The spectrum of disease caused by HIV infection varies greatly.
Many patients with asymptomatic infection come to the ED because
of complaints unrelated to HIV disease. Symptomatic patients may
have involvement of virtually any organ system, commonly with multiple
interrelated problems. The protean manifestations of HIV and the
complex array of related opportunistic infections can make ED evaluation
and diagnosis of HIV-positive patients difficult.
Evaluation of HIV-infected patients should be carried out with
the same priority-based logical approach used for all ED patients,
with attention to concerns particular to this population.
Attempts to develop specialized triage guidelines for HIV-positive
patients have so far been unsuccessful.20 Patients
with unstable vital signs require attention to the airway, breathing,
and circulation, and rapid stabilization. Always use universal
precautions (in some hospitals termed standard
precautions). Focus the history taking and
physical examination on identifying the clinical stage of disease
in order to direct attention to the most likely complications. Obtain
a thorough report of past and current medications and previous infections
and ask about the patient’s ability to perform activities
of daily living. Physical findings that might assist with staging
include the presence of thrush, evidence of temporal wasting, and
the presence of dementia.
Diagnosis and treatment are directed toward recognition of organ
system involvement, assessment of the severity of disease, and institution
of symptomatic and specific therapy. An overview of the more common HIV-related
presentations and treatment is provided in the following sections.
For the most up-to-date information, as well as more details on drug
dosing, the reader is referred to the CDC Web site (http://www.cdc.gov/hiv/dhap.htm)
or the Johns Hopkins University School of Medicine annually updated
guide to care of the HIV-positive patient, which provides an excellent
clinical resource tool.21
Symptoms and Febrile Illnesses—Initial Stabilization
Systemic symptoms such as fever, weight loss, and malaise are
common in HIV-infected patients and account for the majority of
HIV-related ED presentations.22 In the ED, identify
or exclude systemic infection and any acute life-threatening manifestations
of malignancy. Appropriate laboratory investigation may include
electrolyte determinations, complete blood count, blood cultures
(for aerobic, anaerobic, and fungal organisms), urinalysis and urine
culture, liver function tests, chest radiograph, and serologic testing
for syphilis, cryptococcosis, toxoplasmosis, CMV infection, and
coccidioidomycosis. Lumbar puncture (LP) may be considered if there
are neurologic signs or symptoms or unexplained fever.
Patients with later-stage HIV/AIDS may not manifest
the typical signs and laboratory findings associated with systemic
infection. Clinical impression therefore is critical in determining
clinical evaluation and appropriate disposition. Ill-appearing patients
should receive fluid resuscitation, empiric antibiotics in the ED,
and admission for further evaluation and management. Outpatient
evaluation and treatment are indicated only when all of the following
conditions are met: the source of the fever does not dictate admission,
appropriate laboratory studies have been initiated, the patient is
able to function adequately at home (e.g., can maintain sufficient
oral intake), and timely medical follow-up can be arranged.
HIV Stage and
Causes of Fever
In HIV-positive patients without obvious localizing signs or
symptoms, sources of fever vary by stage of disease. Patients with
CD4+ T-cell counts of >500 cells/mm3 generally
have causes of fever similar to those in nonimmunocompromised patients,
whereas those with CD4+ T-cell counts between 200 and 500
cells/mm3 are most likely
to have early bacterial respiratory infections.23 For
patients with CD4+ T-cell counts of <200 cells/mm3,
the most common causes of fever without obvious localizing findings
are early Pneumocystis carinii (P. jiroveci)
pneumonia (PCP); central line infection; infection with MAC, M.
tuberculosis, or CMV; drug fever; and sinusitis (see Chapter 239, Epistaxis, Nasal Fractures, and Rhinosinusitis).
Less common causes of fever include endocarditis, lymphoma, and
infection with Histoplasma capsulatum or Cryptococcus
neoformans. Fever caused by HIV infection alone tends to occur
in the afternoon or evening and generally is responsive to antipyretics.
Disseminated MAC infection occurs
predominantly in patients with CD4+ T-cell counts of ≤100
cells/mm3. Persistent fever
and night sweats are typical. Associated symptoms include weight
loss, diarrhea, malaise, and anorexia. Dissemination to the bone
marrow, liver, and spleen results in anemia and elevated alkaline
phosphatase levels. Diagnosis may be made by acid-fast stain of
stool or other body fluids or by blood culture. Cultures using the
lysis-centrifugation method are more sensitive for MAC (and histoplasmosis)
and should be ordered for patients with late-stage disease and fever
of unknown origin. Treatment for MAC reduces bacteremia and improves
symptoms (but does not eradicate disease). Treatment should be initiated
with clarithromycin combined with ethambutol and rifabutin (Table 149-2).
