David M. Cline
Risk factors for HIV infection include unprotected sexual activity, injection drug use, blood transfusion before 1985, and maternal–neonatal transmission.
EPIDEMIOLOGY
Increasing use of ED services by HIV-infected persons is due in part to changes in the demographic distribution of HIV cases and acquired immunodeficiency syndrome (AIDS)–related illnesses.
Seroprevalence studies in one inner-city ED reflect these trends, with rates of HIV infection among unse-lected adult patients rising from 6% to 11.4% over a 4- year period.
The range of seroprevalence across the United States is 2% to 14% among adult ED patients.
PATHOPHYSIOLOGY
HIV is a cytopathic retrovirus that kills infected cells. The viral genes are carried as a single-stranded RNA molecule within the viral particle. Following infection, the virus selectively attacks host cells involved in immune function, primarily CD4 T lymphocytes.
As a result of infection, immunologic abnormalities eventually occur, including lymphopenia, qualitative CD4 T-lymphocyte function defects, and autoimmune phenomena. Profound defects in cellular immunity ultimately result in a variety of opportunistic infections and neoplasms.
Transmission of HIV has been shown to occur via semen, vaginal secretions, blood or blood products, breast milk, and transplacental transmission in utero.
CLINICAL FEATURES
Acute HIV infection, essentially indistinguishable from a “flulike” illness, usually goes unrecognized but is reported to occur in 50% to 90% of patients.
The time from exposure to onset of symptoms is usually 2 to 4 weeks, and the most common symptoms include fever (>90%), fatigue (70%-90%), sore throat (>70%), rash (40%-80%), headache (30%-80%), and lymphadenopathy (40%-70%).
Other reported symptoms include myalgias, diarrhea, and weight loss. Seroconversion, reflecting detectable antibody response to HIV, usually occurs 3 to 8 weeks after infection.
This is followed by a long period of asymptomatic infection except for possible persistent generalized lymphadenopathy.
Early symptomatic infection is characterized by conditions that are more common and more severe in the presence of HIV infection but, by definition, are not AIDS indicator conditions.
Examples include thrush, persistent vulvovaginal candidiasis, peripheral neuropathy, cervical dyspla-sia, recurrent herpes zoster infection, and idiopathic thrombocytopenic purpura. At this time CD4 counts are 200 to 500 cells/mm3. As the CD4 count drops below 200 cells/mm3, the frequency of opportunistic infections dramatically increases.
AIDS is defined by the appearance of any indicator condition (Table 94-1) including a CD4 count lower than 200 cells/mm3.
Late symptomatic or advanced HIV infection exists in patients with a CD4 count lower than 50 cells/mm3 or clinical evidence of end-stage disease, including disseminated Mycobacterium avium complex or disseminated cytomegalovirus.
In today’s era of highly active antiretroviral therapy (HAART), longevity is more dependent on age and other comorbidities than HIV status, provided the patient adheres to HAART and the therapy is effective in suppressing viral load and maintaining normal CD4 counts.
TABLE 94-1 Indicator Conditions for Case Definitions of Acquired Immunodeficiency Syndrome
Esophageal candidiasis
Cryptococcosis
Cryptosporidiosis
Cytomegalovirus retinitis
Herpes simplex virus
Kaposi sarcoma
Brain lymphoma
Mycobacterium avium complex infection
Pneumocystis jiroveci (P. carinii) pneumonia
Progressive multifocal leukoencephalopathy
Brain toxoplasmosis
HIV encephalopathy
HIV wasting syndrome
Disseminated histoplasmosis
Isosporiasis
Disseminated Mycobacterium tuberculosis disease
Recurrent Salmonella septicemia
Added in 1993:
CD4+ T-cell count of <200 cells/mm3
Pulmonary tuberculosis
Recurrent bacterial pneumonia
Invasive cervical cancer
Abbreviation: HIV = human immunodeficiency virus.
CONSTITUTIONAL SYMPTOMS AND FEBRILE ILLNESSES
Systemic symptoms, such as fever, weight loss, and malaise, are common in HIV-infected patients and account for most HIV-related ED presentations.
Appropriate laboratory investigation includes electrolytes, complete blood count, blood cultures, urinalysis and culture, liver function tests, chest radiographs, and in selected patients, serologic testing for syphilis, cryptococcosis, toxoplasmosis, cytomegalovirus, and coccidioidomycosis.
Lumbar puncture should be considered if there are neurologic signs or symptoms or unexplained fever.
