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Authors: Catherine A. Marco, MD, FACEP, Associate Professor, Department of Surgery, Medical College of Ohio; Attending Physician, St. Vincent Mercy Medical Center, Toledo, OH; Richard E. Rothman, MD, PhD, FACEP, Assistant Professor, Emergency Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; and Samuel Yang, MD, Instructor, Emergency Medicine, Johns Hopkins School of Medicine, Baltimore, MD.
Peer Reviewer: Andrew D. Perron, MD, FACEP, Associate Residency Director, Department of Emergency Medicine, Maine Medical Center, Portland.
Since the early 1980s, HIV and the AIDS epidemic have changed the way medicine is practiced. The disease debuted as a devastating and rapidly progressive syndrome that was uniformly fatal, with few interventions. With the widespread use of effective antiviral agents in the 1990s, HIV infection and AIDS became survivable, long-term illnesses. While much has been learned about the disease and its complications, much work still remains. HIV/AIDS is very much a global epidemic, no longer confined to populations living an alternative lifestyle. In the United States, women comprise the fastest-growing population with HIV, and heterosexual transmission accounts for the fastest-growing risk factor group.
The emergency physician plays a key role in the management of HIV. Emergency physicians encounter all phases of the illness, from counseling patients on safe sex practices to treating the medical complications of chronic immunosuppression. Despite all of the recent advances, HIV infection and AIDS remain challenging and continually evolving diseases. In this issue of Emergency Medicine Specialty Reports, the authors provide a comprehensive update on the diagnosis and clinical management of HIV infection and its complications.— The Editor
According to the Centers for Disease Control and Prevention’s (CDC) most recent definition, published in 1993, AIDS is the laboratory evidence of HIV infection plus at least one of the conditions listed in Table 1.1 While AIDS is a reportable disease in the United States, reporting of HIV infection is optional in most states, making HIV epidemiologic data more difficult to assess.
Worldwide estimates indicate that approximately 37 million adults and 2 million children were living with HIV/AIDS at the end of 2003.2 The vast majority of HIV-infected persons live in the developing world. In North America, there were an estimated 54,000 new cases of HIV reported in 2003, and an estimated 790,000-1.2 million persons are now living with HIV or AIDS. Within the United States, HIV-positive persons tend to be concentrated primarily in large urban settings.
The majority of cases in the United States have occurred in adult men (80%), as compared to adult women (18%) and children (1%). There is a disproportionate rate of infection among minority groups.3
Risk factors associated with acquiring HIV infection include men who have sex with men, injecting drug use (IDU), heterosexual exposure to a partner at risk, blood transfusion prior to 1985, and maternal-neonatal transmission. In recent years, there has been a relative decrease in newly acquired HIV in men who have sex with men, and a relative increase in incidence of HIV among injecting drug users and heterosexual contacts.
The HIV virus is a cytopathic human retrovirus. Several modes of transmission of HIV have been proven, including semen, vaginal secretions, blood products, breast milk, and transplacental transmission in utero. HIV selectively attacks cells within the immune system and this accounts for much of the immunodeficiency it produces in affected individuals.
HIV Testing in the ED
HIV infection most commonly is established by HIV serology, or detection of antibodies to the virus. Testing may be performed using enzyme-linked immunoassay (EIA) and a Western blot (WB) assay. Criteria for positive results are a repeatedly positive EIA followed by a positive WB. Overall, sensitivity and specificity of HIV serology is greater than 99.9%. False-negative HIV tests may occur during the window period (usually the first several months) of acute infection, after viral transmission but before the appearance of antibodies.
The single use diagnostic system (SUDS) assay is similar to EIA screening tests, and can be performed in approximately one hour. Another test is the OraQuick Rapid HIV-1 Antibody Test (OraSure Technologies, Inc., Bethlehem, PA). OraQuick is a simple, easy to use, point-of-care that can detect antibodies to HIV-1 in fingerstick or whole blood specimens.
Traditionally, serologic testing of patients for HIV in the ED had been discouraged. However, newer testing modalities have challenged this concept. It is well established that early recognition of HIV and early therapeutic intervention can significantly delay progression of disease, reduce risk of opportunistic infections, and lead to decreased morbidity and mortality. If ED screening is performed, sufficient resources should be in place to ensure appropriate pretest and posttest counseling, and outpatient referral.
Clinical Presentations Related to HIV Infection
Initial Evaluation and Stabilization. The initial evaluation should be tailored to identify emergent disorders requiring early intervention and stabilization. Airway, breathing, and circulation must be rapidly assessed and stabilized. Following initial stabilization, the remainder of the history and physical may be completed.