149-2 Treatment Recommendations for Common Human Immunodeficiency Virus–Related
Infections |Favorite Table|Download (.pdf)
149-2 Treatment Recommendations for Common Human Immunodeficiency Virus–Related
|Systemic||Mycobacterium avium-intracellulare||Clarithromycin, 500 milligrams PO twice a day|
|Ethambutol, 15 milligrams/kg PO once a day|
|Rifabutin, 300 milligrams/kg PO once a day|
|CMV infection||Ganciclovir, 5 milligrams/kg IV twice a day for 2
wk, then 5 milligrams/kg/d|
|Foscarnet, 90 milligrams/kg every 12 h for 3
wk, then 90 milligrams/kg once a day|
|Pulmonary||Pneumocystis jiroveci (P. carinii )
pneumonia||Trimethoprim/sulfamethoxazole dose using 15–20
milligrams of trimethoprim component per kilogram per day PO or
IV in divided doses three times a day for 3
|If partial pressure of arterial oxygen is
<70 mm Hg or alveolar-arterial gradient is >35 mm Hg, then
|Prednisone, 40 milligrams twice a day for 5 d, then 40
milligrams once a day for 5 d, then 20
milligrams once a day for 11 d|
|Pentamidine, 4 milligrams/kg/d IV or IM for 3
|Mycobacterium tuberculosis infection*||Isoniazid, 5 milligrams/kg PO once a day|
|Rifampin, 10 milligrams/kg PO once a day or rifabutin
5 milligrams/kg PO once a day |
|Pyrazinamide, 15–30 milligrams/kg PO once
a day |
|Ethambutol, 15–20 milligrams/kg PO once
a day |
|Central nervous||Toxoplasmosis†||Pyrimethamine, 200-milligram loading dose PO followed by
50–75 milligrams PO once a day for 6–8
|Sulfadiazine, 1 to 1.5 grams PO every 6 h for 6–8
|Folinic acid, 10 milligrams/d PO for 6–8
|plus or minus|
|Leucovorin, 10–25 milligrams once a day|
|Cryptococcosis‡||Amphotericin B, 0.7 milligram/kg IV once a day for 2
|Flucytosine, 25 milligrams/kg IV four times a day for 2
|Fluconazole, 400 milligrams/d PO for 8–10
|Ophthalmologic||CMV infection#||Ganciclovir implant|
|Ganciclovir, 1.0–1.5 grams PO three times a day |
|Ganciclovir, 5 milligrams/kg IV twice a day for 2–3
|GI||Candidiasis (thrush–limited to mouth)||Clotrimazole, 10-milligram troches five times
|Nystatin, 500,000 units five times a day,
|Esophagitis (primarily Candida)||Fluconazole, 100–400 milligrams/d PO|
|Salmonellosis†||Ciprofloxacin, 500 milligrams PO twice a day for 2–4
|Cryptosporidiosis||No known effective cure; best results with highly active
|Cutaneous||Herpes simplex||Acyclovir, 200 milligrams PO five times a day
for 7 d|
|Famciclovir, 125 milligrams PO twice a day for 7
|Valacyclovir, 1 gram PO twice a day for 7 d|
|or for severe disease|
|Acyclovir, 5–10 milligrams/kg IV every
8 h for 7 d |
|Herpes zoster||Acyclovir, 800 milligrams PO five times a
day for 7–10 d|
|Famciclovir, 500 milligrams PO three times a day for 7–10
|Valacyclovir, 1 gram PO three times a day for 7–10
|or for ocular or disseminated disease|
|Acyclovir, 5–10 milligrams/kg PO every
8 h for 5–7 d|
|Candida or Trichophyton infection||Topical clotrimazole two or three times a day for 3 wk|
|Topical miconazole two or three times a day for 3 wk|
|Topical ketoconazole two or three times a day for 3 wk|
With increased use of HAART, a more focal and invasive form of
MAC infection has emerged called immune reconstitution
illness to MAC.24 Typical presentation
is lymphadenitis, with symptoms commonly starting weeks to months
after beginning HAART. Current treatment guidelines advise continuing
antiretroviral therapy and starting antimicrobials. Steroids may
be beneficial. Immune reconstitution illness also has been seen
with a group of other infections, including tuberculosis (TB), CMV
infection, cryptococcosis, hepatitis, herpes zoster, and progressive
multifocal leukoencephalopathy. Symptoms often resemble those of
the original infection and are due to inflammation.25
CMV is the most common cause of serious opportunistic
viral disease in HIV-infected patients. Disseminated disease commonly
involves the GI, pulmonary, and central nervous systems. The most
important manifestation is retinitis (see Cytomegalovirus
Retinitis below). Treatment is with foscarnet or ganciclovir.
Oral ganciclovir can be used for prophylaxis (Table
Fever in injection drug users always should raise
concern for infective endocarditis, which often has a nonspecific
presentation in the ED (see Chapter 294, Injection Drug Users, and Chapter 150, Infective Endocarditis).
Although previous studies have failed to identify reliable clinical
or laboratory predictors of infective endocarditis in febrile injection
drug users, molecular diagnostic assays such as polymerase chain reaction
testing may prove useful.26,27 Current standard
of care is to admit febrile injection drug users and await the results
of blood cultures and echocardiography. Admission is recommended
due to the significant morbidity and mortality associated with missed
endocarditis and the difficulties encountered with outpatient follow-up
in this population.
The most common noninfectious causes of fever in HIV patients are neoplasm
and drug fever. Non-Hodgkin lymphoma is the most frequently occurring
neoplasm and is characterized by high-grade, rapidly growing mass
lesions. New central nervous system (CNS) symptoms, particularly
a change in mental status in the presence of fever, should be evaluated
with neuroimaging. Definitive diagnosis requires biopsy. Radiotherapy
and chemotherapy are effective treatment regimens. Drug fever may
be secondary to injection drug abuse or adverse drug reactions (see
Drug Interactions and Adverse Effects in HIV-Infected Patients below).
CNS disease occurs in 90% of patients with AIDS, and
10% to 20% of HIV-infected patients present initially
with CNS symptoms. Neurologic disease is caused by a variety of
opportunistic infections and neoplasms, as well as by the direct
and indirect effects of HIV infection on the CNS. Common presenting
symptoms indicative of CNS pathology include seizures, altered mental
status, headache, meningismus, and focal neurologic deficits. The
most common causes of neurologic symptoms include AIDS dementia, Toxoplasma
gondii infection, and C. neoformans infection.
Since the widespread use of HAART, rates of CNS infection and malignancy
have declined significantly, whereas rates of AIDS dementia remain
ED evaluation should include a complete neurologic examination
and, when appropriate, CT and LP. In general, CT should precede
LP. Fever, meningismus, altered mental status, and headache are
independent predictors of space-occupying lesions.28,29
Although there are no uniform consensus guidelines on workup
of HIV-positive patients with headache, the following approach is
recommended.30 Neuroimaging and LP are indicated
for those in whom an alternative explanation is not found or for
those for whom there is a clear indication for further investigation
(e.g., patient report of “worst headache of my life”).
