropriate in these patients.
When infectious complications are suspected,
appropriate cultures (sometimes for atypical
organisms or OIs) should be ordered. If recent
HIV-specific testing results are not available, the
emergency clinician can order a CD4 count and
viral load; however, timely results are not typical-
ly available for decision-making. CD4 counts and
viral load results help to narrow the differential
diagnosis in HIV-infected patients. In cases where
patients have not had or do not know these val-
ues, an absolute lymphocyte count may be used as
a surrogate for CD4 count.9 An absolute lympho-
cyte count < 950 cells/mm3 is associated with a
total CD4 count < 200 cells/mm3 (sensitivity, 76%;
95% confidence interval [CI] 73%-79%; specificity,
93%; 95% CI, 87%-96%; positive likelihood ratio,
10.1; 95% CI, 8.2-14).10
HIV testing should be conducted in individuals
who might be infected with HIV if they show signs or
symptoms of diagnoses consistent with OIs or AIDS-
related complications. Rapid HIV antibody testing is
available using either oral swabs or blood samples.
Most currently available HIV antibody tests have sen-
sitivities of 100% and specificities > 99%. Fourth-gen-
eration HIV tests identify both antibodies as well as
the p24 antigen on the surface of HIV, which appears
to permit earlier diagnosis of an HIV infection. If an
acute HIV infection is suspected, then measurement
of a viral load can help to make the diagnosis.
February 2016 • www.ebmedicine.net
Imaging
Radiologic imaging tests should be directed at
the patient’s complaints and immune status. The
emergency clinician should have a low bar for imag-
ing, especially low-risk and low-cost tests (such as
x-ray and ultrasound), where appropriate. Other
modalities such as computed tomography (CT) and
magnetic resonance imaging (MRI) should also be
used, when appropriate. For example, an immu-
nocompetent HIV-infected patient with headache
probably does not need a CT of the brain; however,
with decreasing CD4 counts, the chance of OIs or
malignancy in the brain increases, and neuroimag-
ing is indicated.
Medication Side Effects
Highly Active Antiretroviral Therapy
The first promising antiretroviral medication against
HIV was the NRTI, zidovudine (AZT/ZDV), which
was approved by the United States Food and Drug
Administration (FDA) in 1987. In the years follow-
ing, several more NRTIs were developed; however,
the virus’s rapid rate of mutation created drug
resistance, and mortality remained high. In 1996, the
addition of protease inhibitors (PIs) revolutionized
HIV treatment. Two landmark studies demonstrated
a 60% to 80% decrease in AIDS, associated hospital-
ization, and mortality in patients treated with this
drug combination, HAART.11-13 In addition, non-
nucleoside reverse transcriptase inhibitors (NNRTI),
integrase inhibitors, fusion inhibitors, entry inhibi-
tors, and pharmacokinetic enhancers have been
introduced as treatment, each directed at a different
stage of viral reproduction. Medications are often
administered in combination therapy through single
pills. This section will discuss each of these drug
classes and some of the more common adverse reac-
tions and side effects associated with each.
Nucleoside Reverse Transcriptase Inhibitors And
Nucleotide Reverse Transcriptase Inhibitors
The NRTIs and nucleotide reverse transcriptase in-
hibitors (NtRTIs) inhibit reverse transcription of HIV
RNA into DNA, thereby preventing viral replica-
tion. These classes of medications are relatively well
tolerated and have a mild side-effect profile, includ-
ing gastrointestinal upset, headache, and insomnia.
The most severe toxic effect is dose-dependent bone
marrow suppression, causing anemia and leukope-
nia.14 Transaminitis and severe lactic acidosis have
also been reported and are more common in patients
with liver disease.
Abacavir, one of the most commonly prescribed
NRTIs, is associated with a potentially severe hyper-
sensitivity reaction in 3% to 5% of patients. Certain
HLA alleles are susceptible to this reaction and
guidelines have been developed for screening and
5 Mobile app access: www.ebmedicine.net/app
dosing before prescribing this medication, which re-
duces or eliminates its occurrence.15,16 Symptoms of
the hypersensitivity reaction include fever, rash, and
gastrointestinal and respiratory symptoms, which
usually occur within the first 6 weeks of drug expo-
sure. Abacavir is also associated with an increased
risk of myocardial infarction in patients with risk
factors for cardiovascular disease.17
For patients with liver disease who are taking
NRTIs, discontinuation of agents effective against
both HIV and hepatitis B virus (eg, emtricitabine,
lamivudine, and tenofovir) can precipitate a severe
and sometimes fatal flare in hepatitis. When present-
ed with this clinical concern, the emergency clinician
should provide supportive care and consult an infec-
tious disease specialist for treatment options.
Tenofovir, another commonly prescribed NRTI, is
associated with development of Fanconi syndrome in
some patients.18 Patients with impaired renal function
prior to initiation of the drug are most at risk. Patients
with this syndrome can develop polyuria, polydipsia,
and dehydration. Laboratory tests may demonstrate
acidemia, hypochloremia, hypokalemia, and hypo-
phosphatemia due to loss of bicarbonate, glucose,
amino acids, and phosphate in the urine. Urinalysis
demonstrates glucosuria and proteinuria. Tenofovir
can also cause bone density loss and fractures, either
alone or as part of Fanconi syndrome. The syndrome
is usually avoided by stopping tenofovir at the time
of abnormal creatinine measurements.
Some medications in this class have less com-
mon, but important, side effects. According to
animal studies, AZT/ZDV may cause endothelial
dysfunction leading to cardiovascular complica-
tions.19 Didanosine and stavudine have been associ-
ated with a rare incidence of pancreatitis, which can
be fatal and has led to an FDA black box warning.
Nonnucleoside Reverse Transcriptase Inhibitors
NNRTIs also inhibit HIV reverse transcriptase. Ex-
amples of NNRTIs include nevirapine, efavirenz, etra-
virine, and rilpivirine. Efavirenz is associated with
vivid dreams, nightmares, insomnia, and confusion,
which often resolve after the first several weeks of
treatment.20 However, more-severe neuropsychiatric
complications, including severe psychosis, have been
reported, and for this reason, efavirenz is often avoid-
ed in patients with a psychiatric history. Immediate
discontinuation of the medication is recommended if
such severe psychosis occurs. Rarely, rilpivirine is also
associated with insomnia and depression.
Rash, gastrointestinal upset, headache, and diz-
ziness are common with all medications in this class.
Infrequently (though more commonly with nevi-
rapine), patients can experience Stevens-Johnson
syndrome, toxic epidermal necrolysis, or erythema
multiforme. Nevirapine has also been associated
with liver injury and failure, which led to an FDA
black box warning in 2000. This complication is most
Copyright © 2016 EB Medicine. All rights reserved. 6
frequent in the first 6 weeks of treatment and in pa-
tients with a history of chronic hepatitis and in male
patients with CD4 counts > 400/mm3.21
Protease Inhibitors
PIs prevent budding of the mature HIV virion from
the host membrane, making the virus largely nonin-
fectious. The most commonly used PIs are atazana-
vir, darunavir, lopinavir/ritonavir, and nelfinavir.
Common side effects associated with PIs are mild
gastrointestinal upset, including nausea, diarrhea,
and abdominal discomfort. Other potentially more
severe metabolic alterations include lipodystrophy,
dyslipidemia, hypertriglyceridemia, and type 2
diabetes mellitus.22 Rarely, hypertriglyceridemia
can precipitate pancreatitis. Atazanavir is associated
with hyperbilirubinemia and jaundice, which may
prompt patients to present to the ED; however, this
condition is not dangerous and resolves when the
drug is discontinued.
Many of the PIs inhibit, and some induce,
isoforms of the cytochrome P 450 enzyme system.
As a result, numerous other classes of medications
interact with PIs, including proton pump inhibi-
tors, anticoagulants, HMGCoA reductase inhibi-
tors, corticosteroids, antiarrhythmics, antiepileptics,
antimalarials, and antidepressants. Therefore, it
is imperative to cross-check interactions prior to
administering or prescribing other medications to
patients taking PIs.4,23
Integrase Inhibitors
Integrase inhibitors, first approved by the FDA in
2007, prevent the incorporation of viral DNA into
the human host DNA. Examples of integrase inhibi-
tors include raltegravir, dolutegravir, and elvitegra-
vir. This class of medications is usually well toler-
ated, with side effects usually mild and including
nausea and headache.
Fusion Inhibitors
In order for HIV to gain entry into the host CD4 cell,
glycoprotein 120 on the surface of HIV must attach
to host receptors and other glycoproteins, ultimately
allowing the cells to fuse. Currently, the only fusion
(sometimes called entry) inhibitors available are
enfuvirtide and maraviroc. Enfuvirtide is admin-
istered by injection only because the acidic pH of
the stomach destroys the protein component of this
medication. Side effects are primarily limited to local
erythema and nodules at the injection site. Rarely,
patients develop neutropenia.
System-Based Disease And Medication Effects
Cardiovascular Disease
As the life expectancy of HIV-infected patients has
increased, so have observed rates of traditional age-
Reprints: www.ebmedicine.net/empissues
related conditions (such as cardiovascular disease)
increased among this population. A recent study
estimated the increased relative risk of myocardial
infarction among HIV-infected persons to be 1.75
(95% CI, 1.51-2.02) compared to patients not HIV-
infected.24 The pathophysiology of this increase
involves not only traditional risk factors such as
age and smoking, but also HAART. As mentioned
previously, HAART causes metabolic side effects
that also likely contribute the increased risk of car-
diovascular disease.17,25-27
Pulmonary Disease
Prior to HAART, Pneumocystis pneumonia used to be
one of the most common opportunistic pulmonary
infections. Patients with Pneumocystis pneumonia
classically present with an indolent, nonproductive
cough and exertional dyspnea. On x-ray, a perihilar
or “batwing” infiltrate is seen. (See Figure 1.) Lac-
tate dehydrogenase (LDH) is typically elevated in
patients with Pneumocystis pneumonia, and a normal
value is helpful in ruling out the disease.28 Patients
infected with HIV are at increased risk of tubercu-
losis (TB), (both novel infection and reactivation)
after diagnosis with HIV because of the depletion of
TB-specific T-cells. With poorly controlled HIV infec-
tion, the risk of TB increases. In the developed world
(where there are lower rates of TB in general), the
Figure 1. Chest X-Ray Of Pneumocystis
jiroveci Pneumonia
Arrows point to perihilar (“batwing”) infiltrate.
Image courtesy of Mount Sinai St. Luke's Hospital, New York, NY.
February 2016 • www.ebmedicine.net
disease is not seen as frequently, but it must remain
on the differential in HIV-infected patients with pos-
sible exposures.
Today, patients with well-controlled HIV on
HAART more commonly develop the traditional
pulmonary infections of immunocompetent pa-
tients, of which, Streptococcus pneumonia is most
common.29 Treatment for common pneumonias is
the same as for non–HIV-infected patients, using
antibiotics and fluid resuscitation or other sup-
portive measures. Patients with immunosuppres-
sive disease are at risk for drug-resistant organ-
isms, and the emergency clinician should con-
sider expanding therapy in those patients whose
disease is not well-controlled.
Guidance on the disposition of HIV-infected
patients with pneumonia from the ED likely can
mirror practice for patients without an HIV in-
fection, although there are no evidence-based
guidelines on this topic. However, patients with
good social support who are followed closely by a
primary care provider and known to be compliant
with treatment are likely to be good candidates for
outpatient treatment.30
Chronic obstructive pulmonary disease (COPD)
is an increasing concern in HIV patients. Higher
rates of smoking in HIV-infected patients, lung in-
jury from previous OIs, and drug effects are all risk
factors for the development of COPD.31 Treatment
for COPD is the same as for noninfected patients.
Some data suggest that chronic HIV infection itself
may also be an independent risk factor for the
disease.32 The higher risk could be related to the
chronic systemic inflammatory response present
in longstanding infection. This inflammatory state
is also associated with hypercoagulability, leading
to higher rates of venous thromboembolism and
pulmonary embolism in this population.33 The Pul-
monary Embolism Rule-out Criteria (PERC) did not
report HIV status on the participants of the study, so
it is difficult to conclude whether these criteria can
be applied to HIV-infected individuals.
Emergency clinicians should have a high index
of suspicion for concomitant conditions in the
context of a patient’s CD4 count and be prepared
to evaluate patients with laboratory and radiologic
studies, as appropriate. Imaging with chest x-ray
should be considered in all patients with HIV and
pulmonary complaints.
Renal Disease
Renal disease in HIV patients can be caused both
by the HIV infection itself as well as the nephrotox-
icity of HAART. Patients present with acute kidney
injury similar to non–HIV-infected patients, and
their treatment is the same. Nephrotoxic medica-
tions should be withheld temporarily while the
patient is resuscitated.
7 Mobile app access: www.ebmedicine.net/app
 Clinical
ClinicalPathway
PathwayFor
ForEmergency Department
Management Management
Of Weakness Of Multiple
In HIV-Infected Patients
Shocks

