Definition of Problem

During the past 20 years, rates of pediatric human immunodeficiency virus-1 (HIV) and acquired immunodeficiency syndrome (AIDS) have decreased dramatically. With the advent of life-saving combined antiretroviral therapy (cART), HIV-infected infants, children, and adolescents are less likely to present to the emergency department (ED) with HIV-related disease progression, including opportunistic infection and malignancies. As frontline health care providers, ED physicians should be comfortable with recognizing and diagnosing perinatally acquired HIV in infants and children who were missed in the perinatal period, as well as adolescents who may be newly infected with HIV. Familiarity with antiretroviral medications, their associated toxicities, and clinically relevant drug-drug interactions is useful. Lastly, ED physicians are occasionally called on to provide counseling and prophylaxis medications for children and adolescents exposed to HIV inadvertently through needlesticks, mucous membranes, or sexual abuse.

Epidemiology

HIV may be acquired either vertically or horizontally. Vertical, or perinatal, transmission occurs when the virus is transmitted from mother to child in utero, during labor and delivery, or through breastfeeding. Horizontal transmission occurs when the virus is acquired behaviorally through the exchange of bodily fluids, typically through sexual contact or needle sharing.

In 2010, an estimated 10,798 persons younger than 13 years of age with perinatally acquired HIV were living in the United States, approximately half of whom had progressed to AIDS. Perinatally acquired AIDS cases peaked in 1992 and have decreased by more than 95% in the past two decades, with only 334 new cases between 2008 and 2011.1,2 Of children who are perinatally infected with HIV, most are diagnosed shortly after birth, and the majority are diagnosed within the first 24 months of life.

In contrast to perinatally acquired infections, approximately 39,034 adolescents and young adults aged 13 to 24 were living with HIV in the United States in 2010.1,3 In 2011, there were approximately 2,317 newly acquired cases of HIV in the United States in patients between 13 and 19 years of age. Of these adolescents, 92.8% of the males acquired HIV through males having sex with males (MSM), while 92.7% of the females acquired HIV through heterosexual contact.3

Etiology: Perinatal Transmission

The decrease in perinatal HIV transmission from mother to child is due to a variety of factors, including increased awareness and education, early diagnosis of HIV in pregnant mothers, use of early cART during pregnancy, changes in recommendations for mode of delivery, and recommendations to limit breastfeeding in HIV-positive mothers. With these interventions, the rate of perinatal transmission in non-breastfeeding HIV-infected mothers has dropped from 25-40% to less than 2%.4-10 The majority of perinatal HIV occurs in women who were poorly adherent to their antiretroviral therapy, received inadequate or no prenatal care, or were infected with HIV late in pregnancy.

Etiology: Behaviorally Acquired Cases

U.S. data from 2010 show that among adults with newly acquired HIV, 25% acquired the virus heterosexually, 63% via MSM, and 11% outside of the setting of sexual contact typically through intravenous drug use (IVDU). Adolescents and young adults aged 15-24 are at high risk for acquiring HIV infection due increased risk factors and decreased rates of screening. (See Figure 1.)11

Pathophysiology

After exposure to HIV, CD4 T-cells and Langerhans’ cells in the mucosa serve as an initial site of viral replication.12,13 The virus continues to replicate as the CD4 T-cells migrate to lymphatic tissues throughout the body.13 During this time, there is rapid viral replication, destruction of reservoirs of CD4 T-cells, and establishment of viral latency.13

After the period of acute HIV infection, the amount of HIV-1 viral copies detected in plasma, known as the viral load (VL), stabilizes and then declines to a viral set point. The virus continues to replicate in lymphoid tissues throughout the body, leading to a continued increased rate of turnover of CD4 T-cells.12 In addition to alteration in the numbers of T-cells, the quality of T-cells is affected as well, leading to alteration in immune response and progression of HIV disease.12 Antibodies that neutralize the transmitted virus are usually produced within six weeks of initial infection, but in some infected individuals, they may not be produced for at least three months after initial infection.14 (See Figure 2.)