For those with CD4+ T-cell counts of <200 cells/mm3, a
more aggressive approach is advocated.29 Headache
in combination with altered mental status, seizures, or focal findings
requires emergent imaging. LP should be performed if imaging is
unrevealing. Isolated headaches that are protracted or have changed
in quality (even in the absence of other neurologic findings) also
should prompt immediate neuroimaging.28
Non–contrast-enhanced CT is an appropriate initial imaging
study in the ED in HIV-infected patients with neurologic deficits,
because the addition of contrast material has marginal value in
patients with completely normal non–contrast-enhanced CT
scans.29,31 In patients in whom clinical suspicion
of CNS pathology is high but the CT scan findings are equivocal
or negative, contrast-enhanced CT scanning or MRI should be arranged
in the ED. Specific CSF studies that may be of value include opening
and closing pressures, cell count, glucose level, protein level, Gram
staining, India ink staining, bacterial culture, viral culture,
fungal culture, toxoplasmosis and cryptococcosis antigen assays,
and coccidioidomycosis titer. If possible, excess CSF should be
held for additional testing in the event that the diagnosis remains
unclear. Even if the ED evaluation is unrevealing, all patients
with new or changed neurologic signs or symptoms should be admitted
to the hospital.
AIDS dementia complex (also referred to as HIV encephalopathy or subacute
encephalitis) is a progressive disorder commonly heralded
by subtle impairment of recent memory and other cognitive deficits.
It occurs in 10% to 15% of HIV-positive patients,
although up to 30% of patients with CD4+ counts
of <100 cells/mm3 have the disorder.32 In
the early stages, AIDS dementia can be confused with depression,
anxiety disorders, or substance abuse. Later phases of the illness
are characterized by obvious changes in mental status as well as
aphasia and motor abnormalities. Patients with an established diagnosis
of AIDS dementia who develop progressive neurologic or psychologic
signs or symptoms warrant further evaluation for systemic or CNS
processes. A CT scan in patients with AIDS dementia typically shows
cortical atrophy and ventricular enlargement. AIDS dementia is associated
with elevated protein levels in the CSF in 50% to 70% of
Toxoplasmosis is the most common cause of focal encephalitis
in patients with AIDS. Symptoms may include headache, fever, focal
neurologic deficits, altered mental status, and seizures. Serologic
tests are not useful in making or excluding the diagnosis, because
antibodies to T. gondii are prevalent in the general
population. A finding of antibodies to T. gondii in
the CSF is helpful, although there is a high rate of false negative
results. On a non–contrast-enhanced CT scan, toxoplasmosis
typically appears as multiple subcortical lesions with a predilection
for the basal ganglia.
In general, only a non–contrast-enhanced CT scan is
indicated in the ED, with inpatient studies to further delineate
the lesion. When a contrast medium is used, toxoplasmosis lesions
are ring enhancing, with surrounding areas of edema. MRI is slightly
more sensitive than contrast-enhanced CT scan in detecting the extent
and number of lesions in toxoplasmosis. Other disorders in the differential
diagnosis of ring-enhancing lesions on contrast-enhanced CT include
lymphoma, fungal infection, and cerebral TB. In the ED, often it
is not possible to differentiate these causes based on initial imaging
studies, but general patterns in the appearance of lesions, based
on underlying pathology, have been described. Toxoplasmosis tends to
produce a greater number of lesions with a predilection for the
basal ganglia and corticomedullary regions, whereas lymphoma is
characterized more often by single lesions in the periventricular
white matter or corpus callosum. TB is distinguished by a characteristic
inflammatory appearance on CT, with a thick, isodense exudate filling
the basal cisterns.
Patients with suspected toxoplasmosis should be admitted and
treated with pyrimethamine and sulfadiazine, with folinic acid added
to reduce hematologic toxicity (Table 149-2).
Steroids (dexamethasone, 4 milligrams IV every 6 hours) are beneficial
for significant edema or mass effect.
Failure to improve with treatment suggests an alternative diagnosis,
the identification of which may require biopsy. For patients responsive
to toxoplasmosis therapy, chronic suppressive therapy with pyrimethamine,
sulfadiazine, and folinic acid is usually indicated after initial
treatment. Oral sulfamethoxazole-trimethoprim, one double-strength
(DS) tablet daily, is recommended for prophylaxis in patients with
positive toxoplasmosis serologic test results and CD4+ T-cell counts
of <100 cells/mm3.
Cryptococcal CNS infection can produce either focal cerebral
lesions or diffuse meningoencephalitis. The most common presenting
signs are fever and headache, followed by nausea, altered mentation,
and focal neurologic deficits. Presentation may be subtle, and meningismus
is uncommon. Neuroimaging studies usually produce normal findings.
Diagnosis relies on identifying organisms in CSF by cryptococcal
antigen testing (nearly 100% sensitive and specific), culture (95% to
100% sensitive), or staining with India ink (60% to
80% sensitive). Serum cryptococcal antigen testing is also
useful but has slightly lower sensitivity (approximately 95%).
Elevated intracranial pressure is associated with cryptococcal meningitis,
and an opening pressure of >25 cm H2O should prompt drainage
of fluid until pressure is <20 cm H2O or 50% of
opening pressure. Patients with CNS cryptococcosis need admission.
Treatment is IV amphotericin B with oral flucytosine for 14 days,
followed by fluconazole for 8 weeks to clear the CSF (Table
149-2). Sixty percent of patients may be expected to respond
to therapy, and side effects are frequent, most notably bone marrow
suppression. Lifelong maintenance therapy with fluconazole (200
milligrams/d) is indicated for patients but may be discontinued
if immune reconstitution is shown.