HIV-infected patient presents with weakness

Rapidly assess for possible stroke syndrome. Perform a comprehensive physical and
neurologic examination, focusing on:
• Focal vs generalized findings
• Upper vs lower extremity asymmetry
• Cranial nerves
YES • Muscle tone and strength
• Upper and lower motor neuron findings

Is the weakness focal?

NO

Consider CNS causes Weakness is associated Weakness is Weakness is

Patient is on HAART
of unilateral weakness: with upper motor associated with generalized
• Stroke neuron findings lower motor neuron
• Tumor findings (reflexes,
• Spinal cord lesion fasciculations)

If the CD4 count is

< 200 cells/mm3:
Consider: Consider: Consider: Consider medication-
• Toxoplasmosis
• Spinal cord lesion • Guillain-Barré • Electrolyte specific effects:
• CNS lymphoma
• Spinal epidural syndrome abnormalities • Renal impairment
• Abscess
abscess • Cauda equina • Sepsis • Lactic acidosis
• Tuberculosis
• Radiculopathy • Hypothyroid • Anemia/bone marrow
(Class III)
If the CD4 count is • Adrenal insufficiency suppression
< 200 cells/mm3: If the CD4 count is • Acute coronary • Dehydration from
• HIV myelopathy < 200 cells/mm3: syndromes diarrhea
(Class III) • HIV polyneuropathy • Dehydration (Class III)
(Class III) • Myasthenia gravis
• Botulism
(Class III)

Abbreviations: CD4, CD4 T lymphocyte; CNS, central nervous system; CT, computed tomography; HAART, highly active antiretroviral therapy; HIV,
human immunodeficiency virus; MRI, magnetic resonance imaging.