Primary HIV Infection. Acute HIV syndrome (acute seroconversion syndrome) commonly occurs 2-6 weeks following initial exposure and may cause nonspecific symptoms such as fever, adenopathy, fatigue, pharyngitis, diarrhea, weight loss, and rash. These relatively nonspecific symptoms may be present for 1-3 weeks, and many patients do not seek medical attention during this phase of illness.
Systemic Symptoms of HIV Infection. Systemic symptoms such as fever, weight loss, fatigue, and malaise are common among ED patients. The differential diagnosis is lengthy and includes a variety of infectious causes, malignancies, and drug reactions.
Fever is a common presenting complaint in patients with AIDS. Evidence of an infectious cause or other reason for fever should be sought by careful history and physical examination. Laboratory investigation of fever may be tailored to the individual patient and severity of symptoms, and may often include chest radiography, complete blood count (CBC), electrolytes, erythrocyte sedimentation rate, liver function tests, serologic test for syphilis, urinalysis and culture, and blood cultures (aerobic, anaerobic, and fungal). If there are neurologic signs or symptoms or if no other source of fever is identified, lumbar puncture should be performed after a cranial computed tomography (CT) scan or MRI. Many patients with fever or other systemic symptoms may be managed as outpatients, if adequate follow-up observation and home assistance are available. Indications for admission include toxic presentation, neutropenia with fever, hypoxia, dehydration, active bleeding, or other need for urgent diagnosis and treatment.
Neurologic Disease. Neurologic diseases are rarely the initial manifestation of AIDS, but the frequency of neurologic complications increases over the course of HIV infection, with 75-90% incidence patients with AIDS experiencing a neurologic disorder. The most common AIDS-defining neurologic complications are HIV encephalopathy, Cryptococcus neoformans, toxoplasmosis, and primary central nervous system (CNS) lymphoma. Other CNS infections may include bacterial meningitis, histoplasmosis, cytomegalovirus (CMV), progressive multifocal leukoencephalopathy (PML), herpes simplex virus (HSV), neurosyphilis, and TB. Noninfectious CNS processes include CNS lymphoma, cerebrovascular accidents, and metabolic encephalopathies.
The clinical picture in patients with serious neurologic complications often is nonspecific. The most common symptoms indicative of CNS pathology are headache, altered mental status, seizures, meningismus, and focal neurologic deficits. Most patients who present with neurologic complaints or findings should have a workup to include neuroimaging and possible lumbar puncture (LP). For those with focal deficits, new seizures, or suspicion of focal lesions, immediate neuroimaging is recommended, followed by LP. For most CNS processes that require immediate identification, CT without contrast is considered adequate to identify the majority of mass lesions.
Cryptococcus neoformans is a fungal CNS infection which occurs in 10% of HIV infected patients, and may cause either focal cerebral lesions or diffuse meningoencephalitis. It is found most commonly in those with CD4 counts of less than 100. Presenting symptoms may include fever and headache, often accompanied by nausea and vomiting. Less common symptoms include visual changes, dizziness, seizures, and cranial nerve deficits. Mortality may be up to 30%.
Emergent CT typically is unrevealing. Definitive diagnosis is made by a positive cryptococcal antigen in the cerebrospinal fluid (CSF), which is nearly 100% sensitive and specific. Other diagnostic tests include India ink staining (60-80% sensitive), fungal culture (95% sensitive), and serum cryptococcal antigen (95% sensitive). Treatment of cryptococcal meningitis requires intravenous amphotericin B (0.7 mg/kg/day); 5-flucytosine (100 mg/kg/day) may be added to this regimen. Oral fluconazole (400 mg/day) may be used as initial therapy in patients with normal mental status.
Toxoplasma gondii is the most common organism causing focal intracranial mass lesions in patients with HIV infection. The incidence is approximately 3-4%. Common presenting symptoms include headache, fever, altered mental status, focal deficits, and seizures. Serologic testing is not generally helpful, because antibody to T. gondii is widely prevalent in the general population. Diagnosis of toxoplasmosis is most often made by CT findings of multiple subcortical lesions, with ring-enhancement seen on contrast CT. Toxoplasmosis of the brain can be difficult to distinguish from a wide variety of other causes, including lymphoma, cerebral TB, fungi, progressive multifocal leukoencephalopathy, CMV, and Kaposi’s sarcoma (KS).