Other less common CNS infections that should be considered in
the presence of neurologic symptoms include bacterial meningitis,
histoplasmosis (usually disseminated), CMV infection, progressive
multifocal leukoencephalopathy, herpes simplex virus (HSV) infection,
neurosyphilis, and TB. Noninfectious CNS processes include CNS lymphoma
(typically manifested as a subacute neurologic deterioration over
several months with a single ring-enhancing lesion on CT), cerebrovascular
accidents, and metabolic encephalopathies.
The most common disorder of the peripheral nervous system is HIV neuropathy,
characterized by foot pain. Although HIV infection itself is the
most common culprit, HIV therapies also should be considered as
a possible cause, and changing treatment regimens may be helpful.
Pain-modifying agents such as nortriptyline can cause delirium in
patients with concurrent HIV dementia. Narcotic analgesia may be
needed in severe cases.
Common Ophthalmologic Complications
Seventy-five percent of patients with AIDS develop ocular complications.
Although a wide range of ophthalmic diseases occurs, recognition of
a few is most critical. The most common ophthalmic finding in patients
with AIDS is retinal microvasculopathy, which is characterized by retinal
cotton-wool spots identical in appearance to those seen in diabetes
or hypertension. Retinal microaneurysms are also seen, primarily
in the periphery. These lesions are believed to be incidental and
do not cause visual disturbances. The diagnostic dilemma is to distinguish
these findings from early CMV infection, and ophthalmologic consultation
CMV retinitis (Figure 149-1)
is the most frequent and serious ocular opportunistic infection
and is the leading cause of blindness in AIDS patients. In
the HAART era, the incidence of CMV infection has been reduced,
due in large part to immune reconstitution associated with the therapy.23 Signs
and symptoms of CMV retinitis are variable. Retinitis may be asymptomatic
early on but later causes changes in visual acuity, visual field
cuts, photophobia, and scotoma, and eye redness or eye pain may
develop. Findings on indirect ophthalmoscopy are characteristic,
with fluffy white perivascular lesions with areas of hemorrhage
within them. Intraocular ganciclovir implants are effective treatment,
in conjunction with oral ganciclovir; alternative first-line therapy
is ganciclovir without implants for 14 to 21 days (Table
149-2). Vision loss and blindness occur in all cases without
early detection and prompt treatment. Even with treatment, there
are frequent relapses and progression of disease, with 10% of
affected patients ultimately going blind.
Cytomegalovirus retinitis. “Pizza pie” or “cheese
and ketchup” appearance is demonstrated by hemorrhages
and the dirty white granular-appearing retinal necrosis adjacent
to major vessels. (Photograph contributed by Richard E. Wyszynski,
MD. Reproduced with permission from Knoop KJ, Stack LB,
Storrow AB, Thurman RJ: The Atlas of Emergency
Medicine, 3rd ed, © 2009 by McGraw-Hill
Inc., New York.)
Herpes zoster ophthalmicus usually presents with paresthesia
and discomfort in the distribution of cranial nerve V1 (ophthalmic
branch), followed by the appearance of the typical zoster skin rash.
Ocular complications include conjunctivitis, episcleritis, iritis, keratitis,
secondary glaucoma, and, rarely, retinitis.33 Early
recognition and treatment can prevent ocular damage. Preferred treatment
is described in Chapter 236, Eye Emergencies.
The most common causes of pulmonary abnormalities in HIV-infected patients
are community-acquired bacterial pneumonia, PCP, TB, CMV infection,
cryptococcosis, histoplasmosis, and neoplasms. The most common
cause of pneumonia in HIV-infected patients is Streptococcus
addition to history taking and physical examination, evaluation
of patients with pulmonary complaints may be assisted by pulse oximetric
analysis, arterial blood gas determination, sputum culture, Gram
staining and acid-fast staining of sputum, blood culture, and chest
radiography. Pulmonary radiographic findings are helpful in determining
likely causes (Table 149-3). Admission should
be considered for patients with new-onset pulmonary symptoms, especially
in the presence of hypoxia. Decisions regarding patients with known
pulmonary involvement are based on comparison with baseline status,
the effectiveness of ongoing or previous treatment, and the individual’s
ability to obtain outpatient follow-up. The study population from
which the Patient Pneumonia Outcome Research Team (PORT) criteria35 for
community-acquired pneumonia were derived did not include
HIV-positive patients, and therefore these criteria should not be
applied to HIV patients.
Table 149-3 Chest
Radiographic Abnormalities: Differential Diagnosis in the Acquired
Immunodeficiency Syndrome Patient |Favorite Table|Download (.pdf)
Table 149-3 Chest
Radiographic Abnormalities: Differential Diagnosis in the Acquired
Immunodeficiency Syndrome Patient
|Diffuse interstitial infiltration||Pneumocystis jiroveci (P. carinii )
|Mycobacterium tuberculosis infection|
|M. avium-intracellulare complex infection|
|Lymphoid interstitial pneumonitis|
|Focal consolidation||Bacterial pneumonia|
|Mycoplasma pneumoniae infection|
|P. jiroveci infection|
|M. tuberculosis infection|
|M. avium-intracellulare complex infection|
|Nodular lesions||Kaposi sarcoma|
|M. tuberculosis infection|
|M. avium-intracellulare complex infection|
|Cavitary lesions||P. jiroveci infection|
|M. tuberculosis infection|
|M. tuberculosis infection|
PCP is the most common opportunistic infection among
AIDS patients.36 The causal agent is known as P.
jiroveci or P. carinii. The older name, P.
carinii, is still in common usage. Approximately 70% of
HIV-infected patients acquire PCP at some time during their illness,
and PCP is often the initial opportunistic infection that establishes the
diagnosis of AIDS. This disease is the most frequent serious complication
of HIV infection in the U.S. and the most common identifiable cause of
death in patients with AIDS. The classic presenting symptoms of
PCP are fever, cough (typically nonproductive), and shortness of
breath (progressing from being present only with exertion to being
present at rest).