 

Natural History of HIV in Children

With the advent of antiretroviral therapy in the 1990s and continued advancements during the past two decades, patients with HIV/AIDS in the developed world are now living longer. However, pediatric patients with perinatally acquired HIV still have a mortality rate that is about 30 times higher than the general U.S. pediatric population.15,16

As HIV progresses, CD4 T-lympho-cytes become depleted, leading to lower CD4 percentages and lower CD4/CD8 ratio, resulting in increased risk for opportunistic infection and AIDS.17 Without cART, 15-20% of HIV-infected children die before 4 years of age (rapid progressors), and 80-85% have delayed onset of milder symptoms, surviving beyond 5 years of age (slow progressors).18 In the United States, the most common AIDS-defining illnesses are Pneumocystis jirovecii pneumonia (previously Pneumocystis carinii or PCP), lymphocytic interstitial pneumonitis (LIP), recurrent bacterial infections, wasting syndrome, candida esophagitis, HIV encephalopathy, and cytomegalovirus (CMV) disease.

Per the 2008 CDC guidelines, HIV infection in children is classified clinically (see Table 1) and immunologically.19,20 As of 2014, the CDC revised its classification system for surveillance and based it mainly on CD4 T-lymphocyte counts unless the patient has acute HIV infection (now referred to as stage 0) or a stage 3-defining opportunistic illness. (See Table 2.)

Children and Adolescents with Previously Diagnosed HIV/AIDS

Patients previously diagnosed with HIV/AIDS may or may not be on cART, and compliance is variable. The incidence of opportunistic infections in pediatric patients with HIV/AIDS has dropped since the advent of cART therapy.21 (See Table 3.)

Patients on cART may present with adverse reactions or side effects due to their medications, although current cART is generally well-tolerated. Patients recently initiated on antiretroviral medication may show signs of immune reconstitution inflammatory syndrome (IRIS) (See below: Immune Reconstitution Inflammatory Syndrome). Immunocompromised patients may present with a variety of clinical symptoms, and the differential diagnosis varies based on these presenting complaints and severity of immunosuppression. (See below: Approach to the HIV-infected Patient in the Emergency Department).

Infants and Children with Undiagnosed Perinatally Acquired Infection

For infants and children with undiagnosed perinatally acquired HIV or AIDS, clinical manifestations are often nonspecific. The most common presenting symptoms in the first year of life include lymphadenopathy, unexplained hepatosplenomegaly, oral candidiasis, failure to thrive, and developmental delay. Often, these children and teenagers come to medical attention with recurrent severe or unusual infections. (See Table 1.) Children diagnosed late in their childhood are often cared for by families who were unaware of the child’s biological mother’s HIV diagnosis.

Adolescents with Acute HIV

 

The emergency physician should also consider new diagnoses of HIV in the adolescent or adult who may have acute HIV or acute retroviral syndrome (ARS). The diagnosis of ARS should be in the differential for patients who have a high-risk exposure within the previous 2-6 weeks, and are manifesting one or more of the following symptoms: fever, lymphadenopathy, skin rash, sore throat, myalgias, arthralgias, headache, diarrhea, oral ulcers, leukopenia, thrombocytopenia, transaminase elevation, or aseptic meningitis.22-24 (See Table 4.) High-risk exposures include sexual contact with a person with known HIV or at risk for HIV, multiple sexual partners, MSM, exchanging sex for money or drugs, IVDU, and being the sexual partner of an intravenous drug user or someone diagnosed with a new sexually transmitted infection (STI).23 The other considerations on the differential for these patients include Epstein-Barr virus (EBV) and CMV-related infectious mononucleosis, influenza, viral hepatitis, streptococcal infection, and syphilis.

During this one- to four-week period after HIV infection, the antibodies to the virus may not be detectable in plasma, and HIV screening tests designed to detect HIV antibodies may be negative.13 (See section: Diagnostic Studies in HIV and AIDS.) During this time, the patient is highly infectious, as the virus is replicating aggressively and the viral load is high.25,26

The emergency physician has three responsibilities in cases of acute HIV.13 First, the ED physician should conduct appropriate testing. Second, there should be counseling for patients with potential acute HIV to prevent continued transmission of the virus and reporting of the infection to the department of health. Third, the ED physician should ensure appropriate outpatient follow up for the patient.