Patients with suspected toxoplasmosis should be treated as inpatients with pyrimethamine (100-200 mg PO loading dose, followed by 50-100 mg/day PO), plus sulfadiazine (4-8 g/day PO) with folinic acid (10 mg/day PO) to reduce the incidence of pancytopenia. Short courses of high-dose steroids are beneficial in cases in which significant edema or mass effect is noted. Seizure prophylaxis with phenytoin also may be used in these cases.
CNS lymphoma occurs in up to 3% of patients with HIV, typically in those with CD4 cell counts of fewer than 100. The most common clinical finding is a change in mental status. Diagnosis is usually made based on CT findings, where hyperdense or isodense round or multiple enhancing lesions, particularly in the periventricular region, are noted. Prognosis for lymphoma is poor and median survival is less than one month.4
HIV encephalopathy, or AIDS dementia complex, occurs in up to one-third of patients with HIV. It is a progressive process caused by direct HIV infection and is commonly heralded by impairment of recent memory or subtle cognitive deficits, such as difficulty concentrating. Symptoms typically occur in patients with CD4 counts of less than 200 cells/mm3. HIV encephalopathy is a diagnosis of exclusion, and ED evaluation should be done to rule out other CNS processes. HIV encephalopathy may be treated with high-dose zidovudine, in coordination with an infectious disease specialist or neurologist.
Ophthalmologic Manifestations. Ocular findings are common in the HIV-infected patient. Cotton-wool spots in the retina are the most common eye finding in AIDS patients and do not require intervention.
CMV retinitis is the most common cause of blindness in AIDS patients, and occurs in 10-30% of patients. CMV retinitis typically produces severe necrotic vasculitis and retinitis. Clinical symptoms may include blurred vision, change in visual acuity, floaters, flashes of light, photophobia, scotoma, redness, or pain.5 It is diagnosed by its characteristic appearance on ophthalmoscopy of fluffy white retinal lesions, often perivascular. Differential diagnosis includes toxoplasmosis, syphilis, HSV infection, VZV (varicella zoster virus) infection, and tuberculosis. Treatment should be initiated with ganciclovir, 5 mg/kg every 12 hours for two weeks, followed by 6 mg/kg/day maintenance therapy. Other therapies may include foscarnet, intravitreal injections of fomivirsen, and ganciclovir-containing intravitreal implants.
Pulmonary Complications. Pulmonary manifestations of HIV are among the most common reasons for ED visits among AIDS patients. The differential diagnosis of respiratory involvement is broad and includes such etiologies as bacterial infections (Streptococcus pneumoniae, Haemophilus influenzae, Chlamydia pneumoniae, etc.), protozoal infections (Pneumocystis jiroveci, Toxoplasma gondii, etc.), viral infections (CMV, adenovirus, etc.), fungal infections (C. neoformans, Histoplasma capsulatum, Aspergillus fumigatus, etc.), malignancies (KS, carcinoma, lymphoma, etc.), and others (lymphocytic interstitial pneumonitis, pulmonary hypertension, etc). Presenting symptoms are often nonspecific and may include cough, dyspnea, fever, or hemoptysis.
Diagnostic evaluation of patients with pulmonary complaints may include chest radiography, CBC, and arterial blood gas (ABG) analysis. Other tests may be indicated in certain situations, such as serum lactic dehydrogenase (LDH), sputum culture, blood culture, Gram’s stain, and special stains (Gomori, Giemsa, acid-fast).
Pneumocystis pneumonia (PCP) is one of the most common opportunistic infections in AIDS. More than 80% of AIDS patient’s acquire PCP at some time during their illness, and it is the initial opportunistic infection in many cases. PCP is caused by the organism P. jiroveci, formerly referred to as P. carinii.6 It is still acceptable to use the acronymn PCP, in reference to Pneumocystis pneumonia. The chest radiograph commonly shows a diffuse interstitial infiltrate, but may also reveal normal findings, asymmetry, nodules, cavitation, or bullae. Other diagnostic tests include gallium scanning of the chest, bronchoscopy (bronchoalveolar lavage, brush biopsy, transbronchial biopsy), and induced sputum with indirect immunofluorescent staining using monoclonal antibodies.