Symptoms are often insidious and accompanied by fatigue. Chest
radiographs most often show diffuse interstitial infiltrates (Table 149-3). Negative radiographic findings
are reported in 15% to 20% of patients
with PCP.37 In patients with nondiagnostic radiographic
findings and signs and symptoms suggestive of PCP, further testing
should be pursued. The lactate dehydrogenase level is elevated in
patients with PCP, but the test for lactate dehydrogenase has relatively
low sensitivity and specificity, which makes its use in the ED impractical.
Arterial blood gas analysis usually demonstrates hypoxemia and an
increase in the alveolar-arterial gradient. Early PCP should be
suspected if a patient demonstrates a decrease in pulse oximetric
values with exercise. Presumptive diagnosis of PCP is often
made in the ED if there is hypoxia without any other explanation. Inpatient
diagnostic testing may include bronchoscopy with lavage, biopsy,
and culture or examination of induced sputum by indirect immunofluorescence
using monoclonal antibodies.
Initial therapy for PCP is trimethoprim-sulfamethoxazole (Table 149-2) PO or IV for 3 weeks (typical
oral dosage is 2 (DS) tablets three
times daily). Adverse reactions, including rash, fever, and neutropenia,
occur in up to 65% of AIDS patients. Pentamidine is an alternative
agent (Table 149-2). Give steroids to patients
with a partial pressure of arterial oxygen of <70 mm Hg or an
alveolar-arterial gradient of >35 mm Hg. The usual regimen is oral
prednisone starting at 40 milligrams twice daily and tapering over
21 days (Table 149-2).
Seventy percent of patients have reinfection within 18 months.
Prophylactic therapy is an important step in preventing reinfection
and also has been shown to reduce the risk of developing bacterial
pneumonia. Oral trimethoprim-sulfamethoxazole, 1 DS tablet daily,
is the preferred agent. Prophylaxis is also recommended for all
patients with CD4+ T-cell counts of <200 cells/mm3.
Repeat infections may be less responsive to therapy.
The incidence of TB in the AIDS population is estimated to be
200 to 500 times that in the general population.38 Prevalence
studies demonstrate significant regional variations, attributed
to both the demographic characteristics of the populations and the
efficacy of local public health control measures. Clinical manifestations
of TB in HIV-infected patients vary significantly according to the
severity of immunosuppression. TB frequently occurs in patients
with CD4+ T-cell counts of 200 to 500 cells/mm3. Classic
pulmonary manifestations include cough with hemoptysis, night sweats,
prolonged fevers, weight loss, and anorexia. With worsening immunosuppression,
atypical and extrapulmonary manifestations are more common. Frequent
sites of dissemination are peripheral lymph nodes, bone marrow,
and the urogenital system. Classic upper lobe involvement and cavitary
lesions are less common, particularly among patients with late-stage
AIDS.38 Negative purified protein derivative TB
test results are frequent among AIDS patients due to immunosuppression.
Definitive diagnosis may be made by stain and culture of sputum,
although in some cases bronchoscopy with biopsy may be required.
In the ED, maintain a high index of suspicion for TB among
HIV-infected patients with pulmonary symptoms due to the high rates
of person-to-person transmission. Place the patient in an
isolation room in the ED until the diagnosis is ruled out.39 Base
the decision for further isolation on results of chest radiography
and detailed historical and clinical information. Current treatment
guidelines recommend a four-drug initial empirical therapy (Table 149-2; see Chapter 70, Tuberculosis).40,41 Multidrug-resistant
TB remains an issue of concern and should increase the awareness
of the need for early isolation. All HIV-infected patients with
positive purified protein derivative test results should receive
prophylaxis with isoniazid plus pyridoxine for 9 to 12 months; alternatives include
rifampin or rifabutin for 4 months. Empiric treatment should be given
to HIV-infected persons with close contact with a patient with active
Bacterial pneumonia is the most common pulmonary infection
in HIV-infected patients. Common pathogens include S.
pneumoniae, Haemophilus influenzae, and Staphylococcus aureus.
Productive cough, leukocytosis, and the presence of a focal infiltrate
suggest bacterial pneumonia, especially in those with earlier-stage disease.
The response to empirical therapy tends to be good; a specific diagnosis
can be established by Gram staining and culture.
Fungal Pneumonia and
Other Lung Disorders
Patients with severe immunosuppression are predisposed to disseminated
fungal infections such as those caused by C. neoformans and Aspergillus
fumigatus. Other noninfectious disorders of the lung seen
in HIV-infected patients include neoplasms (e.g., Kaposi sarcoma)
and lymphocytic interstitial pneumonitis. CMV or MAC infections
are unlikely unless the CD4+ T-cell count drops to <50
Cardiovascular complications are common in late-stage disease
but are difficult to diagnose in the ED. Cardiovascular complications
may be related to opportunistic infections, structural defects,
or drug toxicity. HIV-associated cardiovascular conditions include
cardiomyopathy, infective endocarditis (in injection drug users;
see Chapter 150, Infective Endocarditis),
pericardial effusion, congestive heart failure, coronary artery
disease, arrhythmias, and HIV-associated pulmonary hypertension. After
standard ED workup for these conditions, consultation with a cardiologist
and infectious disease specialist may be indicated.
GI complications of HIV infection are common. Approximately 50% of AIDS
patients present with GI complaints at some time during their illness.
The most frequent presenting symptoms include odynophagia, abdominal
pain, bleeding, and diarrhea. ED evaluation should focus on recognizing
the severity of symptoms and performing appropriate initial diagnostic
studies. Therapy should include volume and electrolyte repletion
and initiation of antibiotic therapy when appropriate. Disposition
is based on the duration of symptoms, the clinical appearance of
the patient, and the response to ED therapy.