Initiation of antiretroviral medications is typically not an emergency, and requires expert consultation. A clinician may need to start antiretroviral medications in the ED in cases involving post-exposure prophylaxis within 72 hours of exposure to HIV and for prevention of perinatal transmission in pregnant HIV-infected adolescents. In both of these cases, it is prudent to involve experts in the field and hospital protocols to assist with initiation of antiretroviral therapy.

 

Diagnostic Studies in HIV and AIDS

The appropriate diagnostic studies in patients with suspected or known HIV/AIDS vary depending upon the age of the patient and suspected length of time that the patient has been infected.

Infants Younger than 18 Months of Age. In patients who are younger than 18 months old in whom HIV is suspected, virological testing is recommended.27,28 Virological testing consists of nucleic acid amplification testing (NAAT) using polymerase chain reaction (PCR) to detect HIV-1 DNA or RNA in serum. Qualitative HIV-1 DNA PCR is typically used in diagnosis, while quantitative HIV-1 RNA PCR assays, also referred to as the viral load (VL), are used for monitoring. Antibody testing is not reliable in this age group due to placental transmission of maternal antibodies. A negative antibody test in a non-breastfed infant older than 6 months can, however, exclude HIV infection.17 VL may not be useful in this age group because it may be initially undetectable, even in an infected infant, if mother and infant have been on antiretroviral therapy. If PCR testing is positive, the patient requires repeat confirmatory tests and infectious disease (ID) consultation.28

Toddlers Older than 18 Months of Age. In children who are older than 18 months of age and no longer breast-feeding, HIV ELISA antibody testing (first-generation test) is an appropriate screening test. ELISA detects serum IgG antibodies produced against HIV-1 antigens, including p24 (a nucleocapsid protein) and gp 120 and gp 41 (envelope proteins).28 These antibodies persist for life. Antibody testing may be unreliable during the very late stages of HIV infection, during which there is severe immune suppression.17 Any positive HIV-1 ELISA requires confirmatory testing with Western blot assays, which are more specific for HIV-1, and, eventually, virological testing with HIV-1 DNA or RNA PCR.

Older Children and Adolescents. In older children, newly developed rapid combined antibody-antigen tests (fourth-generation tests) may be used for screening point-of-care testing.29 These tests detect both IgG and IgM antibodies and p24 antigen. They may detect HIV p24 antigen during acute infection when antibody formation is not yet detectable. Fourth-generation tests have been shown to have sensitivity and specificity greater than 99%.29 These tests have not yet been shown to be reliable in infants.30 Older second-generation tests detect IgG antibodies, while third-generation tests can detect both IgG and IgM, allowing for earlier detection of HIV antibodies. If positive, patients need an ID consult and confirmatory testing.

Acute HIV. In patients for whom there is concern for acute HIV, HIV-1 DNA PCR or p24 antigen testing is appropriate.13 In this time period immediately after infection, it is too early for antibodies to be present. This is referred to as the "window period," during which the virus is actively replicating, but antibodies cannot be detected. Since fourth-generation HIV tests have combined antibody-antigen testing, they can be useful in detecting acute HIV infection.31

 

Monitoring

HIV-infected individuals can be classified through immunologic staging based on their CD4 count or CD4 percentage. In children, the stage is based primarily on the CD4 T-lymphocyte count. The CD4 count takes precedence over the CD4 T-lymphocyte percentage, and the percentage is considered only if the count is unavailable or missing.32 (See Table 2.) Knowing an HIV patient’s CD4 count and CD4 percentage is useful to determine their risk for opportunistic infection. VL is also used for monitoring response to antiretroviral therapy and disease progression.

Screening

The CDC, USPSTF, and American Academy of Pediatrics (AAP) all support screening of adolescents for HIV. In the ED setting, this can be accomplished with rapid tests for which results are available in 5-40 minutes.17 Rapid oral tests are recommended only for children who are 13 years of age or older.