Establishment of a definitive diagnosis is not necessary prior to the initiation of treatment. Treatment should be initiated as early as possible, with 15-20 mg/kg/day of trimethoprim and 75-100 mg/kg/day of sulfamethoxazole (TMP-SMX), given either orally or IV for a total of 21 days. (a typical adult dose may be two TMP-SMX double-strength tablets every eight hours). Other therapeutic options include pentamidine isethionate, dapsone, or other agents. In addition, steroid treatment (prednisone, 40 mg, PO, twice daily with a tapering dose over three weeks) is recommended for patients with a PaO2 less than 70 mmHg, or an A-a gradient of greater than 35.7
The incidence of Mycobacterium tuberculosis (MTB) in HIV-infected patients has increased dramatically, from a low point reached in 1985. The incidence has increased particularly in socioeconomically disadvantaged groups, including prisoners and IV drug users. HIV-infected patients have an estimated 50- to 200-fold increased risk of acquiring TB compared to the general population.8 Common presenting symptoms include fever, cough, and hemoptysis. Radiographic abnormalities may vary considerably. Extrapulmonary disease is more common among HIV-infected patients, and may occur in up to 75% of cases. Multidrug-resistant tuberculosis is becoming an issue of concern, particularly among the HIV-infected population. Diagnostic testing may include PPD skin testing, sputum stain and culture, or biopsy of affected organs.
AIDS patients with tuberculosis should receive a four-drug regimen for six months with isoniazid, rifampin, pyrazinamide, and either ethambutol hydrochloride or streptomycin.9 Second-line agents may include ciprofloxacin, ofloxacin, kanamycin, and other agents.
Fungal pulmonary infections may be seen in AIDS patients. Etiologies may include cryptococcosis, aspergillosis, histoplasmosis, coccidioidomycosis, nocardiosis, and blastomycosis.10 Viral infections also occur in HIV-infected patients. CMV is the most common viral pulmonary pathogen, and typically occurs in advanced immunosuppression. Pulmonary malignancies are also a diagnostic possibility. KS typically is associated with hilar peribronchovascular thickening, lower lobe reticulonodular opacities, adenopathy, pleural effusion, or focal consolidation. Other malignancies, including non-Hodgkin’s lymphoma, Hodgkin’s disease, and bronchogenic carcinoma may be seen. Lymphoproliferative disorders may include lymphocytic interstitial pneumonia (LIP), nonspecific interstitial pneumonia (NSIP), and bronchiolitis obliterans.
Cardiovascular Manifestations. While autopsy findings suggest cardiac involvement in up to 73% of deceased AIDS patients, clinically significant cardiac disease in the AIDS patient is relatively uncommon.11 Cardiac findings may include pericardial effusion, cardiomyopathy, increased left ventricular mass, myocarditis, endocarditis, malignancy, and cardiotoxicity of medications.12 The pericardium is the most common site of cardiac involvement, although most patients have clinically insignificant effusions. Pericardial effusions may be secondary to malignancies, uremia, lymphatic obstruction, or infections. Cardiomyopathies may occur secondary to primary HIV infection, viral, mycobacterial, fungal or protozoal infection, drug-induced, immunologic, or ischemic. Infective endocarditis occurs commonly in HIV-infected patients with a history of injecting drug use. Cardiac neoplasms may also occur, typically either KS or lymphoma.
Gastrointestinal Involvement. The most common GI symptoms are diarrhea, weight loss, malabsorption, abdominal pain, bleeding, esophageal symptoms, and hepatobiliary symptoms. Nonspecific symptoms of nausea, vomiting, and abdominal pain are common adverse effects of antiretroviral therapy. Treatment in the ED focuses on supportive care, fluid and electrolyte repletion, and obtaining of appropriate studies for further investigation.
Oral involvement is common, and may include etiologies such as fungal infections (oral candidiasis, histoplasmosis, cryptococcosis, penicillinosis), viral lesions (herpes simplex, herpes zoster, cytomegalovirus, hairy leukoplakia, papillomavirus), bacterial lesions (periodontal disease, necrotizing stomatitis, tuberculosis, mycobacterium avium complex [MAC], bacillary angiomatosis), neoplasms (KS, lymphoma, Hodgkin’s lymphoma), and autoimmune or idiopathic lesions (salivary gland disease, aphthous ulcers, etc.).
Oral candidiasis affects more than 80% of AIDS patients. Candida albicans, the most common fungal infection in HIV-infected patients, typically involves the tongue and buccal mucosa, and may be asymptomatic. Symptoms may include soreness, burning, and dysphagia. Candidiasis may be described as whitish lacy plaques, which are easily scraped away from an erythematous base. Microscopic examination of the material on potassium hydroxide smear can confirm the diagnosis. Clotrimazole troches (10 mg, PO, five times daily for 14 days) are the preferred treatment for oral candidiasis. Other treatment options include nystatin vaginal tablets, which may be dissolved slowly in the mouth four times daily, or nystatin pastilles (two pastilles dissolved in the mouth five times daily). Systemic therapy may be used for resistant lesions, such as ketoconazole, fluconazole, or itraconazole.
