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Health Care-Associated lnfections f EY P0I1{TS (corilinued) plus clinical findings, including new-onset fever (temperature >38 oC [too.+ 'F]), leukocytosis or leukopenia, purulent spu- o Vancomycin and daptomycin are the preferred antibiot- tum, and decline in oxygenation, suggest pneumonia. ics for methicillin-resistant Staphylococcus oureus bac- Noninvasive sampling (endotracheal aspiration) with semi- teremia, although patients with concomitant S. oureus quantitative sputum cultures (hear,ry', moderate, light, and no pneumonia should not receive daptomycin because it is growth) are suggested for diagnosing VAP. Clinical findings inactivated by surfactant. without radiographic support suggest tracheobronchitis, which does not require antibiotic treatment. Hospital-Acquired Pneumonia and Treatment Ve nti lator-Associated Pneu mo n ia Respiratory sample culture results should guide therapy for Hospital-acquired pneumonia (HAP) is pneumonia developing suspected HAP; a specimen from the lower respiratory tract more than 48 hours after hospitalization. Ventilator-associated should be obtained before starting antimicrobial therapy. pneumonia (VAP) is pneumonia developing 48 hours after However, inability to obtain a specimen should not delay endotracheal intubation; it occurs in 107, of patients undergoing therapy initiation for VAB and empiric antimicrobial therapy ventilation. Half of patients with HAP develop serious compli- should be instituted for patients with VAP pending results of cations, including respiratory failure, pleural effusion, septic noninvasive sampling with semiquantitative cultures and shock, empyema, and kidney injury. Mechanical ventilation based on local VAP antibiograms, if available. increases the risk of pneumonia 6-fold to 2l-fold. HAP and VAP Empiric VAP regimens should include coverage for S. risk factors include age older thanTO years, recent abdominal or altreus, P. aeruginoso, and other gram-negative bacilli. An thoracic surgery immunosuppression, and underlying chronic agent active against MRSA (vancomycin, linezolid) should be lung disease. Modifiable risk factors are listed in Table 59. included for patients with MRSA risk factors or those in a unit HAP and VAP are most commonly caused by bacteria, but with MRSA prevalence greater than 10'2, to 20% or unknown. viral and fungal pathogens should be considered in immuno- Two antipseudomonal agents of different classes are recom- compromised patients. The main risk factor for MRSA, antibiotic- mended for empiric regimens only for patients with risk fac- resistant Pseudomonos, or other antibiotic-resistant pathogens is tors for resistance, with structural lung disease (bronchiectasis, intravenous antibiotic use within the past 90 days. Additional risk cystic fibrosis), or in a unit with greater than 10% resistance to factors for multidrug-resistant pathogens associatedwith VAP are an agent being considered for monotherapy. Similar regimens septic shock at the time of VAB acute respiratory distress qm- are recommended for patients with HAP who are treated drome preceding VAB S or more days of hospitalization before empirically. Antimicrobial coverage for oral anaerobes may be VAB and acute kidney replacement therapy before VAP considered in patients with witnessed aspiration events or recent surgery but is not routinely recommended unless lung Diagnosis abscess or empyema is suspected. Cephalosporins should be Diagnosis relies on a combination of clinical, radiographic, avoided as monotherapy in settings where extended-spectrum and microbiologic findings. A new lung infiltrate on imaging B-lactamase (ESBL)-producing gram-negative organisms (such as K. pneumoniae\ are prevalent; consider a carba- TABLE 59. Mitigation of Risk Factors for Ventilator- penem instead. VAP caused by gram-negative organisms Associated Pneumonia sensitive only to aminoglycosides or colistin may be treated Risk Factor lntervention with a combination of systemic and aerosolized antibiotics. Mechanical Consider noninvasive, positive-pressure Microbiologic results should be reviewed at 48 to 72 hours, ventilation ventilation and all patients should be re-evaluated for clinical improve- Sedation Minimize ment. Antimicrobial therapy should be de-escalated (to nar- lntermittent infusions or daily interruption row-spectrum or oral therapy) based on microbiologic results and daily assessment of readiness for and clinical stabilization or discontinued if the diagnosis of extubation pneumonia is in doubt. Patients who do not improve within Supine position Risk highest for patients receiving enteral 72 hours of appropriate therapy should undergo investigation for nutrition infectious complications, an alternate diagnosis, or another site Elevate head of bed 30"-45" of infection. HAP and VAP should be treated for 7 days or less. Oropharyngeal Daily oral care; oral care with colonization chlorhexidine may be beneficial in some Prevention patients Commonly used ventilator bundles include subglottic suction- Physical Facilitate early mobility (speeds ing, peptic ulcer disease and deep venous thrombosis prophy- conditioning extubation) laxis, and avoiding gastric overdistention. Use of ventilator Reintubation Consider noninvasive, positive-pressure ventilation bundies has been shown to decrease VAP rates by Zl%. Additional interventions are listed in Table 59.