In HIV patients without obvious focalizing signs or symptoms, sources of fever vary by stage of disease.
Patients with CD4 counts higher than 500 cells/mm3 generally have sources of fever similar to those in nonimmunocompromised patients.
Those with CD4 counts between 200 and 500 cells/mm3 are most likely to have early bacterial respiratory infections.
For patients with CD4 counts lower than 200 cells/mm3, likely infections include Pneumocystis pneumonia (PCP; actually P. jiroveci), central-line infection, M. avium complex (MAC), Mycobacterium tuberculosis, cytomegalovirus, drug fever, and sinusitis.
Disseminated MAC occurs predominately in patients with CD4 counts below 100 cells/mm3. Persistent fever and night sweats are typical.
Associated symptoms of disseminated MAC include weight loss, diarrhea, malaise, and anorexia.
Diagnosis is made with acid-fast stain of stool or other body fluids or culture.
A more focal and invasive form of MAC has emerged, called immune reconstitution illness to MAC, which presents with lymphadenitis and follows weeks to months after starting HAART.
Cytomegalovirus is the most common cause of serious opportunistic viral disease in HIV-infected patients. Disseminated disease commonly involves the gastrointestinal or pulmonary system.
The most important manifestation is cytomegalovirus retinitis.
Infective endocarditis is a concern especially in intravenous (IV) drug users (see Chapter 95).
Non-Hodgkin lymphoma is the most commonly occurring neoplasm in HIV patients and typically presents as a high-grade, rapidly growing mass lesion.
PULMONARY COMPLICATIONS
Pulmonary presentations are among the most common reasons for ED visits by HIV-infected patients.
The most common causes of pulmonary abnormalities in HIV-infected patients include community-acquired bacterial pneumonia, PCP, M. tuberculosis, cytomegalovirus, Cryptococcus neoformans, Histoplasma capsulatum, and neoplasms.
Nonopportunistic bacterial pneumonias outnumber atypical infections including Streptococcus pneumo-niae (most common), 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.
Evaluation should include pulse oximetry, arterial blood gas analysis, sputum culture and Gram stain, acid-fast stain, blood cultures, and chest radiograph.
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).
Negative radiographs are reported in 15% to 20% of patients. Hypoxia or increased alveolar–arterial oxygen gradient identifies patients at risk.
Classic pulmonary manifestations of tuberculosis (TB) include cough with hemoptysis, night sweats, prolonged fevers, weight loss, and anorexia.
TB is common in patients with CD4 counts between 200 and 500 cells/mm3. Classic upper lobe involvement and cavitary lesions are less common, particularly among late-stage AIDS patients.
False-negative purified protein derivative TB test results are frequent among AIDS patients due to immunosuppression.
There is a high index of suspicion for TB in HIV patients with pulmonary symptoms due to high rates of person-to-person transmission.
Consider disseminated fungal infection in the severely immunosuppressed.
NEUROLOGIC COMPLICATIONS
Central nervous system (CNS) disease occurs in 90% of patients with AIDS, and 10% to 20% of HIV-infected patients initially present with CNS symptoms.
ED evaluation includes neuro examination, computed tomography, and lumbar puncture.
Cerebrospinal fluid studies should include pressures; complete cell count; glucose; protein; Gram stain; India ink stain; bacterial, viral, and fungal cultures; toxoplasmosis; and Cryptococcus antigen and coc-cidioidomycosis titer.
Common causes of neurologic symptoms include AIDS dementia, Toxoplasma gondii, and C. neoformans.
Symptoms may include headache, focal neurologic deficits, altered mental status, or seizures.
AIDS dementia complex (also referred to as HIV encephalopathy or subacute encephalitis) is a progressive process commonly heralded by subtle impairment of recent memory and other cognitive deficits caused by direct HIV infection.
Other, less common CNS infections that should be considered in the presence of neurologic symptoms include bacterial meningitis, histoplasmosis (usually disseminated), cytomegalovirus, progressive multifo-cal leukoencephalopathy, herpes simplex virus, neurosyphilis, and TB.
HIV patients may experience HIV neuropathy characterized by painful sensory symptoms of the feet.
GASTROINTESTINAL COMPLICATIONS
The most frequent presenting symptoms include odynophagia, abdominal pain, bleeding, and diarrhea.
ED evaluation includes stool for leukocytes, ova, parasites, acid-fast staining, and culture.
