The human immunodeficiency virus (HIV) is the leading cause of infectious disease deaths worldwide. As of 2013, approximately 36 million patients died of HIV-related illnesses, and an estimated 35.3 million people were living with HIV infection/acquired immunodeficiency syndrome (AIDS). Although HIV exists everywhere, the vast majority of new infections (95%) occur in individuals living in low- and middle-income countries. As an example, in sub-Saharan Africa, which is the world’s most affected region, nearly 1 in every 20 adults are living with HIV.¹

Despite the global burden, the number of new HIV infections is falling annually, as are deaths. These improvements result from a global health strategic approach.² In 2013, an estimated 1.3 million U.S. citizens had HIV.³ Despite the overall promising trends, the challenge of reducing new infections persists, with approximately 50,000 new cases occurring each year in the United States.

Risks associated with acquiring HIV infection include homosexuality or bisexuality, injection drug use, heterosexual exposure, receipt of a blood transfusion prior to 1985, and maternal HIV infection (risk for vertical and horizontal maternal–neonatal transmission). Rates of HIV attributable to male-to-male sexual contact increased from 55% in 2008 to 62% in 2011. Heterosexual contact accounts for approximately 28% of transmissions, followed by about 8% for injection drug use and 3% for male-to-male sexual contact and IV drug use. New HIV infection rates continue to rise among young disadvantaged minority populations (many of whom use the ED for both primary and emergency care). Although African Americans represent only 14% of the total U.S. population, this group accounted for almost half (44%) of new HIV infections in the year 2010. The rate of new infections among black men was the highest of any group by race and sex, notably in men having sex with men. Hispanics also have a higher proportion of new infections (21%) than accounted for by their relative size in the population (14%). Factors associated with the ethnic disparities in HIV include the overall higher prevalence of disease in minority populations, economic barriers that decrease access to testing and treatment, higher rates of incarceration (associated with increased concurrent relationships and higher levels of sexually transmitted infections, both of which increase likelihood of transmissions), and homophobia, which may impede HIV prevention.⁴ ED visits by HIV-infected individuals occur at rates higher than the general population⁵ due to the characteristics of the populations who use the ED, which are the same groups disproportionately affected by HIV/AIDS.

HIV is a cytopathic retrovirus that kills infected cells. The virus is labile and is neutralized easily by heat and common disinfecting agents such as 50% ethanol, 35% isopropyl alcohol, 0.3% hydrogen peroxide, or a 1:10 solution of household bleach. There are two major subtypes of HIV; HIV-1 is the predominant subtype worldwide and is the cause of AIDS. HIV-2 causes a similar immune syndrome but is restricted primarily to western Africa and is infrequent in the United States, but its incidence is growing.

The HIV virion is a central RNA molecule and a reverse transcriptase protein surrounded by a core protein encased by a lipid-bilayer envelope. After infection, HIV selectively attacks host cells involved in immune function, primarily CD4+ T cells. Within the host cell, HIV-encoded RNA is reverse-transcribed into DNA by the enzyme reverse transcriptase. The viral genome then becomes integrated into the host genome, where it may lie dormant or be actively transcribed and translated to produce virally encoded proteins and new HIV virions. As a result of infection, immunologic abnormalities eventually occur, including lymphopenia, qualitative CD4+ T-cell function defects, and autoimmune phenomena. Defects in cellular immunity ultimately result in development of a variety of opportunistic infections and neoplasms.

HIV exists in saliva, urine, cerebrospinal fluid (CSF), pus, brain, tears, alveolar fluid, synovial fluid, and amniotic fluid. Transmission of HIV occurs through semen, vaginal secretions, blood or blood products, and breast milk, and in utero by transplacental transmission. Transmission does not occur with casual contact. There is only one documented case of transmission from healthcare provider to patient in the United States, which involved an infected dentist in Florida who transmitted the virus to six patients.