f EY P0I1{TS (corilinued) plus clinical findings, including new-onset fever (temperature >38 oC [too.+ 'F]), leukocytosis or leukopenia, purulent spu- o Vancomycin and daptomycin are the preferred antibiot- tum, and decline in oxygenation, suggest pneumonia. ics for methicillin-resistant Staphylococcus oureus bac- Noninvasive sampling (endotracheal aspiration) with semi- teremia, although patients with concomitant S. oureus quantitative sputum cultures (hear,ry', moderate, light, and no pneumonia should not receive daptomycin because it is growth) are suggested for diagnosing VAP. Clinical findings inactivated by surfactant. without radiographic support suggest tracheobronchitis, which does not require antibiotic treatment. Hospital-Acquired Pneumonia and Treatment Ve nti lator-Associated Pneu mo n ia Respiratory sample culture results should guide therapy for Hospital-acquired pneumonia (HAP) is pneumonia developing suspected HAP; a specimen from the lower respiratory tract more than 48 hours after hospitalization. Ventilator-associated should be obtained before starting antimicrobial therapy. pneumonia (VAP) is pneumonia developing 48 hours after However, inability to obtain a specimen should not delay endotracheal intubation; it occurs in 107, of patients undergoing therapy initiation for VAB and empiric antimicrobial therapy ventilation. Half of patients with HAP develop serious compli- should be instituted for patients with VAP pending results of cations, including respiratory failure, pleural effusion, septic noninvasive sampling with semiquantitative cultures and shock, empyema, and kidney injury. Mechanical ventilation based on local VAP antibiograms, if available. increases the risk of pneumonia 6-fold to 2l-fold. HAP and VAP Empiric VAP regimens should include coverage for S. risk factors include age older thanTO years, recent abdominal or altreus, P. aeruginoso, and other gram-negative bacilli. An thoracic surgery immunosuppression, and underlying chronic agent active against MRSA (vancomycin, linezolid) should be lung disease. Modifiable risk factors are listed in Table 59. included for patients with MRSA risk factors or those in a unit HAP and VAP are most commonly caused by bacteria, but with MRSA prevalence greater than 10'2, to 20% or unknown. viral and fungal pathogens should be considered in immuno- Two antipseudomonal agents of different classes are recom- compromised patients. The main risk factor for MRSA, antibiotic- mended for empiric regimens only for patients with risk fac- resistant Pseudomonos, or other antibiotic-resistant pathogens is tors for resistance, with structural lung disease (bronchiectasis, intravenous antibiotic use within the past 90 days. Additional risk cystic fibrosis), or in a unit with greater than 10% resistance to factors for multidrug-resistant pathogens associatedwith VAP are an agent being considered for monotherapy. Similar regimens septic shock at the time of VAB acute respiratory distress qm- are recommended for patients with HAP who are treated drome preceding VAB S or more days of hospitalization before empirically. Antimicrobial coverage for oral anaerobes may be VAB and acute kidney replacement therapy before VAP considered in patients with witnessed aspiration events or recent surgery but is not routinely recommended unless lung Diagnosis abscess or empyema is suspected. Cephalosporins should be Diagnosis relies on a combination of clinical, radiographic, avoided as monotherapy in settings where extended-spectrum and microbiologic findings. A new lung infiltrate on imaging B-lactamase (ESBL)-producing gram-negative organisms (such as K. pneumoniae\ are prevalent; consider a carba- TABLE 