Complaints of dysphagia, odynophagia, or chest pain may be indicative of esophageal involvement. Candida, HSV, and CMV infection all may cause painful esophagitis. Other etiologies may include KS, Mycobacterium avium complex, reflux esophagitis or idiopathic. The most cost-effective approach to the evaluation of patients with esophageal complaints is to initiate empiric therapy with oral antifungal agents for two weeks, and proceed with endoscopy for patients who fail to improve after two weeks.
Diarrhea is the most common gastrointestinal complaint in AIDS patients and is estimated to occur in 50-90% of patients. Diarrhea can be significant and may lead to massive fluid loss with dehydration, fever, chills, and weight loss. Medication side effects should be considered, as antiretroviral agents have a high incidence of gastrointestinal adverse effects. Potential pathogens causing diarrhea include parasites (Cryptosporidium parvum, Isospora belli, Giardia lamblia, Entameba histolytica, and others), bacteria (Salmonella, Shigella, Campylobacter, Helicobacter pylori, Clostridium difficile, and others), viruses (CMV, herpes simplex, HIV, and others), and fungi (Histoplasma capsulatum, C. neoformans, and others).
Cryptosporidium and Isospora infections are commonly associated with HIV infection, and both organisms may produce prolonged watery diarrhea.13 Diagnosis may be sought using acid-fast staining of stool samples, or by monoclonal antibody, or enzyme-linked immunoabsorbent assays. Symptoms may be treated with diet modification and/or loperamide. Cryptosporidium infections may be treated with some success with paromomycin (500-750 mg, PO, four times daily for 2-4 weeks), or azithromycin (2400 mg/day on day 1, followed by 1200 mg/day for four weeks, followed by 600 mg/day). Isospora infections often are successfully treated with TMP-SMX (one DS tablet, PO, three times daily for 10 days, followed by twice weekly therapy for three weeks).
Renal Manifestations of HIV Infection. Renal insufficiency in the AIDS patient may occur due to numeous etiologies. Prerenal azotemia is the most common renal abnormality, especially in conjunction with volume loss related to systemic or gastrointestinal infection. It is diagnosed and treated by evaluation and therapy of fluid status. Acute renal failure may also occur and is often secondary to drug nephrotoxicity (e.g., pentamidine, aminoglycosides, sulfa drugs, foscarnet, rifampin, dapsone, and amphotericin B). HIV-associated nephropathy (HIVAN) is typically a cause of chronic renal insufficiency in the late stages of immunosuppression, but may occur earlier in disease progression.14 Vasculitis, tuberculosis, or other systemic infections may also contribute to renal insufficiency. Post-renal azotemia may result from tubular, ureteral, or pelvis obstruction, from lymphoma, stones, fungus ball, blood clot, or sloughed papilla.
ED evaluation should include urinalysis, assessment of fluid status, blood urea nitrogen (BUN), and creatinine. If indicated, ultrasound or intravenous pyelogram (IVP) may demonstrate the site and degree of obstruction. Renal biopsy may ultimately be required for patients with proteinuria and undiagnosed renal disease. Treatment depends on the causative agent. Therapies, which have demonstrated limited benefit for HIVAN include corticosteroids, angiotensin-converting enzyme (ACE) inhibitors, and dialysis.
Sexually Transmitted Diseases. Sexually transmitted diseases are commonly seen in HIV infected patients. In addition to testing for the more common entities (e.g., gonorrhea, Chlamydia, and herpes infections), serologic testing for syphilis should be performed for all patients presenting with symptoms suggestive of possible sexually transmitted disease. Syphilis has been associated with increased susceptibility to HIV seroconversion.15 The prevalence of syphilis in the United States recently has increased.16
Dermatologic Disorders. Several common cutaneous manifestations of AIDS likely are to be seen in the ED. Any preexisting dermatologic conditions may be exacerbated by HIV infection. Common infections and conditions may present in an atypical fashion. Generalized cutaneous complaints such as xerosis (dry skin) and pruritus are common and may be manifested before any AIDS-defining illness.