Approach to the HIV-infected Patient in the Emergency Department

When approaching a known HIV-infected patient in the emergency department, it is crucial to establish the patient’s level of immune compromise. If the patient has CD4 counts or percentages obtained within the previous three months, these numbers can be used to make this determination (see Table 2). If these counts and percentages are not available, the clinician will need a detailed history and physical examination to clinically classify the patient. The clinician should also assess adherence to cART. HIV-infected children and adolescents who have been reliably adherent to their cART therapy likely will not be immunocompromised. Most patients with HIV and AIDS maintain the ability to develop physiologic signs of infection, including localizing symptoms, fever, tachycardia, tachypnea, and hypotension. Profoundly immunocompromised patients, however, may not have the ability to mount a fever or develop localizing symptoms.

Infectious Considerations

As with all patients presenting to the ED with fever or infectious concerns, diagnostic evaluation should begin with a thorough history and physical examination. In patients with a focal source of infection, cultures from that source should be obtained. In patients without a focal source of infection, little evidence exists regarding the most appropriate degree of infectious work-up to pursue. Expert recommendations include obtaining blood cultures for patients with serious focal infections and those who appear toxic or septic. If severe immune compromise is suspected, obtaining aerobic, anaerobic, and fungal cultures should be considered.

While patients with HIV have a higher incidence of viral and fungal infections than the non-HIV-infected population, HIV-infected patients are more likely to develop and present with bacterial infections. The most common infections in HIV-infected patients are similar to those in patients without HIV, including pneumonia, sepsis, and urinary tract infections, even in the cART era. The incidence of opportunistic infections and other related infections have dropped significantly since the use of cART in children.21,33 Patients maintained on cART therapy have an incidence of 3.66 serious bacterial infections per 100 person-years, which is similar to that of non-HIV-infected children.33

In patients with controlled HIV infection, recommendations for empiric antibiotics are similar to those for uninfected children.34 For HIV-infected children with severe disease, neutropenia, or nosocomial infection, broader empiric antibiotics are recommended.34 Patients with HIV have an incidence of neutropenia of 20-34%. This neutropenia is believed to be multifactorial, likely due to both HIV infection and antiretroviral medications. Despite the presence of neutropenia in these patients, it is relatively well-tolerated, and they do not seem to have the same degree of immune compromise as patients who are neutropenic due to oncologic etiologies.35,36 In patients with severe sepsis or septic shock, there are no clear recommendations regarding whether cART therapy should be continued or temporarily discontinued given the risk of drug interactions, hepatic and cardiac toxicities, pancreatitis, and lactic acidosis associated with various antiretroviral medications.37

Respiratory Complaints

When a child with HIV/AIDS and severe immune compromise presents with respiratory complaints, PCP, LIP, and tuberculosis must be high on the differential.

PCP occurs in 40-50% of reported cases of AIDS in children, and is more common in infancy than in older children.38 Perinatally infected patients often present between 2-6 months of age, and PCP is often the first AIDS-defining illness in children.39 Patients present with tachypnea, dyspnea, cough, low-grade fever, and a significant degree of hypoxia that is exacerbated with exertion.38,40 Symptoms worsen over 1-2 weeks prior to presentation. In patients with PCP, chest radiographs typically demonstrate a diffuse interstitial pattern or bilateral opacifications with air bronchograms with "ground-glass" or reticulogranular appearance, but these findings are not always seen.38,39 Diagnosis is made with nasopharyngeal aspirates, broncho-alveolar lavage samples, or induced sputum samples.38 Treatment includes supportive therapy with oxygen, high dose trimethoprim/sulfamethoxazole (TMP/SMX), potentially with the addition of steroids. Due to high mortality, especially in infants, when there is a high index of suspicion, PCP therapy should be initiated promptly, along with treatment for bacterial pneumonia, even when investigations are not immediately available. Pentamidine, dapsone, or atovaquone may be used instead of TMP/SMX if the patient is allergic to, or cannot tolerate, the medication. Steroids should be added, and may be life-saving in patients with severe hypoxia or an elevated alveolar-arterial (A-a) gradient.38,40