59. Mitigation of Risk Factors for Ventilator- penem instead. VAP caused by gram-negative organisms Associated Pneumonia sensitive only to aminoglycosides or colistin may be treated Risk Factor lntervention with a combination of systemic and aerosolized antibiotics. Mechanical Consider noninvasive, positive-pressure Microbiologic results should be reviewed at 48 to 72 hours, ventilation ventilation and all patients should be re-evaluated for clinical improve- Sedation Minimize ment. Antimicrobial therapy should be de-escalated (to nar- lntermittent infusions or daily interruption row-spectrum or oral therapy) based on microbiologic results and daily assessment of readiness for and clinical stabilization or discontinued if the diagnosis of extubation pneumonia is in doubt. Patients who do not improve within Supine position Risk highest for patients receiving enteral 72 hours of appropriate therapy should undergo investigation for nutrition infectious complications, an alternate diagnosis, or another site Elevate head of bed 30"-45" of infection. HAP and VAP should be treated for 7 days or less. Oropharyngeal Daily oral care; oral care with colonization chlorhexidine may be beneficial in some Prevention patients Commonly used ventilator bundles include subglottic suction- Physical Facilitate early mobility (speeds ing, peptic ulcer disease and deep venous thrombosis prophy- conditioning extubation) laxis, and avoiding gastric overdistention. Use of ventilator Reintubation Consider noninvasive, positive-pressure ventilation bundies has been shown to decrease VAP rates by Zl%. Additional interventions are listed in Table 59. 86

H rvlAt Ds r(EY POrr{TS l( EY P0 r ltTS . The diagnosis of hospital-acquired and ventilator-asso- . Multidrug-resistant organisms are most prevalent in ciated pneumonia are suggested by a new lung infiltrate health care settings (highest incidence in long-term on imaging plus clinical findings, including new-onset acute care hospitals)but are also observed in the fever, leukocytosis or leukopenia, purulent sputum, and communit5r. decline in oxygenation. o Limiting emergence and transmission of multidrug- HVC . Empiric ventilator-associated pneumonia regimens resistant organisms in health care settings requires full should include coverage for Staphylococcus aureus, adherence to hand hygiene protocols, contact precau- Pseudomonas aer ugino se, and other gram- negative tions, cleaning and disinfecting of the environment and bacilli; an agent active against methicillin-resistant equipment, and judicious use of antimicrobial agents. S. aureus (MRSA) should be included for patients with MRSA risk factors or where MRSA prevalence exceeds 10'/o (or is unknown); similar regimens are recom- mended for empiric hospital-acquired pneumonia HIV/AIDS treatment. HIV infection remains a significant global health concern . In patients receiving mechanical ventilation, the head despite being a treatable disease. Many persons living with of the bed should be elevated 30o to 45o; & supine posi- HIV infection are not aware of their status because they have tion, particularly in patients receiving enteral nutrition, never been tested; others have been diagnosed but are not increases the risk for developing ventilator-associated receiving care. This chapterwill focus on HIV-1. Infection with pneumonia. HIV-2 primarily occurs in parts of Africa and remains rare in the United States; HIV-2 generally is a less progressive disease with less immunocompromise and lower risk of opporlunistic Hospital-Acq uired I nfections infections. Testing for HIV infection detects HIV-1 and HIV-2 Caused by Multidrug-Resistant antibodies (see Screening and Diagnosis).