Class Of Evidence Definitions

Each action in the clinical pathways section of Emergency Medicine Practice receives a score based on the following definitions.
Class I Class II Class III Indeterminate
• Always acceptable, safe • Safe, acceptable • May be acceptable • Continuing area of research
• Definitely useful • Probably useful • Possibly useful • No recommendations until further
• Proven in both efficacy and effectiveness • Considered optional or alternative treat- research
Level of Evidence: ments
Level of Evidence: • Generally higher levels of evidence Level of Evidence:
• One or more large prospective studies • Nonrandomized or retrospective studies: Level of Evidence: • Evidence not available
are present (with rare exceptions) historic, cohort, or case control studies • Generally lower or intermediate levels • Higher studies in progress
• High-quality meta-analyses • Less robust randomized controlled trials of evidence • Results inconsistent, contradictory
• Study results consistently positive and • Results consistently positive • Case series, animal studies, • Results not compelling
compelling consensus panels
• Occasionally positive results

This clinical pathway is intended to supplement, rather than substitute for, professional judgment and may be changed depending upon a patient’s individual
needs. Failure to comply with this pathway does not represent a breach of the standard of care.
Copyright © 2016 EB Medicine. 1-800-249-5770. No part of this publication may be reproduced in any format without written consent of EB Medicine.

Copyright © 2016 EB Medicine. All rights reserved. 8 Reprints: www.ebmedicine.net/empissues