KS is the second most common manifestation of AIDS and has involved approximately 25% of the known cases to date. The disease usually is disseminated widely with mucous membrane involvement, although it rarely is primarily fatal. KS typically presents in HIV-infected patients with any variation of mucocutaneous involvement, lymph node involvement, or involvement of the gastrointestinal (GI) tract or other organs. The typical appearance of cutaneous involvement is pink, red, or purple papules, plaques, nodules, and tumors. Treatments available include cryotherapy, radiotherapy, intralesional or systemic chemotherapy.17
Varicella zoster eruptions involving several dermatomes are commonly seen in patients with AIDS. In the HIV-infected patient with simple dermatomal zoster infection, outpatient management should be initiated with oral famciclovir (5 mg, PO, bid or tid, for seven days), acyclovir (800 mg, five times daily), or valaciclovir (1000 mg, bid for seven days). Admission is warranted in any patient with systemic involvement, ophthalmic zoster, or severe dermatomal zoster.
Herpes simplex (HSV) infections are very prevalent among HIV-infected patients. Both HSV-1 and HSV-2 may be seen as local infection and systemic involvement. HSV infections commonly present with fever, adenopathy, malaise, and ulcerative lesions of mucosal and cutaneous sites. Common sites of involvement include oral mucosa, genital areas, and rectum. Oral famciclovir (750 mg, PO, three times daily) or acyclovir, famciclovir, penciclovir, foscarnet, or valaciclovir is recommended.
Scabies should be considered in all HIV-infected patients, particularly those with dermatitis with excoriations, or pruritus. Preferred treatment is with 5% permethrin. Sexual and household contacts also should be treated. Norwegian scabies is a variant seen in HIV-infected patients, and is particularly difficult to eradicate.
Psychiatric Presentations. The diagnosis of AIDS involves complex psychologic and social issues, in addition to physiologic, neurologic, and psychiatric abnormalities. Interactions with family and friends may be changed dramatically, and issues of confronting chronic illness and death may prove devastating.
Depression is common among AIDS patients and often is responsive to hospitalization and psychosocial intervention. It has been estimated that 60% of HIV-infected patients experience depression during their illness.18 Patients with a history of depression are at increased risk. Depression may result in suicidal ideation and may bring the patient to the attention of the ED after a suicide attempt, such as a drug overdose. Antidepressant therapy may be considered if symptoms of depression continue longer than two weeks. Other psychiatric disorders may be seen, including personality disorders, addiction disorders, and adjustment disorders.
AIDS psychosis commonly presents with psychiatric symptoms such as hallucinations, delusions, or other abnormal behavioral changes. Treatment should be undertaken with traditional antipsychotic agents.
Hematologic Complications. Common hematologic complications may include anemia (present in up to 80% of patients), neutropenia, and thrombocytopenia. Hematopoieses may be adversely affected by HIV itself, tumor, infection, or medications.19 Coagulation disorders may be seen, secondary to lupus anticoagulant, viral infections, or idiopathic etiologies.
Drug Reactions. Drug reactions are extremely common among HIV-infected patients for two reasons: First, they are commonly treated with a variety of drugs known to produce adverse effects in some individuals, and second, for unclear reasons, HIV-infected individuals often have more frequent or more severe reactions to commonly used medications. Dermatologic reactions particularly are common. Gastrointestinal effects, such as nausea, vomiting, and diarrhea also are common reactions to many agents. Antimicrobial drugs most commonly are implicated. Potential drug interactions always should be considered when prescribing new medications. Drug reactions should always be considered as a possible cause of new symptoms. Reactions are numerous and current references should be consulted when drug reactions are suspected.
Antiretroviral Therapy. The introduction of highly active antiretroviral therapy (HAART) in 1996 has had dramatic effects on the clinical consequences of HIV infection in the developed world. The incidence of AIDS defining illnesses and death rate have declined significantly.20 In 2003 the Department of Health and Human Services (DHHS) published updated guidelines for use of antiretroviral agents in HIV-infected adults and adolescents.21 In general, multiple goals of antiretroviral therapy include virologic, immunologic, clinical, and therapeutic goals. The principal clinical goals of therapy are to prolong and improve quality of life.
There are three basic classes of antiretroviral drugs. These include the nucleoside analog reverse transcriptase inhibitors (NRTIs), the nonnucleoside reverse transcriptase inhibitors (NNRTIs), and the protease inhibitors (PIs) . Each group of drugs independently interrupts the normal life cycle of the HIV.
