TABLE IV-114 Risk Factors for Active Tuberculosis Among Persons Who Have Been Infected With Tubercle Bacilli 3 page
IV-152. The answer is D. (Chap. 186) This patient presents with symptoms of the common cold with a self-limited illness characterized by rhinorrhea and sore throat. The most common viruses causing the common cold are rhinoviruses, which are implicated in as many as 50% of common colds. Rhinoviruses are small single-stranded RNA viruses of the Picornaviridae family. There are three genetic species of rhinoviruses with 102 serotypes identified. Rhinoviruses grow preferentially at the temperature of the nasal passages (33° to 34°C) rather than the temperature of the lower airways (37°C). Although rhinovirus infections occur year round, there are seasonal peaks of the infection in the early fall and spring in temperate climates. Overall, the rates of rhinovirus infection are highest in infants and young children and decrease with age. The virus is most often introduced into families through young children in preschool or grade school. After the index infection, secondary infections occur in other family members 25% to 70% of the time. Rhinovirus spreads through direct contact with infected secretions, which can occur through respiratory droplets or hand-to-hand contact. It can also be transmitted through large or small particle aerosols. Finally, the virus can be isolated from plastic surfaces from 1 to 3 hours after inoculation, raising the possibility that the virus can also be transmitted through environmental contact.
IV-153. The answer is C. (Chap. 186) Acute viral respiratory illnesses are the most common illness worldwide, and a wide variety of viruses have been implicated as causes. Rhinoviruses are the most common virus causing the common cold and are found in about 50% of cases. The second most commonly isolated viruses are coronaviruses. These viruses are more common in the late fall, winter, and early spring, primarily at times when rhinoviruses are less active. Other causes of common cold in children are adenoviruses, whereas these viruses are uncommon in adults with the exception of outbreaks in individuals living in close quarters such as military recruits. Although human respiratory syncytial virus characteristically causes pneumonia and bronchiolitis in young children, the virus can cause common cold and pharyngitis in adults. Parainfluenza virus is another virus classically associated with croup in children, but it causes common cold in adults. Enteroviruses most often cause an undifferentiated febrile illness.
IV-154. The answer is A. (Chap. 186) The common viruses causing respiratory infections often have specific associated clinical syndromes. Rhinoviruses are primarily responsible for the common cold. Coronaviruses are also commonly associated with colds. However, in 2002 to 2003, there was an outbreak of a coronavirus-associated illness that originated in China and spread to 28 countries in Asia, Europe, and North and South America. This illness was named severe acute respiratory syndrome (SARS) and caused severe lower respiratory illness and acute respiratory distress syndrome. Overall, the case-fatality rate was 9.5%. Human respiratory syncytial virus is the primary agent responsible for lower respiratory disease and bronchiolitis in infants and young children. Another virus primarily associated with childhood illness is parainfluenza virus. This virus is a frequent cause of croup in young children characterized by a febrile illness with a barking cough and stridor. Adenovirus often causes a febrile illness with the common cold and pharyngitis in children. In adults, it is associated with outbreaks of respiratory illness in military recruits. Herpes simplex virus is associated gingivostomatitis in children and pharyngotonsillitis in adults.
IV-155. The answer is C. (Chap. 186) In infants, human respiratory syncytial virus (HRSV) is frequently associated with lower respiratory infections in 25% to 40% of infections. This can present as pneumonia, tracheobronchitis, or bronchiolitis. In cases of lower respiratory infections, tachypnea, wheezing, and hypoxemia are common and can progress to respiratory failure. Treatment is primarily supportive with hydration, suctioning of secretions, and administration of humidified oxygen. Bronchodilators are also used to treat wheezing and bronchospasm. In more severe cases, aerosolized ribavirin has been demonstrated to modestly improve the time to resolution of respiratory illness. The American Academy of Pediatrics states that aerosolized ribavirin may be considered in infants who are seriously ill or who are at high risk of complications, including bronchopulmonary dysplasia and congenital heart disease and those who are immunosuppressed. However, no benefit has been demonstrated with use of standard intravenous immunoglobulin or HRSV-specific immunoglobulin.