Oral and Esophageal
Oral lesions are common in HIV-infected patients, frequently
contributing to malnutrition. The appearance of oral lesions in
HIV patients may serve as a potential clinical marker for viral
load and degree of immunodeficiency.43 Oral candidiasis,
or thrush (Figure 149-2), affects >80% of AIDS
patients. The tongue and buccal mucosa are commonly involved, and
the plaques are easily scraped from an erythematous base. Differentiation
from hairy leukoplakia (usually manifested as adherent, white, thickened
lesions on the lateral tongue borders) is challenging, but microscopic
examination of a potassium hydroxide smear can be used to confirm
the diagnosis. The development of oral candidiasis is a poor prognostic
sign and is predictive of progression to AIDS. Most oral lesions
can be managed symptomatically on an outpatient basis. Clotrimazole or nystatin
suspension or troches (five times daily) is the preferred treatment.
Refractory or recurrent disease can be managed with oral fluconazole.
Amphotericin B is reserved for severe cases.
Oral candidiasis (thrush). Extensive thrush is seen on the
hard and soft palate of this immunocompromised patient. (Photograph
contributed by Lawrence B. Stack. Reproduced with permission from Knoop
KJ, Stack LB, Storrow AB, Thurman RJ: The Atlas
of Emergency Medicine, 3rd ed, © 2009,
McGraw-Hill Inc., New York.)
Other causes of painful oral and perioral lesions include oral
hairy leukoplakia, HSV infection, and Kaposi sarcoma. HSV infection
usually can be recognized by the presence of typical vesicular lesions,
with diagnosis confirmed by identification
of multinucleated giant cells in scrapings or by culture. Both HSV
infection and hairy leukoplakia are responsive to oral acyclovir.
Oral Kaposi sarcoma appears as a nontender, well-circumscribed, slightly
raised violaceous lesion. Diagnosis requires biopsy. Topical treatments
may be palliative.
Esophageal involvement may occur with Candida, HSV,
and CMV infection. Complaints of odynophagia or dysphagia are usually
indicative of esophagitis, and these symptoms may be extremely debilitating.
Disease typically occurs in patients who have oral thrush and CD4+ T-cell
counts of <100 cells/mm3.
Treatment of esophagitis in the ED is presumptive. Endoscopy, histologic
staining and culture of lesions, and biopsy are reserved for patients
who fail to respond to therapy or have atypical presentations. Presumptive
treatment for esophageal candidiasis is oral
fluconazole (Table 149-2) or oral ketoconazole
(200 to 400 milligrams/d for 2 to 3 weeks). IV caspofungin
or IV amphotericin B may be used when oral treatment fails.44 Treatment
failures require endoscopy. CMV and HSV infections discovered by
endoscopy are treated with ganciclovir and acyclovir, respectively.
Diarrhea is the most frequent GI complaint. Causes include bacteria
(Shigella, Salmonella, enteroadherent Escherichia
coli, Entamoeba histolytica, Campylobacter, M.
avium-intracellulare complex, Clostridium difficile,
and others), parasites (Giardia lamblia, Cryptosporidium, Isospora
belli, and others), viruses (CMV, HSV, HIV, and others),
and fungi (H. capsulatum, C. neoformans,
and others). In many cases, a pathogen is never found. Diarrhea
is also a known side effect of protease inhibitors, most notably
nelfinavir and ritonavir.
ED evaluation of patients with diarrhea should include microscopic
examination of stool for leukocytes, ova, and parasites and acid-fast
staining and bacterial culture of stool. Clinical clues regarding
the cause of diarrheal illnesses may be provided by patient history
and confirmed by supplementary testing. Results usually are not
available during the ED visit. Bacterial infections generally follow
a more acute and fulminant course, whereas parasitic infections
are more frequently indolent. If bacterial infection is suspected,
empirical treatment with ciprofloxacin, which covers the common
bacterial pathogens, can be started. Cryptosporidium and Isospora infections
are common parasitic causes and are associated with profuse watery
diarrhea. Both organisms can be identified by modified acid-fast
staining of a stool specimen. I. belli infection
is usually responsive to trimethoprim-sulfamethoxazole, but relapse
is common. Cryptosporidiosis is difficult to treat, so consult an infectious
In patients with end-stage disease, the most common pathogens
are CMV and M. avium-intracellulare complex. Diagnosis
of both infections usually requires biopsy. Prolonged antimicrobial
therapy is indicated for treatment. Resistance and relapse are frequent
for both infections. About 15% of patients with late-stage
AIDS experience severe, high-volume watery diarrhea for which no
pathogen is identified even after thorough investigation. The presumed
diagnosis is AIDS-related enteropathy. Patients often require admission
for correction of electrolyte abnormalities and rehydration. Octreotide, the
somatostatin analog, may be helpful in some cases.
ED management consists of repletion of fluid and electrolytes.
Patients who appear nontoxic and can tolerate liquids can be referred
for outpatient follow-up to obtain test results. Patients with severe
diarrhea who do not require antibiotics may benefit from symptomatic
therapy, such as attapulgite (Kaopectate), psyllium (Metamucil),
and, if necessary, diphenoxylate hydrochloride with atropine (Lomotil).
Hepatomegaly occurs in approximately 50% of AIDS patients.
Elevation of the alkaline phosphatase level is seen frequently.
Jaundice is rare. Coinfection with hepatitis B virus and hepatitis C
virus is common, especially among injection drug users. Opportunistic
infection with CMV, Cryptosporidium, M.
avium-intracellulare complex, and M. tuberculosis also
may cause hepatitis.