r(EY POrr{TS l( EY P0 r ltTS . The diagnosis of hospital-acquired and ventilator-asso- . Multidrug-resistant organisms are most prevalent in ciated pneumonia are suggested by a new lung infiltrate health care settings (highest incidence in long-term on imaging plus clinical findings, including new-onset acute care hospitals)but are also observed in the fever, leukocytosis or leukopenia, purulent sputum, and communit5r. decline in oxygenation. o Limiting emergence and transmission of multidrug- HVC . Empiric ventilator-associated pneumonia regimens resistant organisms in health care settings requires full should include coverage for Staphylococcus aureus, adherence to hand hygiene protocols, contact precau- Pseudomonas aer ugino se, and other gram- negative tions, cleaning and disinfecting of the environment and bacilli; an agent active against methicillin-resistant equipment, and judicious use of antimicrobial agents. S. aureus (MRSA) should be included for patients with MRSA risk factors or where MRSA prevalence exceeds 10'/o (or is unknown); similar regimens are recom- mended for empiric hospital-acquired pneumonia HIV/AIDS treatment. HIV infection remains a significant global health concern . In patients receiving mechanical ventilation, the head despite being a treatable disease. Many persons living with of the bed should be elevated 30o to 45o; & supine posi- HIV infection are not aware of their status because they have tion, particularly in patients receiving enteral nutrition, never been tested; others have been diagnosed but are not increases the risk for developing ventilator-associated receiving care. This chapterwill focus on HIV-1. Infection with pneumonia. HIV-2 primarily occurs in parts of Africa and remains rare in the United States; HIV-2 generally is a less progressive disease with less immunocompromise and lower risk of opporlunistic Hospital-Acq uired I nfections infections. Testing for HIV infection detects HIV-1 and HIV-2 Caused by Multidrug-Resistant antibodies (see Screening and Diagnosis). Organisms Antimicrobial resistance has been noted in nearly all bacterial Prevention pathogens. Multidrug-resistant organisms (l,lpROs) are most HIV transmission occurs through sexual contact or exposure prevalent in health care settings (highest incidence in long- to other body fluids (table 6O). Reducing transmission can be term acute care hospitals) but are also observed in the com- accomplished by using barrier methods, such as condoms munity. Nearly half of S. oureus HCAIs in the United States are during sexual contact, and through clean syringe services pro methicillin resistant, about 30o1, of enterococci are vancomycin grams (needle exchange programs) for persons who inject resistant, 20.7"L of Enterobacteriaceae produce ESBL and are drugs. Universal blood donor testing has all but eliminated resistant to all B-lactam antibiotics, 3.3o1, of Enterobacteriaceae infection through blood transfusion in the United States, with are resistant to carbapenems, andl4.2"/. of P aeruginoso and current risk estimated to be one in 2 million. 43.1"1, of Acinetobacter species are multidrug resistant (some Antiretroviral therapy (ART) has extraordinary potential Acinetobacter are resistant to nearly all antibiotics). to reduce new infections in addition to benefiting the treated Candida auris is an emerging drug-resistant pathogen person. Successful treatment is associated with significant shed from patients' skin into the environment, where it can reductions in HIV transmission. Although reducing viral load survive for weeks and be transmitted to other patients. It to an undetectable ievel in blood does not prove absence of causes severe invasive infections, particularly in immuno- virus in semen or vaginal fluid, the rate of transmission from a compromised patients. See Fungal Infections for additional information. TABLE 60. Risk of HIV-1 Transmission per Single Exposure MDRO infections are difficult to treat, with mortality Exposure Risk (%) rates up to four times higher than infections caused by Occu pationa l-need lestick 0.23 antibiotic-sensitive strains. Limiting transmission of MDROs Occupational-mucous membrane 0.09 in health care settings requires full adherence to hand hygiene Needle-sharing injection drug use 0.63 protocols, contact precautions, and cleaning and disinfecting Receptive anal intercourse 1.4 of the environment and patient care equipment. More than half of hospitalized patients receive antibiotics, a major risk for Receptive vagi na I i ntercou rse 0.08 acquiring an antibiotic-resistant organism and C. dfficile I nsertive a nal intercou rse 0.11 infection. Judicious use of antimicrobial agents is increasingly I nsertive va gi na I i ntercou rse 0.04 important to combat the rise of MDROs and emergence of 0.01 Oralsex untreatable infections.