IV-156. The answer is E. (Chap. 187) Pandemic strains of influenza emerge through genetic reassortment of RNA segments between viruses that affect different species, including humans, swine, and birds. This process is also called antigenic shift during which a new strain of influenza emerges to which very few people have immunity. Antigenic shift only occurs with influenza A because it is the only influenza that crosses between species. Antigenic drift is the result of point mutations in the hemagglutinin or neuramidase proteins. Antigenic drift occurs frequently and is responsible for the interpandemic influenza outbreaks.
IV-157. The answer is A. (Chap. 187, www.cdc.gov/flu) This patient is presenting with an influenzalike illness during the typical flu season. Hospital infection control practices in this setting are to treat all patients presenting with an influenza-like illness as if they have influenza until proven otherwise. This includes institution of droplet precautions to prevent spread to other individuals as well as performing testing to confirm influenza diagnosis. This is most commonly done via a nasopharyngeal swab but can also be done on throat swab, sputum, nasotracheal aspirates, or bronchoscopic specimens if available. If influenza diagnosis is confirmed, assessment of close household contacts for individuals who may be candidates for chemoprophylaxis against influenza is important, particularly individuals who would be high risk of complications from influenza infection. This group includes children younger than 4 years old, pregnant women, individuals age 65 years or older, individuals with heart or lung disease, individuals with abnormal immune systems, and individuals with chronic metabolic diseases
or renal disease.
As far as treatment is concerned, clearly, oxygen should be given to individuals who are hypoxemic. Other appropriate supportive care should also be administered, including intravenous fluids and respiratory therapy support to manage secretions. In general, treatment with antiviral medications has been demonstrated to decrease the duration of symptoms by 1 to 1.5 days when initiated within the first 48 hours after the onset of symptoms. However, the Centers for Disease Control and Prevention (CDC) recommends treatment with antiviral medications as early as possible in patients hospitalized with severe pneumonia. Some evidence indicates that use of antiviral therapy might be effective in decreasing morbidity and mortality in individuals who are hospitalized with severe pneumonia even when given more than 48 hours after the onset of symptoms. The preferred class of antiviral therapy is the neuraminidase inhibitors, which have efficacy against both influenza A and B. In addition, resistance is much lower among this class of medications. This class includes the drugs zanamivir, oseltamivir, and peramivir. Of these, oseltamivir is most commonly used because it is an oral medication with limited side effects. Zanamivir is given by inhalation and can cause bronchoconstriction in individuals with asthma. Peramivir is currently an investigational medication that is administered intravenously.
The adamantine agents include amantadine and rimantadine. These medications have no efficacy against influenza B and also have a high degree of antiviral resistance (>90%) in North America to H3N2 strains of influenza A. It is important to know the resistance patterns to antiviral agents during the local flu season. The CDC currently does not recommend amantadine as first-line therapy for severe influenza. Antibacterial therapy should be reserved for individuals with suspected bacterial complications of influenza.
IV-158. The answer is A. (Chap. 187, www.cdc.gov/flu) The intranasal influenza vaccine contains a cold-adapted, live-attenuated influenza virus. Because of this, its use is more limited than intramuscular inactivated influenza vaccine. It is currently only recommended for healthy individuals between the ages of 2 and 49 years. Contraindications to the use of the live-attenuated intranasal influenza vaccine include pregnancy, chronic pulmonary or cardiovascular conditions, immunosuppressed patients, individuals with a history of Guillain-Barré syndrome, and individuals with a history of severe egg allergy. In addition, individuals who regularly are in contact with immunosuppressed people should not receive the intranasal vaccine, or if it is given, they should avoid contact with severely immunosuppressed patients for 7 days after receipt of the vaccine. In young children, a history of asthma precludes the use of intranasal influenza vaccination because the vaccine can precipitate episodes of wheezing. The Centers for Disease Control and Prevention recommends avoiding the use of the live-attenuated vaccine in individuals whose parents report an episode of wheezing within the past 12 months regardless of whether asthma is a chronic diagnosis. A final caveat in the use of the live-attenuated intranasal influenza vaccine is its use in individuals who are actively taking antiviral medications as chemoprophylaxis against influenza because antiviral medications interfere with the immune response to the live-attenuated influenza vaccine. The current recommendations are that live-attenuated influenza vaccination not be administered for 48 hours after antiviral medications have been stopped and that antiviral medications not be given for 2 weeks after receipt of the live-attenuated influenza vaccine. However, the immune response to the intramuscular inactivated vaccine is not affected by coadministration with antiviral drugs.