 Nephrolithiasis and urolithiasis are common
side effects of PIs, particularly indinavir (although
few HIV-infected patients take this medication and,
instead, take one of the newer PIs). PIs have poor
solubility and significant urinary excretion that
leads to stone formation. Urinalysis will most likely
demonstrate hematuria; however, stones comprised
of indinavir deposits are typically radiolucent and
may be missed by standard radiologic imaging.
Therefore, secondary signs of obstruction, such as
hydroureter and perinephric stranding, may be
the only findings on imaging. Discussion with the
patient’s HIV provider regarding the continuation
or cessation of indinavir is advised. Treatment of
nephrolithiasis and urolithiasis are the same as for
the non–HIV-infected patient.
Neurologic Disease
Evaluation of the HIV-infected patient with a
neurologic complaint should be guided by the CD4
count. Patients with HIV infection, even if it is well-
controlled, have a slightly higher risk of cerebrovas-
cular disease due to the chronic inflammatory state,
accelerated atherosclerosis, and metabolic effects of
medications. The evaluation of patients with fo-
cal neurologic deficits should follow typical stroke
algorithms.
Rates of central nervous system OIs, such as
cryptococcal meningitis, toxoplasmosis, progressive
multifocal leukoencephalopathy, and Cytomegalovi-
rus have decreased significantly with treatment ad-
herence. However, if a patient with a low CD4 count
is identified, imaging and, possibly, lumbar puncture
aimed at the identification of OI is indicated. CT
of the head may require contrast in order to bet-
ter identify infectious processes or central nervous
system malignancy, such as lymphoma. MRI pro-
vides identification of smaller lesions and evaluates
leptomeningeal enhancement better than CT.
HIV myelopathy may develop at the end stages
of untreated disease. Patients develop lower extrem-
ity weakness associated with sensory abnormalities,
imbalance, and incontinence. Patients are hyperre-
flexic, with normal imaging studies and abnormali-
ties on electrophysiologic testing.
The prevalence of HIV-associated dementia has
also decreased since the introduction of HAART.34
Rates of milder neurocognitive disorders also ap-
pear to decrease with longer periods of undetect-
able virus.35,36
Gastrointestinal And Hepatobiliary Disease
Gastrointestinal symptoms, especially diarrhea, are
some of the most common presentations of HIV-
infected patients in the ED. In a large cohort study,
40% of HIV infected adults on HAART reported at
least 1 episode of diarrhea in the past month, with
3% reporting severe diarrhea (defined as > 6 stools
February 2016 • www.ebmedicine.net
per day).37 Etiologies include infectious diseases,
malignancies, and medication-induced diarrhea.
The pathogenesis of gastrointestinal symptoms
depends on the degree of immunocompromise.
Common pathogens that cause diarrhea in healthy
individuals will also do so in HIV-infected patients
on HAART. In the pre-HAART era, Clostridium
difficile was the most common pathogen isolated in
HIV-infected patients with diarrhea; however, with
successful treatment with HAART, the frequency
of hospitalizations and diagnosis of AIDS are both
decreased. Therefore, C difficile may not be the most
frequent infection, though it is more common in
HIV-infected individuals than in non–HIV-infected
individuals.38
As the CD4 count drops, the patient is at risk for
OIs such as Cryptococcus, Cytomegalovirus, microspo-
ridiosis, and Mycobacterium avium complex. In many
cases, initiation of HAART to restore the gastroin-
testinal immune system will help eradicate these
infections. Stool laboratory studies are guided based
on the patient’s stage of disease.
Hepatobiliary complaints are also common
in HIV-infected patients and may be caused by a
variety of etiologies from infectious to infiltrative
to medication-related problems. Co-infection with
hepatitis C virus affects 30% to 80% of HIV patients
and chronic hepatitis B virus affects 5% to 10% of
patients.39,40 Co-infection with either virus increases
a patient's risk of developing chronic hepatitis 2 to 3
times compared to non–HIV-infected patients with
hepatitis B virus or hepatitis C virus. Nearly all of
the HAART medications have potential hepatotoxic-
ity that can be worsened by co-infection with hepati-
tis B virus or hepatitis C virus.41
Patients with hepatobiliary complaints should
be asked about their medication regimens and any
co-infections with hepatitis B virus or hepatitis C
virus. Laboratory evaluations should include trans-
aminases, bilirubin, and lipase.
Hematologic Disease
Cytopenias of all cell lines are common in HIV-
infected patients. Patients with an uncontrolled
HIV infection may develop pancytopenia, as bone
marrow production is suppressed. Anemia may be
caused by a primary HIV infection or as a result of
medication use. Medication-induced anemia is often
macrocytic, although in the ED evaluation, this is a
diagnosis of exclusion.
The rate of HIV-associated thrombocytopenia
increases with decreasing CD4 count. Initiation of
HAART, particularly AZT/ZDV, is the mainstay of
treatment. These medications are rarely initiated in
the ED, and patients with severe or symptomatic
thrombocytopenia should be evaluated in consulta-
tion with the appropriate specialists.
HIV-infected patients also have higher rates
9 Mobile app access: www.ebmedicine.net/app
of thromboembolic disease, with a large prospec-
tive study estimating the rate to be 2.6 per 1000
patient-years.42 The chronic inflammatory state of
HIV infection appears to be a risk factor for throm-
boembolic disease. In HIV-infected patients without
well-controlled disease, factors associated with
thrombotic complications include lower CD4 count,
higher viral load, presence of OI, malignancy, and
indwelling central venous catheters.43 Thrombotic
thrombocytopenic purpura occurs in HIV-infected
patients, although its prevalence has decreased in
the HAART era. Patients with hemolytic anemia and
thrombocytopenia should be evaluated for throm-
botic thrombocytopenic purpura.44
Endocrine Disease
HAART is associated with dyslipidemia and truncal
obesity. This pattern of central fat accumulation and
peripheral fat loss has been termed HIV-associated
lipodystrophy syndrome. Prevalence of lipodystrophy
Risk Management Pitfalls For Managing HIV-Infected Patients
In The Emergency Department (Continued on page 11)
1. “I know he had long-standing HIV, but he was
only 42 years old, and I thought that was too
young to have acute coronary syndromes.”
HIV and HAART are synergistic in causing
cardiovascular disease. A chronic inflammatory
state caused by HIV itself, as well as side
effects of HAART, may act together to cause
cardiovascular disease. If the patient has been
HIV-infected for an extended period of time,
acute coronary syndromes should be in the
differential.
2. “This patient presented with fever, generalized
lymphadenopathy, sore throat, and a macular
rash. He is concerned about HIV infection, but
his rapid HIV test is negative.”
This patient has symptoms consistent with acute
seroconversion illness. Rapid testing technology
may miss early infection, and therefore a viral
load must be sent in order to properly identify
these patients.
3. “My patient presented with generalized weak-
ness but recently had a high CD4 count.”
Remember that common causes of weakness in
the non–HIV-infected patient are also common
in the HIV-infected patient. For this patient,
think beyond opportunistic infections and
consider sepsis and metabolic etiologies (such as
hypoglycemia) and derangements in potassium
and calcium. In the winter months, also consider
carbon monoxide poisoning.
Copyright © 2016 EB Medicine. All rights reserved. 10
ranges from 10% to 80%, depending on the defini-
tion of lipodystrophy.45 The most important risk
factor for development of this condition appears to
be NRTI use.46
Prior to widespread use of HAART, endocrine
complications of OIs were much more prevalent.
These complications included glandular infection
and infiltration of the pituitary, adrenal, and, rarely,