Symptoms of acute HIV infection (also called acute retroviral syndrome) occur in 50% to 90% of infected patients. The diagnosis is missed in up to 75% of cases due to nonspecific presentation (resemblance to a flulike or mononucleosis-like syndrome) and a lack of suspicion. Symptoms of acute HIV infection usually develop 2 to 4 weeks after exposure and may last for 2 to 10 weeks and include fever (>90%), fatigue (70% to 90%), pharyngitis (>70%), rash (40% to 80%), headache (30% to 70%), and lymphadenopathy (40% to 70%); other reported symptoms are weight loss, headache, and diarrhea.⁶

Seroconversion and detectable antibody response to HIV usually occur 3 to 8 weeks after infection, although delays of up to 11 months have been reported. This phase is followed by a long period of asymptomatic infection, during which patients generally have no findings on physical examination except for possible persistent generalized lymphadenopathy (enlarged lymph nodes in at least two noncontiguous sites other than inguinal nodes). The mean incubation time from exposure to the development of AIDS in untreated patients is estimated at 8.23 years for adults and 1.97 years for children <5 years of age. Virologic studies of patients during this period suggest that a steady state of HIV replication and CD4+ T-cell death and replacement exists until increased levels of HIV replication occur. Variables most predictive of disease stage are viral load and CD4+ T-cell counts, with a steeper decline in CD4+ T-cell count and a higher viral burden associated with more rapid progression and more outcomes. Other non–HIV-related factors, such as age and malignancy, also impact disease progression.

Early symptomatic infection is characterized by conditions that are more common and more severe in the presence of HIV infection but are not AIDS-indicator conditions. These include thrush, persistent vulvovaginal candidiasis, peripheral neuropathy, cervical dysplasia, recurrent herpes zoster, and idiopathic thrombocytopenic purpura. These conditions occur more often as the CD4+ T-cell count drops below 500 cells/mm³; if the count drops below 200 cells/mm³, the frequency of opportunistic infections increases dramatically. HIV infection is classified by the Centers for Disease Control and Prevention as stage 3 (AIDS) by either laboratory evidence or clinical evidence of disease⁷ (Table 154-1).

HIV TESTING METHODS

HIV infection is diagnosed using identification of HIV nucleic acid, detection of viral-specific antigen, detection of antibodies to HIV, and isolation of the virus by culture (now rarely used in practice). The standard and most commonly used testing method for HIV is detection of antibodies to the virus. Testing involves sequential use of an enzyme-linked immunosorbent assay, followed by a Western blot assay. Enzyme-linked immunosorbent assay is approximately 99% specific and 98.5% sensitive; Western blot testing is nearly 100% sensitive and specific if performed under ideal laboratory conditions. Enzyme-linked immunosorbent assay detects the binding of specific serum antibodies to HIV antigens that are adherent to a microtiter plate. Western blot assay detects HIV antibodies to discrete viral antigens that are electrophoretically separated and transferred to nitrocellulose paper. A positive Western blot result requires detection of at least one gene product, although criteria vary by laboratory. Reasons for indeterminate test results include early seroconversion, cross-reacting antibodies, pregnancy, presence of an autoimmune disease, or technical errors.

Acute HIV is the time from HIV transmission to seroconversion. Diagnosis of acute HIV infection cannot be made 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, although these tests are not always available in the ED. Mean times from transmission to detection are shortest for viral load (17 days), followed by p24 antigen (22 days), enzyme-linked immunosorbent assay positivity (25 days), and Western blot positivity (31 days).⁸

BENEFITS OF EARLY DIAGNOSIS

Although acute HIV infection is not diagnosed in up to 75% of all cases, the benefits of early recognition allow an opportunity to limit risk of further transmission (key in this high viral load period) and to start antiretroviral therapy to potentially reduce symptoms and slow disease progression.⁸ For patients in whom acute HIV infection is suspected but not confirmed (i.e., those with a high-risk profile presenting with fever of unknown origin and/or a syndrome suspicious for acute seroconversion), counseling and urgent referral from the ED to an outpatient follow-up setting for appropriate testing are best.