IV-159. The answer is D. (Chap. 187) The majority of influenza infections are clinically mild and self-
limited. Treatment with over-the-counter cough suppressants and analgesics such as acetaminophen is often adequate. Patients who are younger than the age of 18 years are at risk of developing Reye’s syndrome if they are exposed to salicylates such as aspirin. The neuraminidase inhibitors oseltamivir and zanamivir have activity against influenza A and B. They can be used within 2 days of symptom onset and have been shown to reduce the duration of symptoms by 1 or 2 days. This patient has had symptoms for more than 48 hours, so neither drug is likely to be effective. The patient’s history of asthma is an additional contraindication to zanamivir because this drug can precipitate bronchospasm. The M2 inhibitors amantadine and rimantadine have activity against influenza A only. However, since 2005, more than 90% of A/H3N2 viral isolates demonstrated resistance to amantadine, and these drugs are no longer recommended for use in influenza A.
IV-160. The answer is C. (Chap. 188) Human T-cell lymphotropic virus-I (HTLV-I) is a retrovirus that is a chronic infection like HIV, but it does not cause similar sequelae. It was the first identified human retrovirus. Gradual decline of CD4+ lymphocyte number and function is a feature of HIV but not of HTLV-I. Although many people in endemic areas have serologic evidence of infection, most do not develop disease. The two major complications of HTLV- I are tropical spastic paraparesis and acute T-cell leukemia. Tropical spastic paraparesis is an upper motor neuron disease of insidious onset leading to weakness, lower extremity stiffness, urinary incontinence, and eventually a thoracic myelopathy, leading to a bedridden state in about one-third of patients after 10 years. It is more common in women than men. It can easily be confused with multiple sclerosis; this is why it is important to be able to recall the geographic regions where HTLV- I is endemic when evaluating a myelopathy. Acute T-cell leukemia is a difficult-to-treat leukemia that is specific to chronic HTLV- I infection. HTLV- I is thought to be transmitted in a similar fashion to HIV.
IV-161. The answer is C. (Chap. 189) Clindamycin plus primaquine is a therapeutic, not prophylactic, regimen for mild to moderate disease caused by Pneumocystis infection. Trimethoprim– sulfamethoxazole is usually given as a first-line agent but carries a significant side effect profile that includes hyperkalemia; renal insufficiency; elevation of serum creatinine; granulocytopenia; hemolysis in persons with G6PD insufficiency; and frequent allergic reactions, particularly in those with severe T-cell deficiency. Atovaquone is a common alternative that is given at the same dose for Pneumocystis prophylaxis as for therapy. Gastrointestinal symptoms are common with atovaquone. Aerosolized pentamidine can be given on a monthly basis with a risk of bronchospasm and pancreatitis. Patients who develop Pneumocystis pneumonia while receiving aerosolized pentamidine often have upper lobe–predominant disease. Dapsone is commonly used for Pneumocystis prophylaxis; however, the physician must be aware of the possibility of methemoglobinemia, G6PD-mediated hemolysis, rare hepatotoxicity, and rare hypersensitivity reaction when using this medicine.
IV-162. The answer is C. (Chap. 189) HIV/AIDS continues to have an extraordinary public health impact in the United States. As of January 1, 2010, an estimated 1,108,611 cases of AIDS had been diagnosed in the United States. Approximately 1.1 million individuals in the United States were living with HIV infection, approximately 20% of whom are unaware of their infection. Approximately two-thirds of those living with HIV/AIDS were nonwhite, and nearly half (48%) were men who have sex with men. The annual death rate from HIV/AIDS has fallen steadily in the past 15 years. This trend is attributable to several factors, including improved prophylaxis and treatment of opportunistic infections, the growing experience among health professions in caring for HIV-infected individuals,
improved access to health care, and a decrease in new infections because of saturational effects and prevention efforts. However, the most influential factor clearly has been the increased use of potent antiretroviral drugs, generally administered in a combination of three or four agents. After a decrease in the percentage of new HIV infections attributed to male-to-male sexual contact from 1985 to 1999, this percentage has increased. In 2009, this transmission category accounted for 48% of all AIDS diagnoses. The estimated percentage of AIDS diagnoses attributed to injection drug use increased from 20% to 31% from 1985 to 1994 and decreased since that time, accounting for 15% of diagnoses in 2009. The estimated percentage of AIDS diagnoses attributed to heterosexual contact increased from 3% in 1985 to 31% in 2009. HIV infection and AIDS have disproportionately affected minority populations in the United States. Among those diagnosed with HIV (regardless of AIDS status) in 2009, 52% percent were blacks, a group that constitutes only 12% of the U.S. population.