Lymphocytic interstitial pneumonitis occurs in 25-40% of children with perinatally acquired HIV.38,39 The presentation is insidious, and is particularly common in patients older than 2 years of age. Patients typically present with a nonproductive cough and mild hypoxemia. Generalized lymphadenopathy, bilateral non-tender parotid swelling, and clubbing are also seen. Labs may reveal hypergammaglobulinemia.39,41 LIP should be considered in children with HIV who have recurrent pneumonias.38 Definitive diagnosis requires a lung biopsy, which demonstrates diffuse lymphocytic infiltration of the pulmonary interstitium.38 The CDC criteria for a presumptive diagnosis of LIP in an HIV-infected child require persistence of diffuse, symmetrical, reticulo-nodular or nodular pulmonary opacification with or without mediastinal adenopathy for at least two months. There should be no identifiable pathogen, and no response to antibiotic therapy.42,43 Treatment of LIP is primarily supportive, but also includes cART therapy and corticosteroids.44

Tuberculosis (TB) must also remain in the differential diagnosis for any immunocompromised patient with respiratory symptoms, although TB may also have extrapulmonary manifestations. There is significant overlap between those affected by HIV/AIDS and those affected by TB. Approximately one-third of the world’s population is infected with tuberculosis, and it remains a leading killer of people who are HIV-infected.45 Antiretroviral therapy use is strongly associated with a reduced risk of tuberculosis among HIV-infected children.46 In the ED, reactivation of LTBI or TB IRIS should remain on the differential for HIV-infected patients with unexplained symptoms (both pulmonary and extrapulmonary), particularly if they have low CD4 counts, high viral loads, have been noncompliant with or recently initiated on cART, come from an area with endemic TB, or were previously incarcerated or homeless.

Neurologic Complaints

Neurologic complaints in children with HIV/AIDS may include headache, seizures, altered mental status, and other unexpected neurologic changes. The two most common opportunistic infections that must be considered are Cryptococcus and Toxoplasmosis.

Cryptococcus neoformans is a ubiquitous encapsulated fungus, and while it is the most common life-threatening fungal infection in HIV-infected adults, it is uncommon in HIV-infected children.47,48 The most common presentation of cryptococcosis in HIV-infected children is cryptococcal meningitis, which is diagnosed through india ink staining or antigen testing on CSF or antigen testing in the blood.49 Patients often have indolent courses and prolonged symptoms prior to presentation. Cryptococcal meningitis is treated with extended antifungal therapy, usually amphotericin B with flucytosine.49,50

Toxoplasma gondii is a single-cell parasite that is found throughout the world.51 It is acquired through ingestion of contaminated food/water or exposure to cat feces.51 While more than 80% of healthy infected patients are unaffected, patients with HIV/AIDS are more likely to develop severe disease due to immunosuppression. The risk of infection rises when CD4 counts fall below 100 cells/uL.51 Toxoplasmosis in patients with HIV/AIDS may be due to a new infection, or reactivation of previously acquired infection. Immunosuppressed patients typically present with fever and encephalitis, characterized by headache, lethargy, impaired coordination, ataxia, dementia, and seizures.51 The incidence of toxoplasmic encephalitis has decreased since the use of cART.52,53 Computed tomography (CT) scans of the brain often reveal multiple ring-enhancing lesions. Definitive diagnosis requires tissue biopsy or detection in body fluids, often in combination with serologic testing, especially to differentiate from central nervous system (CNS) lymphoma.51 Patients with HIV/AIDS and toxoplasmosis should be treated aggressively, as the clinical course may be rapidly fatal.51 Patients with CD4 counts less than 100 should be on TMP/SMX as prophylaxis against toxoplasmosis (and PCP).51

 

Gastrointestinal Complaints

The most common infectious HIV-related gastrointestinal complaint is oropharyngeal or esophageal candidiasis. Patients with esophageal candidiasis may present with odynophagia, dysphagia, retrosternal chest pain, nausea/vomiting, and/or concomitant oropharyngeal candidiasis.34 In severely immunocompromised patients or in those with indwelling central venous catheters, candidemia and disseminated candidiasis become risks. Oral candidiasis can be treated with topical antifungal therapy (nystatin suspension or clotrimazole troches), while esophageal or disseminated fungal infection requires systemic therapy.34