thyroid glands. Although these conditions are
much less common now because of HAART, they
should still be considered, especially in patients not
on HAART or patients with AIDS. Glucocorticoid
deficiency can result from adrenal involvement, and
while it is usually subclinical, it should be consid-
ered in patients with AIDS and hypotension or criti-
cal illness. Treatment for these patients is the same as
for non–HIV-infected patients.
Patients on HAART are at risk for developing
thyrotoxicosis in association with immune recon-
stitution inflammatory syndrome due to autoim-
4. “My patient has a history of migraines; I as-
sumed this headache was a migraine as well.”
Emergency clinicians must be careful not to
anchor on prior headache diagnoses. The
primary goal is to rule out dangerous causes
of headaches, even in patients who have a
history of benign headaches. Patients with
migraines or tension headaches can still suffer
from meningitis, subarachnoid hemorrhage, or
other causes of series or secondary headaches.
A careful HIV history, with particular attention
to the CD4 count, and thorough neurological
examination is critical in HIV-infected patients
presenting with headache. This process will
often help differentiate patients who will require
imaging and further testing.
5. “My patient complained of diarrhea for the
past 2 weeks since starting HAART, and the
symptoms were interfering with her ability to
work. I thought it would be OK to temporar-
ily stop her medications until her primary care
provider could adjust them.”
Inconsistent compliance with HAART can cause
viral resistance to the medications. Therefore,
there are very few scenarios in which a patient
should stop HAART treatment. Stevens-Johnson
syndrome and nevirapine-associated hepatic
failure are indications to stop HAART. The
patient’s primary care provider or an HIV
medicine consultant should be involved in all
decisions to terminate HAART.
Reprints: www.ebmedicine.net/empissues
mune activation against the thyroid. Patients
generally present months to years after starting
HAART with symptoms of Grave disease, weight
loss, and tachycardia.47
Disorders of glucose metabolism are associated
with the use of HAART, particularly PIs. Addition-
ally, the disease itself is associated with an increased
incidence of diabetes as a result of chronic inflamma-
tion leading to insulin resistance.48
Musculoskeletal Disease
Patients with longstanding HIV infection who are on
treatment have lower bone mineral density when com-
pared with noninfected individuals of similar age.49
Therefore, HIV-infected patients are at increased risk
of fracture. HIV itself, as well as antiretroviral medica-
tions, are implicated in higher rates of avascular ne-
crosis. Benign musculoskeletal and joint complaints of
pain are common in the HIV-infected patient, and the
emergency clinician must differentiate between these
Risk Management Pitfalls For Managing HIV-Infected Patients
In The Emergency Department (Continued from page 10)
6. “A patient with a history of HIV infection and
COPD presented with shortness of breath and
mild pleuritic chest pain. He said that the pain
was not characteristic of his COPD exacerba-
tions. Oxygen saturation was normal and his
lungs were clear to auscultation.”
Consider pulmonary embolism in a patient
like this. HIV infection causes a chronic
inflammatory state, which is associated with
increased risk of venous thromboembolism.
7. “The patient frequently had loose stools, so I
thought his diarrhea was the same old thing.”
Diarrhea is a frequent complaint in HIV-infected
patients and can often be caused by medications.
However, dangerous etiologies occur frequently,
as well. It is important to question patients about
changes in bowel movements, recent travel history,
recent antibiotic use, and previous history of
gastrointestinal infections, and to assess for infectious
etiologies before blaming a medication side effect.
8. “There was no history of OI and he just started
HAART. I never thought he could have TB.”
Initiation of HAART treatment places patients at
risk of unmasking previously unrecognized OI.
Although it may seem counterintuitive, starting
treatment can actually be dangerous in patients
with very low CD4 counts. When these patients
present to the ED, OIs and medication side
effects should both be considered as etiologies of
their complaints.
February 2016 • www.ebmedicine.net
and more significant pathology. Infectious complica-
tions (such as septic arthritis) are less common with
improved control of the disease. As the CD4 count
drops, septic arthritis, osteomyelitis, and discitis must
be considered with appropriate evaluation, including
laboratory testing and imaging studies.50
Psychiatric Disease
Neuropsychiatric illness is prevalent and multifac-
torial in HIV-infected individuals. Direct effects of
the virus, underlying mental illness, and the social
implications of an HIV diagnosis all contribute to
psychiatric illness. Medication effects, notably efavi-
renz, also contribute. Depression is one of the most
common diagnoses in HIV-infected patients and is
associated with decreased medication compliance.23
Demoralization syndrome is similar to depres-
sion in that patients experience a sense of hope-
lessness or sadness. However, it is different from
depression because it is not associated with anhe-
9. “The patient complained of feeling 'off bal-
ance.' She had mild ataxia, but the CT scan was
normal. I never expected a cerebellar lesion.”
Remember the limitations of nonenhanced
CT scans. Patients with poorly controlled HIV
are at higher risk for central nervous system
infections, including toxoplasmosis, which may
be missed on this type of CT scan. Patients with
a concerning history or physical examination
should receive additional testing when a
nonenhanced CT scan is negative.
10. “He recently discontinued his tenofovir. The
liver function tests were high. I still don't un-
derstand what happened.”
Tenofovir, emtricitabine, and lamivudine are
also active against hepatitis B virus. Termination
of these agents in patients with co-infection
can precipitate a severe and sometimes fatal
hepatitis flare that must be included in the
differential diagnosis of this patient. Along
with evaluating other etiologies of hepatitis,
consultation with an HIV medicine specialist
about reinitiating these medications is
suggested.
11 Mobile app access: www.ebmedicine.net/app
donia. Demoralization is common in patients with
HIV and may be related to the social implications
of being diagnosed with HIV. Unlike depression,
demoralization does not respond to antidepressants
and requires further evaluation and treatment by a
psychiatrist.
Mania is also a recognized complication of
HIV disease. Patients presenting to the ED with
symptoms consistent with this should be evaluated
for organic etiologies of their symptoms and then
referred to psychiatric services. Patients present-
ing to the ED with symptoms concerning for any
mental illness should be questioned about suicidal
and homicidal ideation and admitted if either are
present; otherwise, they should receive prompt
outpatient follow-up.
Dermatologic Disease
Dermatologic complaints are common in HIV-
infected patients. HAART is associated with a high
rate of drug-related skin reactions, which can lead to
medication noncompliance.51 Dermatologic hyper-
sensitivity and photosensitivity are both common
with HAART.
Although treatment with HAART seems to be
associated with a lower risk of infectious derma-
tologic conditions, rates of these infections remain
high.52 Folliculitis is likely the most common of
these, with Staphylococcus aureus being the most
common pathogen, particularly the methicillin-resis-
tant strain. Other common infectious dermatologic
complaints, including herpes zoster, human papil-
lomavirus-associated warts, seborrheic dermatitis,
and molluscum contagiosum, are more common in
HIV-infected patients, with treatment considerations
being the same as in non–HIV-infected patients.
Special Circumstances
HIV-infected patients with sexual partners, or