IV-163. The answer is C. (Chap. 189) The quoted risk for HIV transmission via a needle stick is 0.3%. This risk can be reduced to less than 0.1% if the at-risk health care worker is treated with antiretroviral therapy within 24 hours. The risk of transmission is likely highly variable according to a number of factors. Large-bore needle sticks where infected patient blood is visible are higher risk, as are deep tissue puncture to the health care provider. The patient’s degree of virologic control is generally inferred to be critical as well. Patients with viral loads below 1500/mL are considerably less likely to transmit via a needle stick than those with high viral loads. An extension of this point is that during acute and end-stage HIV infection, viral loads are extremely high, and contagion by needle stick is likely to be much higher. In addition, during end-stage disease, virulent viral forms predominate, which may increase the risk to an even greater extent. Each of these variables must be assessed rapidly after an accidental high-risk needle stick. Antiretroviral therapy (ART) is effective at preventing HIV transmission via needle stick if given before viral RNA incorporates into the host genome as proviral DNA. This is thought to occur within about 48 hours, but under the best scenario, ART should be given within 1 hour of a needle stick. Circumstances are often murky, with key information such as viral load, viral resistance history, and even HIV serostatus of the patient variably available; therefore, urgent consultation with an HIV or occupational health specialist is imperative after a needle stick. (Hepatitis B and C transmission must also be considered.)
IV-164. The answer is E. (Chap. 189) Abacavir use is associated with a potentially severe hypersensitivity reaction in about 5% of patients. There is likely a genetic component, with HLA-B*5701 being a significant risk factor for hypersensitivity syndrome. Symptoms, which usually occur within 2 weeks of therapy but can take more than 6 weeks to emerge, include fever, maculopapular rash, fatigue, malaise, gastrointestinal symptoms, and dyspnea. When a diagnosis is suspected, the drug should be stopped and never given again because rechallenge can be fatal. For this reason, both the diagnosis and patient education after the diagnosis is made must be performed thoroughly and carefully. It is important to note that two available combination pills contain abacavir (Epzicom, Trizivir), so patients must know to avoid these as well. Fanconi’s anemia is a rare disorder associated with tenofovir. Zidovudine causes anemia and sometimes granulocytopenia. Stavudine and other nucleoside reverse transcriptase inhibitors are associated with lipoatrophy of the face and legs.
IV-165. The answer is B. (Chap. 189) Cytomegalovirus (CMV) colitis should be considered in AIDS patients with CD4+ lymphocyte counts below 50/μL, fevers, and diarrhea. Diarrhea is often bloody but can be watery. Initial evaluation often involves stool studies to rule out other parasitic or bacterial
causes of diarrhea in AIDS patients. A standard panel includes some or all of the following depending on epidemiologic and historical data: Clostridium difficile stool antigen; stool culture; stool Mycobacterium avium intracellulare culture; stool ova and parasite examination; and special stains for Cryptosporidium, Isospora, Cyclospora, and Microsporidium spp. There is no stool or serum test that is useful for the evaluation of CMV colitis in an HIV-infected patient. A positive CMV immunoglobulin G result is merely a marker of past infection. If this test result is negative, then the pretest probability of developing active CMV decreases substantially. Serum CMV polymerase chain reaction (PCR) has gained utility in solid organ and bone marrow transplant patients for following treatment response for invasive CMV infection. However, in HIV-infected patients, CMV viremia correlates imprecisely with colitis. Furthermore, because CMV is a latent-lytic herpesvirus, a positive serum PCR does not imply disease unless drawn in the right clinical context, for which there is none in HIV infection. Colonic histology is sensitive and specific for the diagnosis of CMV colitis, with large-cell inclusion bodies being diagnostic.