Diarrhea is the most frequent gastrointestinal complaint and is estimated to occur in 50% to 90% of AIDS patients. Common causes include bacterial organisms, such as Shigella, Salmonella, enter-oadherent Escherichia coli, and Campylobacter; parasitic organisms; viruses; fungi; and antiviral therapy.
Oral candidiasis, or thrush, affects more than 80% of AIDS patients.
The tongue and buccal mucosa are commonly involved, and the plaques characteristically can be easily scraped from an erythematous base (see Fig. 94-1). Esophageal involvement may occur with Candida, herpes simplex, and cytomegalovirus. Complaints of odynophagia or dysphagia are usually indicative of esophagitis and may be extremely debilitating.
Hepatomegaly occurs in approximately 50% of AIDS patients. Elevation of alkaline phosphatase levels is frequently seen. Jaundice is rare. Coinfection with hepatitis B and hepatitis C is common, especially among IV drug users.
Anorectal disease is common in AIDS patients. Proctitis is characterized by painful defecation, rectal discharge, and tenesmus.
Common causative organisms include Neisseria gon-orrhoeae, Chlamydia trachomatis, syphilis, and herpes simplex.
FIG. 94-1. 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.)
CUTANEOUS MANIFESTATIONS
Generalized conditions such as xerosis, seborrheic eczema, and pruritus are common.
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.
Reactivation of varicella zoster virus is more common in patients with HIV infection and AIDS than in the general population.
Herpes simplex virus infections are common. HIV patients may develop bullous impetigo and Pseudornonas-associated chronic ulcerations. MRSA infection, scabies, human papillomavirus, and hyper-sensitivity reactions to medications are common.
OPHTHALMOLOGIC MANIFESTATIONS
Seventy-five percent of patients with AIDS develop ocular complications.
Cytomegalovirus retinitis is the most frequent and serious ocular opportunistic infection and the leading cause of blindness in AIDS patients.
The presentation of cytomegalovirus retinitis is variable. It may be asymptomatic early on but later causes changes in visual acuity, visual field cuts, photophobia, scotoma, or eye redness or pain.
Herpes zoster ophthalmicus is another diagnosis to consider and is recognized by the typical zoster rash in the distribution of cranial nerve VI.
DIAGNOSIS AND DIFFERENTIAL
Benefits of early HIV diagnosis include early and aggressive antiretroviral therapy that can lead to immune reconstitution, prevention of viral mutation and drug resistance, slowing of disease progression, and improved long-term prognosis.
The most common assay used to detect viral antibody is a screening enzyme-linked immunoassay (ELISA) followed by a confirming Western blot test on ELISA-positive specimens.
ELISA is approximately 99% specific and 98.5% sensitive; the Western blot test is nearly 100% sensitive and specific if performed under ideal laboratory circumstances.
Diagnosis of acute-stage HIV infection is not possible with standard serologic tests because seroconversion has not yet occurred.
Methods for earlier detection of HIV-1 include techniques to detect DNA, RNA, or HIV antigens.
The single-use diagnostic system is used to screen rapidly for antibodies to HIV-1 in serum or plasma. Rapid tests are available in many EDs nationwide but must be confirmed with Western blot testing.
Knowledge of current or recent CD4 counts and a HIV viremia load will help in the management of HIV patients.
CD4 counts below 200 cells/mm3 and viral load greater than 50,000 copies/mL is associated with increased risk of progression to AIDS-defining illness.
When these levels are unavailable, a total lymphocyte count of <1200 cells/mm3 combined with clinical symptoms is strongly predictive of a positive CD4 count of <200 cells/mm3.
EMERGENCY DEPARTMENT CARE AND DISPOSITION
The initial evaluation of HIV-infected and AIDS patients begins with a heightened awareness of the need for universal precautions. Respiratory isolation should be instituted for patients with suspected TB.
All unstable patients should have airway management as indicated, oxygen, pulse oximetry, cardiac monitoring, and IV access.
Seizures, altered mental status, gastrointestinal bleeding, and coma should be managed with standard protocols.
Suspected bacterial sepsis and focal bacterial infections should be treated with standard antibiotics (see Chapter 91).
Systemic M. avium should be treated with clarithro-mycin 500 milligrams PO twice daily plus ethambutol 15 milligrams/kg PO daily plus rifabutin 300 milligrams PO daily.
Treatment of immune reconstitution illness to MAC should include continuation of HAART, antimicrobials as above, and possibly steroids.
Systemic cytomegalovirus should be treated with ganciclovir 5 milligrams/kg IV every 12 hours or foscarnet 90 milligrams/kg IV every 12 hours.