patients with a sexual partner of unknown status,
may present to the ED after sexual encounters
during which barrier methods of protection are
compromised, ie, condom breakage or lack of
condom usage. In these instances, the emergency
clinician must counsel the patient regarding PEP
and potentially initiate treatment. The ED is also a
frequent portal of entry for healthcare workers and
others with potential exposures to HIV through
percutaneous or mucous membrane exposure. The
risk of HIV transmission depends on both the type
of exposure and stage of illness in the source of the
exposure (if known).
PEP is most effective when administered soon
after the exposure, ideally within 2 hours. The
United States Centers for Disease Control and
Prevention recommend that PEP be initiated as
soon as possible, preferably within 72 hours of the
Copyright © 2016 EB Medicine. All rights reserved. 12
exposure.53 Individual states may have different
guidelines, and emergency clinicians should be
aware of local regulations. The exposed patient
should have baseline HIV testing performed. A
multidrug regimen is recommended, extrapolating
the success of using combination therapy in the
treatment of HIV. Randomized data on the success
of PEP are not available; however, rates of sero-
conversion remain low when therapy is initiated
early with full compliance.54
Summary
When evaluating the HIV-infected ED patient, the
first step is an assessment of the status of disease.
The differential diagnosis of a patient’s symptoms
will change significantly based on the CD4 count
and viral load. Patients with low CD4 counts (< 200
cells/mm3) must have a complete history, review
of systems, and physical examination in order to
identify any OIs. When the CD4 count is unknown,
the absolute lymphocyte count might be a helpful
surrogate. HIV-infected patients with well-controlled
disease taking medications are living longer and are
now experiencing side effects possibly due to the
chronic inflammatory state of HIV and adverse drug
reactions. It is critical to understand the organ-specif-
ic complications of chronic HIV infection and more
common adverse medication effects. In particular,
patients with longstanding HIV infection are likely
at higher risk of coronary artery disease, thrombo-
embolic disease, and COPD. Commonly used HIV
medications carry the risk of multiple drug interac-
tions, and emergency clinicians must cross-check
ED therapy and new prescriptions with the patient’s
home medication regimen.
Key Points
• A thorough history should include the patient’s
most recent CD4 count, CD4 nadir, viral load,
and a list of the patient’s medications.
• HAART (especially PIs) increase triglycerides
and LDL (low-density lipoprotein) and lower
HDL (high-density lipoprotein) levels, causing
higher risk of coronary artery disease.
• Systemic inflammatory response associated with
chronic HIV leads to coronary artery disease, hy-
percoagulability, and venous thromboembolism.
• Ritonavir increases bioavailability of cortico-
steroids and can lead to iatrogenic Cushing
syndrome.
• Nonenhanced CT scans can miss nephrolithiasis
caused by radiolucent indinavir stones.
• Laboratory-based fourth-generation rapid
HIV tests have sensitivities > 90%, even in the
acute phase.
• HIV-infected patients with low CD4 counts are
Reprints: www.ebmedicine.net/empissues
 at risk for several central nervous system infec-
tions and diseases, such as progressive multifo-
cal leukoencephalopathy. Maintain a low thresh-
old for nonenhanced CT scans of the brain.
• Although diarrhea is very common in HIV-in-
fected patients and may have a benign etiology,
C difficile is also very common, so dangerous
etiologies of diarrhea should be excluded.
• Cytopenias of all cell lines are common in HIV-
infected patients.
• Demoralization syndrome presents similarly to
depression but is not improved by antidepres-
sants. Ask patients with psychiatric complaints
about suicidal and homicidal ideation.
• PEP is most effective if it is administered as close
to the time of exposure as possible. It is not rec-
ommended after 72 hours postexposure.
Case Conclusions
After reviewing the CT scan for the 28-year-old man with
flank pain and no identifiable stone, you decided to treat
him presumptively. You remembered that in patients tak-
ing indinavir, CT scans may not demonstrate the stone
and may show only secondary signs. The patient had
ongoing pain and urology was consulted. He was taken to
the operating room for ureteral stent in the context of an
obstructing radiolucent stone.
The 42-year-old woman’s laboratory test results
were notable for a leukocytosis of 14,000 cells/mm3. On
further questioning, she said that, although she was on
HAART and Pneumocystis pneumonia prophylaxis with
trimethoprim-sulfamethoxazole, she had not been able to
see a physician in over a year because of insurance prob-
lems. She did not remember the last time she had her CD4
count or viral load checked. You decided that this patient
was at high risk for C difficile infection. You started
metronidazole and admitted her to the hospital.
Upon speaking with the third patient, you realized
that she was most likely not responding to antidepressants
because she suffered from demoralization. She reported
that she had not been taking her HAART consistently
because, “What’s the point?” While she did not require
emergent psychiatric evaluation, you conferred with her
and her family members, and they agreed that she would
follow up with her psychiatrist to discuss her demoraliza-
tion and to pursue therapy. You reiterated the importance
of HAART compliance and counseled her that therapy
and proper treatment for demoralization may improve her
mood and her compliance with treatment.
Acknowledgement
The authors wish to thank Jennifer L. Galjour, MD,
MPH, Icahn School of Medicine at Mount Sinai, New
York, NY, for her assistance with this issue.
February 2016 • www.ebmedicine.net
References
Evidence-based medicine requires a critical ap-
praisal of the literature based upon study methodol-
ogy and number of subjects. Not all references are
equally robust. The findings of a large, prospective,
random­ized, and blinded trial should carry more
weight than a case report.
To help the reader judge the strength of each
reference, pertinent information about the study are
included in bold type following the ref­erence, where
available. In addition, the most informative referenc-
es cited in this paper, as determined by the authors,
are noted by an asterisk (*) next to the number of the
reference.
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32. Crothers K, Butt AA, Gibert CL, et al. Increased COPD
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49. Takhar SS, Hendey GW. Orthopedic illnesses in patients with 3. The most common cause of community-ac-
HIV. Emerg Med Clin North Am. 2010;28(2):335-342. (Review) quired pneumonia in HIV patients on HAART
50. Marquez J, Restrepo CS, Candia L, et al. Human immu-
nodeficiency virus-associated rheumatic disorders in the
is:
HAART era. J Rheumatol. 2004;31(4):741-746. (Prospective; 75 a. Pneumocystis jiroveci
patients) b. Streptococcus pneumoniae
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Dis. 2004;38(4):579-584. (Cross-sectional; 800 patients) a. Protease inhibitors
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July 30, 2015. (CDC website)
c. Integrase inhibitors
54. Thomas R, Galanakis C, Vezina S, et al. Adherence to post- d. Nephrolithiasis is not a known complication
exposure prophylaxis (PEP) and incidence of HIV serocon- of HAART
version in a major North American cohort. PLoS ONE. 2015;
11;10(11):e0142534. (Prospective; 3547 patients) 5. Which of the following is associated with
increased risk of cerebrovascular accidents in
CME Questions patients with HIV?
a. Progressive multifocal leukoencephalopathy
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includes 4 AMA PRA Category 1 CreditsTM, 4 ACEP 6. Which of the following is NOT a common eti-
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7. Which of the following statements about hepa-