RAPID HIV TESTS

As of 2012, there were eight rapid HIV tests approved for use by the U.S. Food and Drug Administration.⁹ The first approved point-of-care rapid HIV test was Orasure HIV-1/2^®, and it is the only one that uses oral fluid. Sensitivity and specificity are comparable with those of standard serologic testing, and minimal training is required for administration. Relay any point-of-care results to the patient as preliminary positive if reactive, confirming with Western blot testing. Negative test results may miss patients in the window period before seroconversion has occurred; this requires a repeat test at 3 months.

THE NEW HIV TESTING ALGORITHM

In June 2014, the Centers for Disease Control and Prevention released new recommendations regarding laboratory testing practices for HIV.¹⁰ The new algorithm calls for use of automated testing for antibody to HIV-1 and HIV-2 simultaneously with detection of HIV-1 p24 antigen, permitting detection of acute infections. In instances where this set of tests is negative, no further testing is advised, and the patient is counseled that he or she tested negative. For those tests with positive results, follow-up testing differentiates HIV-1 and HIV-2. In cases where the differentiation test is negative, a nucleic acid amplification test confirms acute seroconversion. Turnaround time for the combined assay and HIV-1/2 differentiation assay is about 60 minutes. Turnaround time for confirmatory testing with nucleic acid amplification can take up to a few days. This new algorithm allows better early detection; ED-based studies show this is feasible and will detect new, acutely infected patients.^11,12

CD4+ T-CELL COUNTS

CD4+ T-cell counts of <200 cells/mm³ and a viral load of >50,000 copies/mm³ are associated with increased risk of AIDS-defining illnesses. These indices are also frequently used by the primary care physician or HIV specialist as indicators for initiation of antiretroviral therapy (although the threshold value for initiation of treatment is controversial). When this information is unavailable or the stage of disease is unknown, the total lymphocyte count approximates the CD4+ T-cell count. In a recent ED study, a total lymphocyte count <1700 cells/mm³ had a sensitivity of 95% for a CD4 count of <200 cells/mm³.¹³

HIV TESTING PRACTICES IN THE ED

Time limitations, cost, difficulty with follow-up, confidentiality requirements, and questions regarding reimbursement are barriers to HIV testing in the ED. The Centers for Disease Control and Prevention 2006 HIV testing guidelines¹⁴ offer a streamlined approach with decreased requirements for pretest counseling and use of opt-out testing (in which no separate written consent is required). State variability exists for both opt-out versus opt-in approaches and documentation requirements for informed consent. The U.S. Preventive Services Task Force gave a “Grade A” recommendation for routine HIV screening for all people age 15 to 65, as well as younger adolescents and older adults who are at an increased risk for HIV infection and all pregnant women, including those in labor whose HIV status is unknown. The Patient Protection and Affordable Care Act requires new insurance policies to pay for preventive services with “Grade A” recommendation.

American College of Emergency Physicians policy recognizes the need for ED HIV testing based on clinical need and supports screening with caveats. Currently, ED HIV testing in the United States remains relatively low (~0.2% of all ED visits), but programs are increasing, particularly in urban and/or academic centers. Determination of which of several approaches (e.g., nontargeted universal vs targeted) is most rational for ED practice is an area of active research, with local prevalence playing a role in the screening plan chosen.

INITIAL CARE: GENERAL CONSIDERATIONS

The spectrum of disease caused by HIV infection varies, from those coming to the ED with asymptomatic infection for symptoms unrelated to HIV disease, to symptomatic patients seeking care from involvement of virtually any organ system and with multiple coexisting symptoms. This makes the ED evaluation and diagnosis of HIV-positive patients challenging.

Maintain confidentiality regarding HIV-related diagnoses in the ED. Begin care without discrimination and without assuming any illness trajectory unless advanced directives, including cardiopulmonary resuscitation, are already in place.