Ophthalmologic cytomegalovirus is treated with a ganciclovir implant plus ganciclovir 1.0 to 1.5 grams PO three times daily or 5 milligrams/kg IV twice daily for 14 to 21 days.
Pulmonary PCP should be treated with trimethoprim-sulfamethoxazole (TMP-SMX), with TMP 15 to 20 milligrams/kg/d IV or PO divided three times daily, for 3 weeks. The typical oral dose is two tablets of TMP-SMX double strength three times daily. An alternative is pentamidine 4 milligrams/kg/d IV or IM for 3 weeks.
Oral steroids should be given if hypoxic: prednisone 40 milligrams twice daily for 5 days, then 40 milligrams daily for 5 days, and then 20 milligrams daily for 11 more days.
Pulmonary TB may be treated with INH 5 milligrams/kg/d PO plus rifabutin 10 milligrams/kg/d PO or rifampin 10 milligrams/kg/d PO plus pyrazinamide 15 to 30 milligrams/kg/d PO plus ethambutol 15 to 20 milligrams/kg/d PO daily.
CNS toxoplasmosis can be treated with pyrimeth-amine 200 milligrams initially and then 50 to 75 milligrams daily PO plus sulfadiazine 4 to 6 grams daily PO plus folinic acid 10 milligrams daily PO for 6 to 8 weeks, plus/minus leucovorin 10 to 25 milligrams daily.
CNS cryptococcosis can be treated with amphotericin B 0.7 milligrams/kg/dose daily IV and flucytosine 25 milligrams/kg IV four times daily for 2 weeks. When improved, fluconazole 400 milligrams PO daily for 8 to 10 weeks can be used.
Candidiasis (thrush) can be treated with clotrimazole 10-milligram troches five times per day or nystatin 500,000 units/mL gargle with 5 mL five times per day.
Esophagitis can be treated with fluconazole 100 to 400 milligrams daily PO.
Salmonellosis can be treated with ciprofloxacin 500 milligrams PO twice daily for 2 to 4 weeks.
Cutaneous herpes simplex can be treated with acyclo-vir 200 milligrams PO five times daily for 7 days or famciclovir 125 milligrams PO twice daily for 7 days or valacyclovir 1 gram PO BID for 7 days or acyclovir 5 to 10 milligrams/kg IV every 8 hours for 7 days for severe illness.
Cutaneous herpes zoster can be treated with acyclovir 800 milligrams PO five times daily, or valacyclovir 1 gram PO three times daily, or famciclovir 500 milligrams PO three times daily.
Herpes zoster ophthalmicus should be treated with acyclovir 800 milligrams PO five times daily for 7 to 10 days.
Candida or Trichophyton should be treated with topical clotrimazole or miconazole or ketoconazole three times daily for 3 weeks.
Although rarely started in the ED, antiretroviral therapy is started for CD4 counts below 350 cells/mm3 or history of AIDS-defining illness (see Table 94-1) or pregnancy, HIV-associated neuropathy, and hepatitis B confection regardless of the CD4 count.
New protocols recommending treatment upon initial HIV-positive testing may be forthcoming, but are not currently available. Initial treatment includes two nucleoside reverse transcriptase inhibitors plus one or two protease inhibitors or one non-nucleoside reverse transcriptase inhibitor drug. See the Centers for Disease Control and Prevention Web site: http://www.cdc.gov/hiv/.
The decision to admit an AIDS patient should be based on severity of illness, with attention to new presentation of fever of unknown origin, hypoxia worse than baseline, or Pao2 below 60 mm Hg, suspected PCP, suspected TB, new CNS symptoms, intractable diarrhea, suspected cytomegalovirus retinitis, herpes zoster ophthalmicus, or a patient unable to perform self-care.
Post-exposure prophylaxis should be initiated as quickly as possible, preferably within 1 to 2 hours. Risks for seroconversion include (1) deep injury, (2) visible blood on the injuring device, (3) needle placement in a vein or an artery of the source patient, and (4) a source patient with late-stage HIV infection. Treatment regimes vary by type of exposure.
CDC guidelines recommend two general alternatives: a basic regimen, which consists of two-drug therapy, often consisting of azidothymidine and lamivudine, and an expanded regimen, which adds a third drug, such as indinavir or nelfinavir.
For further reading in Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 7th ed., see Chapter 149, “Human Immunodeficiency Virus Infection and Acquired Immunodeficiency Syndrome,” by Richard E. Rothman, Catherine A. Marco, and Samuel Yang.