Anorectal disease is common in AIDS patients. Proctitis is characterized by
painful defecation, rectal discharge, and tenesmus. Common causative
organisms include Neisseria gonorrhoeae, Chlamydia
trachomatis, Treponema pallidum, and HSV.
Proctocolitis includes the same symptoms as well as diarrhea, and
multiple bacterial organisms may be responsible (most commonly Shigella, Campylobacter,
and E. histolytica). Diagnostic evaluation should
include anoscopy with microscopic examination, Gram staining, and
culture of pus and/or stool.
Renal insufficiency among AIDS patients may be secondary to prerenal azotemia,
drug nephrotoxicity, or HIV-associated nephropathy. Renal tubular
acidosis is common and may explain a finding of hyperchloremic metabolic
acidosis. Indinavir therapy is a common cause of nephrolithiasis.
Management decisions should be made in conjunction with a nephrologist.
Generalized cutaneous conditions, such as xerosis (dry skin),
seborrheic eczema, and pruritus, are common and may develop before
opportunistic infections. Treatment is with emollients and, if necessary,
mild topical steroids. Pruritus may respond to oatmeal baths and
antihistamines. Other infections, including S. aureus infection
(manifested as bullous impetigo, ecthyma, or folliculitis), Pseudomonas
aeruginosa infection (which may present with chronic ulcerations
and macerations), and syphilis, may be manifest and should be treated
with standard therapies. Methicillin-resistant S. aureus colonization
and infection are prevalent and are associated with low CD4+ cell
counts.45 Several specific dermatologic conditions
are discussed in more detail in the following sections.
Kaposi sarcoma appears more often in homosexual men
than in other risk groups. Clinically, it consists of painless,
raised, brown-black or purple papules and nodules that do not blanch.
Common sites are the face, chest, genitals, and oral cavity, but
widespread dissemination involving internal organs may occur. Because
cutaneous Kaposi sarcoma is not generally associated with morbidity
or mortality, therapy is indicated only for extensive, painful,
or cosmetically disfiguring lesions. Cryotherapy or radiation can
be used for localized disease; widespread disease may be responsive
to chemotherapy with vincristine, vinblastine, or doxorubicin.
HSV infections are common and may be localized or systemic.
In patients with significant immunosuppression, infection may become
progressive, with chronic ulcerative mucocutaneous lesions. Diagnosis
and treatment are the same as for other patients with HSV infection
(see Chapter 144, Sexually Transmitted Diseases).
IV therapy with acyclovir is needed for extensive disease. Recommended regimens
are described in Table 149-2.
Reactivation of varicella-zoster virus is more common
in patients with HIV infection and AIDS than in the general population.
The clinical course is prolonged, and complications are more frequent.
In HIV-positive patients, oral acyclovir, famciclovir, or valacyclovir
is usually sufficient (Table 149-2). However,
in patients with disseminated disease or ophthalmic herpes zoster,
admission is indicated for IV acyclovir.
Intertriginous infections with either Candida or Trichophyton are
seen frequently in HIV-positive patients and can be diagnosed by
microscopic examination of potassium hydroxide preparations of lesion
scrapings. Treatment is with topical imidazole creams, such as clotrimazole,
miconazole, or ketoconazole.
Scabies occurs in about 20% of HIV-infected
patients, but classic intertriginous lesions are less common. Any
patient with a scaly, persistent pruritic eruption should be treated
with permethrin 5% cream, ivermectin, or crotamiton. Norwegian
scabies may be seen in immunosuppressed patients, and patients
typically exhibit extensive hyperkeratosis and crusting of the hands,
feet, and scalp. Pruritus is less impressive than is seen in typical
scabies. Extensive mite proliferation and high contagion are common. Treatment
failures and secondary infection also are common.
Human papillomavirus infections occur with increased
frequency in immunocompromised patients. Treatment is cosmetic or
symptomatic and may include cryotherapy, topical therapy, or laser
therapy. Other dermatologic conditions that occur with increased frequency
among HIV-infected patients include psoriasis, atopic dermatitis,
and alopecia. Referral for dermatologic consultation is appropriate.
Hypersensitivity reactions to medications occur commonly and
may include urticaria, maculopapular rash, or Stevens-Johnson syndrome.
Causative agents should be discontinued and supportive therapy initiated.
Persons at highest risk for HIV infection (i.e., injection drug
users and homosexual men) frequently experience mood disturbances
prior to, and after, contracting HIV. Infection with HIV results
in brain injury and is associated with a variety of CNS and metabolic
disturbances that can produce psychiatric symptoms. HIV infection
is also a significant psychosocial stressor, leading to social isolation,
poverty, and hopelessness.
Evaluation of psychiatric symptoms in the ED should focus on
an aggressive search for underlying organic causes of the acute
presentation.46 Delirium suggests an organic disorder
or a withdrawal syndrome, and the appropriate metabolic and imaging
evaluation is required. Patients with AIDS psychosis develop hallucinations,
delusions, or other behavioral changes. Treatment has been identical
to that for other psychoses. For acute episodes, admission is required.
Depression occurs in 20% of patients, most commonly
in those with lower CD4+ T-cell counts.47 Depressive
illnesses are often responsive to hospitalization and psychosocial
intervention. Antidepressant therapy may be considered if symptoms
of depression continue for >2 weeks. However, due to the increased
propensity of these patients to develop medication side effects,
close patient monitoring is required. Patients with suicidal ideation
usually require inpatient psychiatric management.
An increased incidence of mania is observed in both the early
and late stages of HIV infection. Late-stage mania is closely associated
with dementia and carries a poor prognosis. Management of HIV-positive
patients with psychiatric complaints must include attention to violent behavior
and suicidality. Assessment and stabilization may require use of physical
restraints and acute pharmacologic intervention. Neuroleptics and
benzodiazepines may be used in combination.