tobiliary disease in HIV infection is FALSE?
a. Co-infection with either hepatitis B or
hepatitis C increases a person’s risk of
chronic hepatitis by 2 to 3 times compared to
1. The United States Department of Health and non–HIV-infected patients.
Human Services recommends treatment with b. HIV-infected patients with hepatobiliary
HAART for which of the following groups of complaints in the ED should receive
HIV-infected patients? laboratory testing with transaminases,
a. Patients with CD4 count < 350 cells/mm3 bilirubin, and lipase.
b. Patients with CD4 count < 500 cells/mm3 c. Hepatobiliary disease in HIV patients only
without opportunistic infection occurs in the presence of co-infection with
c. Patients with CD4 count > 500 cells/mm3 hepatitis B or hepatitis C.
with previous opportunistic infection d. Co-infection with hepatitis C affects up to
d. All of the above 80% of HIV patients, depending on risk
factors.
2. Which of the following factors is NOT impli-
cated in the increased risk of cardiovascular 8. Anemia is common in patients with HIV on
disease seen in patients with HIV? HAART. This is likely secondary to which of
a. History of smoking the following?
b. A systemic inflammatory response a. Medication side effect
associated with HIV infection b. Hemolysis
c. HAART c. A response to thrombocytopenia
d. Opportunistic infection d. Disseminated intravascular coagulation