The NRTIs are a group of drugs which are competitive inhibitors of the viral enzyme reverse transcriptase. Several controlled trials showed zidovudine (Azidothymidine, AZT, Retrovir) decreases the number and severity of opportunistic infections.22 The most common side effects of these agents include bone marrow suppression and distal sensory peripheral neuropathy.
The NNRTIs are noncompetitive inhibitors of reverse transcriptase and block RNA-dependent and deoxyribonucleic acid (DNA)-dependent DNA polymerase activity. The most commonly used are nevirapine (Viramune) and efavirenz (Sustiva). Target organisms have a high propensity for developing resistance to these agents, which are recommended for use only as part of a three-drug (or more) regimen. Rash is the most common side effect associated with the NNRTIs.23
Protease inhibitors block the enzyme HIV protease, which activates the HIV proteins, which are required for infectivity. However, PIs are expensive and they also have been associated with a high frequency of side effects. Short-term effects are principally GI (including nausea, diarrhea, and bloating); long-term effects are metabolic, such as hyperglycemia, hyperlipidemia, and fat redistribution.24
Most experts recommend treatment for any patient with either a CD4 count of fewer than 350 cells/mm3 or an HIV viral load of greater than 55,000 copies/mL. The recommendation to treat asymptomatic patients should be individualized based on the potential benefits and risks of initiating therapy in an asymptomatic person.
Selection of an appropriate combination of drugs is also a complex issue for which no definitive recommendations currently exist. Twenty antiretroviral drugs currently are approved by the FDA. An up-to-date guide for their use can be found on the NIH web site.25
Precautions and Post-Exposure Prophylaxis
Precautions/Exposures. Health care workers are often exposed to the blood and body secretions of patients who are at high risk of harboring HIV and other infectious pathogens. The overall risk of having any occupational blood exposure is significant, with more than half of emergency physicians reporting at least one occupational exposure during a two-year period.26 However, the overall risk of contracting HIV through occupational exposures remains small. The estimated risk of HIV transmission is estimated at 0.3% via percutaneous exposure and 0.09% for mucocutaneous exposure.27
HIV transmission by health care workers to patients appears to be extremely rare. There have been only seven cases to date, six of which occurred from a single dentist’s practice, and one from a patient who apparently acquired HIV during orthopedic surgery. At this time, routine screening of health care workers is not indicated.28
Numerous studies have demonstrated that health care workers can significantly reduce their risk of exposure to blood-borne pathogens by following universal precautions. CDC guidelines for universal precautions include the use of protective equipment (including gloves, gown, mask, and eye protection) for any situation in which the potential for exposure exists.
Postexposure Prophylaxis. Occupational Exposures. Postexposure prophylaxis (PEP) has demonstrated reduced risk of HIV transmission and seroconversion.29 The CDC provides explicit guidelines for PEP for occupational exposure to HIV. (See Table 2.)30 Current guidelines advise case-by-case determination of the risk of the exposure to determine whether PEP should be recommended. Recommendations are based on two primary factors, type of exposure and HIV status of the source. Higher risk percutaneous exposures include deep injuries, visible blood on a device, and injuries sustained when placing a catheter in a vein or artery; lower risk percutaneous exposures include superficial injuries or solid needles (such as suture needles). High-risk sources include patients with AIDS, acute seroconversion or high viral load.31 When the status of the source is not known (i.e., no recent positive or negative serology), rapid testing should be performed, using a rapid test such as SUDS or OraQuick. Some states allow testing the source without informed consent. State law should be followed regarding testing of source patients.
Current public health guidelines recommend no PEP for HIV-negative sources, and a four-week regimen of two drugs for most HIV exposures via percutaneous or mucus membrane routes.32 Two-drug therapy options include either zidovudine and lamivudine (first choice), lamivudine and stavudine, or didanosine and stavudine. For highest risk exposures, a three-drug regimen with the addition of either a protease inhibitor (e.g., indinavir or nelfinavir), a NNRTI (e.g. efavirenz), or a NRTI (e.g., abacavir) is advised. PEP should be initiated as soon as possible after the exposure to source person with known HIV infection, and should be continued for four weeks. Current guidelines suggest starting treatment within 1-2 hours and generally restrict therapy to those who seek treatment within 36 hours of exposure. Initial treatment should never be delayed while awaiting information regarding final determination of overall risk of exposure, as therapy can be stopped after the first dose. In addition to evaluation and management of HIV exposure risk, all patients should be tested and treated for other more highly infectious agents such as hepatitis. Institutions should maintain policies regarding occupational exposures and postexposure prophylaxis.