Other Complications

Patients with long-standing HIV or AIDS may also present with a variety of complaints related to the HIV virus itself. Prior to widespread use of cART therapy, HIV-related neurologic dysfunction was a significant source of morbidity and mortality in HIV-infected children.54,55 Classically, patients present with cognitive and motor deficits, as well as structural brain damage. Clinical findings in children consist of seizures, headaches, behavioral changes, microcephaly, motor dysfunction, and loss of developmental milestones.56,57 The most severe manifestation, progressive encephalopathy, is analogous to HIV-associated dementia in adults. Despite these dramatic improvements, HIV-related neurologic changes are still seen in approximately 10% of HIV-infected children and adolescents on neurologic exam and brain imaging.58

HIV-associated malignancies include Kaposi’s sarcoma (KS), non-Hodgkin’s lymphoma, and cervical carcinoma. Approximately 90% of pediatric patients with HIV-associated malignancies have Kaposi’s sarcoma.59 Patients with lower CD4 counts and high viral loads are at higher risk of developing KS.59,60 Kaposi’s sarcoma is a low-grade vascular neoplasm mediated by human herpesvirus-8. Adults with KS typically present with skin findings and generalized lymphadenopathy. Children, on the other hand, typically present without the typical cutaneous findings. Definitive diagnosis requires tissue biopsy.60

 

Immune Reconstitution Inflammatory Syndrome

The incidence of pediatric IRIS is 10-20%. In affected patients, it occurs within 12 months after initiation of antiretroviral therapy, usually within one week to three months of starting cART. Risk factors for IRIS include a high pathogen load and a very low CD4 count when antiretroviral therapy is initiated.61 Patients have acute worsening in clinical condition due to an infectious or inflammatory condition associated with the restoration of their immune system. Clinical deterioration is due to the unmasking of a subclinical opportunistic infection or the recurrence of a previously treated infection. In these patients, the infectious pathogen is typically easily detectable. The most common causes of IRIS are mycobacterial. BCG (Bacillus Calmette–Guérin) reactivation has also been reported.62 In order to diagnose IRIS, the patient should have evidence of immunological response to antiviral therapy, clinical worsening due to an infectious or inflammatory condition temporally related to the initiation of ART, and symptoms that are not explained by noncompliance with ART, adverse drug reaction, treatment failure of an opportunistic infection, or an alternative infection/neoplasm.62 Treatment for IRIS with reactivation of an infection involves antimicrobial treatment as well as supportive care, possibly including anti-inflammatory medications such as nonsteroidal anti-inflammatory medications (NSAIDs) and steroids. While most cases resolve, IRIS may be fatal, especially in younger children.62

 

Medication Adverse Effects and Drug-Drug Interactions

Patients on cART may present with a variety of complaints that are a direct result of their antiretroviral medications. Currently, there are five major categories of medications to control HIV infection. (See Table 5.)

Each of these medications has its own potential side effects and adverse effects, and many interact with other medications used on a regular basis.

In general, with the exception of abacavir, all nucleoside reverse transcriptase inhibitors (NRTIs) require dose adjustment in the setting of renal insufficiency.63 Protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) are cleared via the cytochrome P450 system in the liver. Therefore, these medications must be dose-adjusted in the setting of hepatic injury.64 NRTIs increase a patient’s risk of developing pancreatitis, particularly in the setting of low CD4 counts and for those patients with a history of pancreatitis.65,66 Other potential adverse effects of antiretroviral therapy include bone marrow suppression, lactic acidosis, liver failure, and hypersensitivity reactions. In patients on cART, when clinically indicated, it may be beneficial to obtain a complete blood count with differential, aminotransferase levels, blood urea nitrogen (BUN), serum creatinine, amylase, and lipase to evaluate for medication toxicities.