February 2016 • www.ebmedicine.net 15 Mobile app access: www.ebmedicine.net/app

9. Factors associated with thromboembolic Physician CME Information
disease include all of the following EX- Date of Original Release: February 1, 2016. Date of most recent review: January 10, 2016.
Termination date: February 1, 2019.
CEPT:
Accreditation: EB Medicine is accredited by the Accreditation Council for Continuing Medical
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of his HIV-infected partner broke during for one year from this date. Each issue is approved for 4 Prescribed credits. Credit may be
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sexual intercourse. Which of the follow- commensurate with the extent of their participation in the activity.
ing is true? AOA Accreditation: Emergency Medicine Practice is eligible for up to 48 American
a. Initiation of treatment with Osteopathic Association Category 2-A or 2-B credit hours per year.
Needs Assessment: The need for this educational activity was determined by a survey
antiretroviral medication is of medical staff, including the editorial board of this publication; review of morbidity and
contraindicated after 36 hours mortality data from the CDC, AHA, NCHS, and ACEP; and evaluation of prior activities for
emergency physicians.
postexposure.
Target Audience: This enduring material is designed for emergency medicine physicians,
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infection. treat the most critical presentations; and (3) describe the most common medicolegal pitfalls
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exposure. investigational information about pharmaceutical products that is outside Food and Drug
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