Always use universal precautions (in some hospitals termed standard precautions). Healthcare workers are often exposed to the blood and body fluids of HIV-infected patients or patients at high risk of harboring the HIV virus. ED-based studies have demonstrated that substantial numbers of patients continue to have unsuspected HIV infection and that HIV seropositivity cannot be predicted accurately, even after assessment of risk factors.

Occupational exposure is covered in the chapter 162, “Occupational Exposures, Infection Control, and Standard Precautions.” Testing, treatment, and follow-up are discussed. Other resources for information on HIV exposures are the Centers for Disease Control and Prevention and the University of California, San Francisco National Clinicians’ Post-Exposure Prophylaxis Hotline (888-448-4911, http://www.nccc.ucsf.edu).¹⁵

Focus the history taking and physical examination on identifying the clinical stage of disease 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. A directed exam seeks findings of organ involvement related to the chief complaint. Physical findings that might specifically assist with staging include the presence of oral candidiasis, skin lesions, temporal wasting, and dementia.

Diagnosis and treatment are directed toward recognition of infection (when not previously diagnosed), assessment of the severity of disease, identifying specific organ(s) involved, and institution of therapy. For the most up-to-date information and details on drug dosing, sources include the Centers for Disease Control and Prevention Web site¹⁶ or the Johns Hopkins University School of Medicine guide to care of the HIV-positive patient.⁸

Consultation with an infectious disease specialist and others with expertise in HIV infection is often necessary to provide proper therapy and disposition. Disposition decisions are based on the need for inpatient evaluation or management and the patient’s ability to function as an outpatient, which is often driven by oral intake and ambulation ability and availability of appropriate medical follow-up. Healthcare and family resources can aid decision making about care.

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.⁸ In the ED, look for systemic infection, malignancy, drug toxicity, or metabolic abnormalities. This is done by assessing serum electrolytes with renal function, CBC, liver function studies, blood cultures, urinalysis and urine culture, hepatic function tests, and chest radiograph; serologic testing for syphilis, cryptococcosis, toxoplasmosis, cytomegalovirus infection, and coccidioidomycosis is deployed more selectively. Lumbar puncture is needed after neuroimaging if headache, altered sensorium, visual change, or other focal neurologic symptoms or signs are present.

When treating the febrile ill-appearing HIV patient, provide fluid resuscitation, prompt empiric antibiotics, 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, 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

Infections are the most common cause of hospitalization among HIV-infected persons. In HIV-infected persons 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. For patients with CD4+ T-cell counts of <200 cells/mm³, the most common causes of fever without obvious localizing findings are early Pneumocystis jirovecii pneumonia (formerly known as Pneumocystis carinii); central line infection; infection with Mycobacterium avium complex, Mycobacterium tuberculosis, or cytomegalovirus; drug fever; and sinusitis. Other 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 M. avium complex infection occurs predominantly in patients with CD4+ T-cell counts of ≤100 cells/mm³ and not on antiretroviral therapy or azithromycin prophylaxis. Persistent fever and night sweats are typical symptoms. 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 M. avium complex (and histoplasmosis) and should be ordered for patients with late-stage disease and fever of unknown origin. Treatment for M. avium complex reduces bacteremia and improves symptoms but does not eradicate disease; it starts with clarithromycin combined with ethambutol and rifabutin. Azithromycin is an alternative therapy.

Immune reconstitution inflammatory syndrome mimics an autoimmune event, with lymphadenitis, fever, and other symptoms commonly starting weeks to months after beginning antiretroviral therapy, often during tuberculosis therapy. Current treatment guidelines advise continuing antiretroviral therapy; nonsteroidal anti-inflammatory agents are recommended for mild to moderate cases; in severe cases, corticosteroids are advised (prednisone 1 to 2 milligrams/kg or equivalent for 1 to 2 weeks). Add the appropriate antimicrobials if there is a known or suspected infection.

Cytomegalovirus is a 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 154-2).