IV-166. The answer is C. (Chap. 189) Immune reconstitution syndrome (IRIS) is commonly seen after the initiation of antiretroviral therapy (ART) in patients with AIDS and a concomitant opportunistic infection (OI). It is a syndrome in which either a previously recognized OI worsens after ART despite an initial period of improvement after standard therapy for that particular infection or in which an OI that was not previously recognized is unmasked after ART therapy. The latter scenario occurs presumably as immune cells become reactivated and recognize the presence of a pathogen that disseminated in the absence of adequate T-cell response with the patient remaining subclinical before ART. Many opportunistic pathogens are known to behave this way, but Cryptococcus spp., Mycobacterium tuberculosis, and Mycobacterium avium complex (MAI/MAC) are the most likely to be associated with IRIS. Risk factors for IRIS are a CD4+ lymphocyte count below 50/μL at ART initiation, initiation of ART within 2 months of treatment initiation for the OI, adequate virologic response to ART, and increase in CD4+ lymphocyte count as a result of ART. IRIS can be diagnostically challenging and is very diverse in terms of clinical presentation and severity. Depending on the organ system and pathogen involved, drug-resistant OI and new OI must be considered, sometimes necessitating invasive biopsies and cultures. In this case, the overlap of organ system with the original presentation, low likelihood of MAI drug resistance, and timing of the syndrome favor IRIS. Therapy is with nonsteroidal anti-inflammatory drugs and sometimes glucocorticoids. OI treatment is continued, and all efforts are made to continue ART as well except under the most dire of clinical circumstances.
IV-167. The answer is E. (Chap. 189) The biologic determinants of HIV transmission and acquisition are complex and have been difficult to study. However, several key factors are now known to increase the per-coital rate of HIV transmission, at least for heterosexual couples. In discordant couples, there is a dose-dependent relationship between serum viral load and HIV transmission. In fact, in carefully done studies, there was virtually no transmission between discordant couples when serum viral load was low (<400/mL). It is likely that this is attributable to a fairly tight correlation between serum and genital viral load. A corollary is that during acute HIV or AIDS, the viral load and therefore transmissibility are high. Strong clinical data from randomized trials indicate that circumcised men are less likely to acquire HIV because the interior surface of the foreskin is replete with cellular targets for HIV infection. Nonulcerative sexually transmitted infections cause mucosal breakdown that has been shown to allow for greater acquisition of HIV infection. Herpes simplex virus-2 (HSV-2) carriage (not
necessarily requiring active genital ulcer disease) leads to increases in HIV genital shedding as well as HIV-1 target cell migration to the genital mucosa, making both transmission and acquisition of HIV higher in HSV-2–positive persons.
IV-168. The answer is B. (Chap. 189) Centers for Disease Control and Prevention guidelines now state that all adults should receive HIV testing, with the availability of a patient opt-out mechanism rather than informed consent. The basis for this is that about 25% of the 1 million Americans infected with HIV are unaware of their status, there is good available treatment for HIV that serves to extend the lifespan and decrease HIV transmission, and HIV testing is shown to correlate with a decrease in risk-taking behaviors. Cost-benefit analysis has suggested this approach has advantages to current approaches focusing on screening high-risk populations. Pretest counseling is desirable but not always built into the testing process, so physicians should provide some degree of preparation for a positive test result. If the diagnosis is made, support systems should be activated that may include trained nurses, social workers, or community support centers.
IV-169. The answer is A. (Chap. 189) This patient most likely has HIV encephalopathy of moderate severity. Other neurologic conditions associated with HIV may be considered with a broad initial workup, but her reasonably high CD4+ count, lack of focal deficits, and lack of mass lesions on high-resolution brain imaging makes toxoplasmosis, central nervous system (CNS) tuberculoma, progressive multifocal leukoencephalopathy (PML), and CNS lymphoma all less unlikely. Immediate highly active antiretroviral therapy is the treatment of choice for HIV encephalopathy, and she warrants this despite her CD4+ lymphocyte count, placing her in a gray zone according to current guidelines in regards to starting therapy. A lumbar puncture for the Venereal Disease Research Laboratory test is unnecessary because a serum rapid plasma reagin test is a very good screening test for any type of syphilis; JC virus detected in the cerebrospinal fluid would suggest PML, but her pretest probability for this is low because it usually affects patients with low CD4+ T-cell counts. Serum cryptococcal antigen has excellent performance characteristics, but there is little reason to suspect cryptococcal meningitis in the absence of headache or elevated intracerebral pressure.
IV-170. The answer is D. (Chap. 189) Indinavir is the only agent to cause nephrolithiasis. Nucleoside reverse transcriptase inhibitors, particularly stavudine and didanosine (d4T and ddI), are associated with mitochondrial toxicity and pancreatitis. Nevirapine can cause hepatic necrosis in women, particularly with CD4+ lymphocyte counts above 350/μL. Efavirenz, a very commonly used agent, causes dream disturbances that usually, but not always, subside after the first month of therapy. Both indinavir and atazanavir cause a benign indirect hyperbilirubinemia reminiscent of Gilbert’s syndrome.