Nonoccupational Exposure. Because the risk of HIV transmission by certain sexual or injection drug exposures is relatively high, PEP for nonoccupational exposures also should be considered. The CDC has not yet issued guidelines for nonoccupational PEP citing the lack of data regarding the efficacy of this therapy in those populations.
Patient populations that may seek nonoccupational PEP include sexual assault victims, police, EMS personnel, sexual partners or needle-sharing partners of sources with known or suspected HIV infection.
As with occupational exposures, PEP should be considered on a case-by-case basis.33 A thorough history should be taken to assess the risk of the source, risk of the exposure and the risk for ongoing high-risk exposures. Baseline HIV testing of the exposed patient and the source (when possible) should be performed. Patients should be informed regarding the lack of definitive data for nonoccupational PEP.34 Counseling should be provided regarding medication side effects, which carefully should be considered and balanced with advantages of therapy. All sexual assault victims should be counseled regarding risk/benefits of PEP treatment.
Local infectious disease consultants often should be involved in PEP decisions. Other invaluable resource for information on both occupational and nonoccupational exposures include the CDC/UCSF National Clinicians PEP Hotline, providing a 24-hour assistance (1-888-448-4911) and University of California—Los Angeles’s on-line decision making support at www.needlestick.mednet.ucla.edu.
Consultations with an infectious disease specialist, neurologist, psychiatrist, AIDS specialist, and others may be indicated. Disposition decisions for HIV-infected patients are based on clinical condition, availability of outpatient resources, and ability to arrange adequate follow-up observation. Any patient to be discharged must demonstrate ability to care for himself or herself or to be cared for, and to tolerate sufficient oral intake.
1. Centers for Disease Control and Prevention. 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR Morb Mort Wkly Rep 1993;41(RR-17):1.
2. Joint United Nations Programme on HIV/AIDS. AIDS epidemic update: 2003. Available at www.unaids.org. Accessed Dec. 11, 2003.
3. Centers for Disease Control and Prevention: HIV/AIDS Surveillance Report. Available at www.cdc.gov/hiv/stats/hasrlink.htm. Accessed Dec. 11, 2003.
4. Sackoff J, McFarland J, Su S, et al. Prophylaxis for opportunistic infections among HIV-infected patients receiving medical care. J Acquir Immune Defic Syndr Hum Retrovirol 1998;19:387.
5. Wei LL, Park SS, Skiest DJ. Prevalence of visual symptoms among patients with newly diagnosed cytomegalovirus retinitis. Retina 2002;22:278-282.
6. Stringer JR, Beard CB, Miller RF, et al. A new name (Pneumocystis jiroveci) for Pneumocystis from humans. Emerg Infect Dis 2002;8:891-896.
7. NIH-UC Expert Panel for Corticosteroids as Adjunctive Therapy for Pneumocystis Pneumonia: Consensus statement for use of corticosteroids as adjunctive therapy for Pneumocystis pneumonia in AIDS. N Engl J Med 1990;323:1500.
8. Markowitz N, Hansen NI, Hopewell PC, et al. Incidence of tuberculosis in the United States among HIV-infected persons: The pulmonary complications of HIV infection study group. Ann Intern Med 1997;126:123-132.
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Physician CME Questions
1. Which of the following is true regarding therapy of PCP pneumonia?
A. Definitive diagnosis should be made prior to initiation of therapy.
B. Pentamidine is appropriate first-line therapy.
C. Steroids should be prescribed for patients with PaO2 less than 70 mmHg.
D. All patients with suspected PCP pneumonia should be admitted.
2. Which of the following organisms is the most common etiology of focal intracranial mass lesions among AIDS patients?
A. Cryptococcus neoformans
B. Mycobacterium tuberculosis
C. CNS lymphoma
D. Toxoplasma gondii
3. Which of the following organisms is the most common etiology of blindness in AIDS patients?
A. Cryptococcus neoformans
B. Mycobacterium tuberculosis
C. Pseudomonas aeruginosa
D. Toxoplasma gondii
4. Which of the following is the most appropriate postexposure prophylaxis regimen following a deep needlestick injury following an arterial stick in an HIV positive patient with AIDS?
A. No postexposure prophylaxis indicated
B. Zidovudine alone
C. Zidovudine plus ddI
D. Zidovudine plus lamivudine
E. Zidovudine plus lamivudine plus indinavir
Answers: 1. C; 2. D; 3. E; 4. E