Sexually transmitted diseases (STDs) are epidemiologically associated with
HIV infection. Genital ulcers caused by diseases such as herpes, chancroid,
and syphilis are believed to provide vascular portals of entry for
HIV. Prevalence studies demonstrate a threefold to fivefold increased odds
ratio of HIV seropositivity in patients with genital ulcers.48 A
similarly increased risk of HIV infection has been found among patients with
gonorrhea and chlamydial infections. The prevalence of STDs, including
syphilis, is increasing.49 These studies, along
with recent ED-based prevalence surveys, have led to a recommendation
for increased surveillance of STDs as a means of controlling HIV
transmission.50 Patients with symptoms suggestive
of an STD should be tested for gonorrhea, chlamydial infection,
and syphilis. Serologic testing for syphilis should be performed
for all HIV-infected patients with any suspected STD. Some experts
recommend routine combined screening for HIV and STDs in the ED.51 Any
patient with known or suspected syphilis should be evaluated for
the possibility of neurosyphilis, which is known to have an increased
incidence in the HIV-infected population. Therapy for other STDs
is based on current CDC guidelines (see Chapter 144, Sexually Transmitted Diseases).
of HIV-Infected Patients
HIV-infected persons should not receive live virus or live
bacteria vaccines.52,53 The
one exception to this rule is the measles-mumps-rubella vaccine,
which does not have adverse effects in this population.
Killed vaccines pose no danger to immunosuppressed patients.54 Because
symptomatic HIV-infected persons have a suboptimal response to vaccines,
it is advised that all single-dose vaccines be given as early as possible
in the course of HIV infection. Table 149-4 summarizes
the CDC recommendations for common immunizations. Pneumococcal vaccine
is recommended for all patients >2 years of age, because the risk
for invasive pneumococcal infection is 50 to 100 times greater in
HIV-infected patients than in the general population. Tetanus-diphtheria
vaccine is recommended as a booster every 10 years for those who
have completed the primary series. Hepatitis B vaccine is recommended
for all high-risk individuals, including injection drug users, sexually
active homosexual men, and sexually active men and women who have
STDs or have had more than one sexual partner in the past 6 months.
Patients should be referred to a primary care provider for routine
Table 149-4 Immunization
Recommendations for Adult Human Immunodeficiency Virus–Infected
Patients |Favorite Table|Download (.pdf)
Table 149-4 Immunization
Recommendations for Adult Human Immunodeficiency Virus–Infected
|Tetanus-diphtheria toxoid||Every 10 y or, if injured, after 5 y|
|Measles-mumps-rubella||Not if immunocompromised (low CD4+ count*)|
|Meningococcal||One or more doses|
|Influenza (inactivated)||One dose annually|
|Hepatitis A||Two doses|
|Hepatitis B||Three doses|
|Varicella||Not if immunocompromised (low CD4+ count*)|
The most notable recent advance in the management of HIV is the
advent of HAART in 1996. After the introduction of HAART, sharp
declines in AIDS incidence occurred through 1999, and the number
of deaths among persons with AIDS has declined steadily.4,55
The fundamental goal of HIV therapeutics is long-term management
of a chronic infection. Specific treatment recommendations are evolving constantly
based on both advances in drug modalities and increasing information
from clinical trials on response to therapy. General therapeutic
goals, which remain constant, include the following: (1) clinical: prolong
life and improve the quality of life; (2) virologic: reduce viral load
as much as possible to halt disease progression and prevent or reduce
the development of resistant variants; (3) immunologic: promote immune
reconstitution, both quantitative (CD4+ T-cell count) and qualitative
(pathogen-specific immune response); and (4) therapeutic: achieve
a rational sequencing of drugs to attain virologic goals while reducing
side effects and maintaining therapeutic options.
The emergency physician should be familiar with general classes
of antiretroviral drugs, principles for initiating therapy, and
common adverse reactions. A complete drug list and up-to-date guide
for the general classes of antiretroviral drugs, principles for
initiating therapy, and common adverse reactions can be found on
the CDC Web site (http://www.cdc.gov/hiv/pubs/mmwr.htm).
The five main classes of antiretroviral drugs are (1) nucleoside
reverse transcriptase inhibitors, which interfere with the action
of reverse transcriptase (e.g., zidovudine); (2) non-nucleoside
reverse transcriptase inhibitors, which bind to reverse transcriptase
and block RNA- and DNA-dependent DNA polymerase activity (e.g.,
efavirenz); (3) protease inhibitors, which block HIV protease, a
key enzyme in establishing HIV infectivity (e.g. indinavir); (4)
entry inhibitors, which prevent HIV entry into cells by targeting
specific viral surface proteins or their corresponding receptors
(e.g. enfuvirtide); and (5) integrase inhibitors, which work by blocking
integrase, a protein that HIV needs to insert its viral genetic material
into the genetic material of an infected cell (e.g. raltegravir). Twenty-three
antiretroviral drugs are currently approved by the FDA.
Initial preferred treatment regimens include at least three drugs,
and possibly four drugs, as follows: two nucleoside reverse transcriptase
inhibitors plus one or two protease inhibitors,
or one non-nucleoside reverse transcriptase inhibitor. Factors that
are considered in initiation include likelihood of adherence to
the drug regimen, potential for long-term side effects, potential
for drug interaction, and preservation of future treatment options.
The current consensus recommends mandatory treatment for HIV-infected
patients with CD4+ cell counts of <350 cells/mm3 or
with a history of AIDS-defining illness.56,57 Other
indications for initiation of antiretroviral therapy regardless
of CD4+ count include pregnancy, HIV-associated nephropathy,
and hepatitis B virus coinfection requiring treatment.58 Education
and counseling also constitute an integral part of antiretroviral
therapy. For these reasons, decisions regarding initiation of and
changes in antiretroviral therapy always should be made in consultation
with the primary care physician and an infectious disease consultant.