IV-171. The answer is D. (Chap. 189) Isospora and Cryptosporidium spp. cause very similar clinical disease in AIDS patients that ranges from intermittent, self-resolved watery diarrhea with abdominal cramping and sometimes nausea to a potentially fatal cholera-like presentation in the most immunocompromised hosts. Cryptosporidium spp. may cause biliary disease and can lead to cholangitis. Isospora spp. is limited to the gut lumen. Cryptosporidium spp. is not always an opportunistic infection and has led to widespread community outbreaks. Isospora spp. is not seen in immunocompetent hosts. Finally, treatment for Isospora infection is usually successful. In fact, this infection is rarely seen in the developed world because trimethoprim–sulfamethoxazole, which is commonly used for Pneumocystis prophylaxis, tends to eradicate Isospora spp. Cryptosporidiosis, on the other hand, is very difficult to cure, and interventions are controversial. Some clinicians favor
nitazoxanide, but cure rates are mediocre, and immune reconstitution with antiretroviral therapy is ultimately critical to cure the gastrointestinal disease.
IV-172. The answer is D. (Chap. 189) Acute HIV should be suspected in any at-risk person who presents with a mono-like illness; it is diagnosed by positive plasma RNA polymerase chain reaction (PCR). Patients typically have not developed sufficient antibodies to the virus yet to develop a positive enzyme immunoassay result, and the diagnosis of HIV is usually missed if this test is sent within the first 2 months of HIV acquisition. It is tempting for clinicians to send an ultrasensitive PCR, but this only decreases specificity (false-positive tests with detection of very low levels of HIV are possible because of cross-contamination in the laboratory) with no other benefit. There is typically a massive amount of HIV virus in the plasma during acute infection, and the ultrasensitive assay is never required for detection at this stage of disease. Ultrasensitive assays are helpful in the context of therapy to ensure that there is not persistence of low-level viremia. CD4+ lymphocyte count decreases during many acute infections, including HIV, and is therefore not diagnostically appropriate. CD4+ lymphocyte counts are useful to risk stratify for opportunistic infection in stable patients with known HIV infection. Resistance tests are sent only when the diagnosis is confirmed.
IV-173. The answer is B. (Chap. 189) Oral hairy leukoplakia is caused by a severe overgrowth of Epstein-Barr virus infection in T-cell–deficient patients. It is not premalignant and is often unrecognized by the patient but is sometimes a cosmetic, symptomatic, and therapeutic nuisance. The white, thickened folds on the side of the tongue can be pruritic or painful and sometimes resolve with acyclovir derivatives or topical podophyllin resin. Ultimate resolution occurs after immune reconstitution with antiretroviral therapy. Oral candidiasis or thrush is a very common, relatively easy-to-treat condition in HIV patients and takes on an appearance of white plaques on the tongue, palate, and buccal mucosa that bleed with blunt removal. Herpes simplex virus (HSV) recurrences or aphthous ulcers present as painful ulcerating lesions. The latter should be considered when oral ulcers persist, do not respond to acyclovir, and do not culture HSV. Kaposi’s sarcoma is uncommon in the oropharynx and takes on a violet hue, suggesting its highly vascularized content.
IV-174. The answer is E. (Chap. 189) Current recommendations are to initiate antiretroviral therapy in patients with the acute HIV syndrome, all pregnant women, patients with an AIDS-defining illness, patients with HIV-associated nephropathy, and patients with asymptomatic disease with CD4+ T-cell counts below 500/μL. Clinical trials are under way to determine the value of even earlier intervention, and some experts would place everyone with HIV infection on antiretroviral therapy. In addition, one may wish to administer a 6-week course of therapy to uninfected individuals immediately after a high-risk exposure to HIV. For patients diagnosed with an opportunistic infection and HIV infection at the same time, one may consider a 2- to 4-week delay in the initiation of antiretroviral therapy during which time treatment is focused on the opportunistic infection. Although not proven, it is postulated that this delay may decrease the severity of any subsequent immune reconstitution inflammatory syndrome by lowering the antigenic burden of the opportunistic infection.