In addition to medication-specific adverse effects, the clinician should be aware of potential drug-drug interactions. Particular caution should be taken with the use or prescription of antiarrhythmics, ergot medications, various antiepileptic medications, and benzodiazepines. It is prudent to look up each potential drug-drug interaction on websites such as www.drugs.com or the National Institutes of Health (NIH) website.67,68

Additional Aspects to Consider

Reporting. HIV is a reportable disease in the United States. All reporting is confidential and name-based. Each state has specific laws and regulations around reporting. They can be found at the CDC website: www.cdc.gov/hiv/policies/law/states/.

Post-Exposure Prophylaxis (PEP). In general, PEP is recommended for any direct exposure of the vagina, anus, penis, mouth, or broken skin with semen, vaginal fluid, or blood with or without visible injuries, tissue damage, or blood. This includes injuries with exposure to blood from a source either known to be HIV-infected or HIV unknown (for example, sexual abuse, human bites, accidents) and needle-sharing.

Post-exposure prophylaxis has been shown to be most beneficial in the first 72 hours after exposure, and is not recommended outside of this time frame.69 PEP should be continued for four weeks. If the injured patient is HIV positive at baseline or the source patient is found to be HIV negative, PEP may be discontinued. In addition to starting PEP in appropriate scenarios, follow up should include counseling and testing at baseline and six weeks, three months, and six months after exposure. Patients should also be monitored for PEP toxicities (gastrointestinal disturbances, headache, and fatigue), acute retroviral syndrome, and screened for hepatitis B and C, as well as other STIs.

Low-risk Exposure. Extremely low-risk exposures do not require PEP. Examples include exposure to needles or sharps that have not been in contact with an HIV-infected or at-risk person, human bites not involving blood, kissing, oral sex without ejaculation, or blood exposure or oral-to-oral contact without mucosal damage. Urine, nasal secretions, saliva, sweat, and tears not visibly contaminated with blood carry a negligible risk for HIV exposure. Most commonly, ED physicians encounter community-acquired needlestick injuries (CA-NSIs). The risk of HIV transmission with such events is very low and typically PEP is not warranted.70

Occupational Exposure. The average risk for HIV transmission after a percutaneous exposure to HIV-infected blood is approximately 0.3% (95% CI 0.2-0.5%) and after a mucosal membrane exposure approximately 0.09% (95% CI 0.006-0.5%).71 Source patients should be tested for HIV infection with either HIV-1 DNA PCR testing or fourth-generation combined antibody-antigen tests. If the fourth-generation (rapid) test is positive, confirmatory testing must be pursued. If testing of the source patient is delayed for any reason, PEP should be started pending test results.72 A variety of three-drug regimens are appropriate and are given for 28 days. It is prudent to discuss with an occupational health and an ID consultant regarding institution-specific recommendations.

Non-Occupational Exposure. The risk of HIV transmission after non-occupational exposure ranges from 0.005-0.67%, depending on the type of exposure.69 A variety of two-drug and three-drug regimens exist and are given for 28 days. Consultation with an ID expert regarding institution-specific recommendations is advised.

HIV Testing Consent

As of June 2013, all 50 states and the District of Columbia allow minors to consent to STI services. Of these, 31 states specifically include HIV testing and treatment within the category of STI services. State-specific laws exist regarding verbal and written consent for HIV testing, as well as pre- and post-test counseling. State-specific laws can be found at the CDC website: www.cdc.gov/hiv/policies/law/states/.

Disposition

The ID team should be consulted for any new diagnosis, new opportunistic infection diagnosis, and medication complication or side effect to establish follow up. Antiretroviral therapy should not be discontinued without specific recommendations from an ID or HIV expert.

Summary

Although there has been a decline in pediatric patients with HIV presenting to the emergency department, it remains a complex condition. Fewer patients are presenting with opportunistic infections, but these infections still occur in those who are severely immunocompromised. Additionally, the ED physician should remain alert to recognize patients with undiagnosed perinatal HIV infection, acute retroviral syndrome, and complications of antiretroviral therapy. In general, most pediatric patients with HIV can be approached using the typical emergency department algorithms. Patients with severe immune compromise or advanced HIV/AIDS require consideration of a broader differential diagnosis and lower threshold for diagnostic testing and treatment.

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