Organisms Antimicrobial resistance has been noted in nearly all bacterial Prevention pathogens. Multidrug-resistant organisms (l,lpROs) are most HIV transmission occurs through sexual contact or exposure prevalent in health care settings (highest incidence in long- to other body fluids (table 6O). Reducing transmission can be term acute care hospitals) but are also observed in the com- accomplished by using barrier methods, such as condoms munity. Nearly half of S. oureus HCAIs in the United States are during sexual contact, and through clean syringe services pro methicillin resistant, about 30o1, of enterococci are vancomycin grams (needle exchange programs) for persons who inject resistant, 20.7"L of Enterobacteriaceae produce ESBL and are drugs. Universal blood donor testing has all but eliminated resistant to all B-lactam antibiotics, 3.3o1, of Enterobacteriaceae infection through blood transfusion in the United States, with are resistant to carbapenems, andl4.2"/. of P aeruginoso and current risk estimated to be one in 2 million. 43.1"1, of Acinetobacter species are multidrug resistant (some Antiretroviral therapy (ART) has extraordinary potential Acinetobacter are resistant to nearly all antibiotics). to reduce new infections in addition to benefiting the treated Candida auris is an emerging drug-resistant pathogen person. Successful treatment is associated with significant shed from patients' skin into the environment, where it can reductions in HIV transmission. Although reducing viral load survive for weeks and be transmitted to other patients. It to an undetectable ievel in blood does not prove absence of causes severe invasive infections, particularly in immuno- virus in semen or vaginal fluid, the rate of transmission from a compromised patients. See Fungal Infections for additional information. TABLE 60. Risk of HIV-1 Transmission per Single Exposure MDRO infections are difficult to treat, with mortality Exposure Risk (%) rates up to four times higher than infections caused by Occu pationa l-need lestick 0.23 antibiotic-sensitive strains. Limiting transmission of MDROs Occupational-mucous membrane 0.09 in health care settings requires full adherence to hand hygiene Needle-sharing injection drug use 0.63 protocols, contact precautions, and cleaning and disinfecting Receptive anal intercourse 1.4 of the environment and patient care equipment. More than half of hospitalized patients receive antibiotics, a major risk for Receptive vagi na I i ntercou rse 0.08 acquiring an antibiotic-resistant organism and C. dfficile I nsertive a nal intercou rse 0.11 infection. Judicious use of antimicrobial agents is increasingly I nsertive va gi na I i ntercou rse 0.04 important to combat the rise of MDROs and emergence of 0.01 Oralsex untreatable infections. 87

H rv/ArDs sexual partner with undetectable blood viral load has been (see Management of Pregnant Patients for information on demonstrated to be close to zero, at a level the CDC called dolutegravir in pregnancy). The exposed person should "effectively no risk" in a September 2Ol7 statement; hence the undergo HIV testing at baseline and at 4to 6 weeks, 3 months, slogan "Undetectable = Untransmissible" ("U=U"). Also and 6 months after exposure. Figure 35 shows an algorithm for termed "treatment as prevention" (TasP), maintaining an HIV evaluation of possible HIV exposure. RNA level less than 200 copies/ml (documented for >6 The U.S. Preventive Services Task Force (USPSTF) and months) with ART prevents HIV transmission to sexual part- CDC recommend pre-exposure prophylaxis (PrEP) with ART ners. In what is known as the "treatment cascade," medical to reduce the risk of infection for persons at high risk of HIV care necessary to achieve successful viral suppression consists acquisition, including men who have sex with men, persons at of testing and diagnosing infected persons, linking them to risk through heterosexual contact, and persons who inject health care for counseling and treatment, keeping them in a drugs (Table 61). A two-drug combination of TDF and emtri- treatment program, and ensuring antiretroviral and other citabine, taken once daily, is FDA approved for HIV PrEP; treatment adherence. Each step along this continuum of care with proven adherence, it has been shown to be more than is a potential obstacle to successful HIV management on a 90'lu effective in reducing infection in those at high risk. personal and public health level. Even high-income countries Additionally, the FDA recently approved once-daily tenofovir have poor rates of retention in care and adherence to medica alafenamide (TAF) and emtricitabine for HIV PrEP, excluding tion. The CDC estimates that the undiagnosed and not-in care in persons who have receptive vaginal intercourse. Patients groups with HIV infection were responsible for B0ol, of HIV should also be counseled on the need to continue barrier pre- transmissions in the United States in 2016. cautions, on medication toxicity, and on continued risk for Postexposure prophylaxis has been used successfully for other sexually transmitted infections (STIs). Testing should be many years to prevent infection after occupational and nonoc performed for HIV hepatitis B virus (HBV), kidney function, cupational HIV exposure. Prophylaxis should be started as and pregnancy before PrEP initiation; monitoring for HIV soon as possible after exposure; it is not recommended if more other STIs, and pregnancy every 3 months and performing than72 hours have passed. A three-drug regimen is given for 4 kidney function assessment every 6 months are also recom- weeks; the preferred regimen is tenofovir disoproxil fumarate mended during PrEP therapy. Persons taking PrEP who (TDF) and emtricitabine plus either raltegravir or dolutegravir test positive for HIV should have a third drug (either

sexual partner with undetectable blood viral load has been (see Management of Pregnant Patients for information on demonstrated to be close to zero, at a level the CDC called dolutegravir in pregnancy). The exposed person should "effectively no risk" in a September 2Ol7 statement; hence the undergo HIV testing at baseline and at 4to 6 weeks, 3 months, slogan "Undetectable = Untransmissible" ("U=U"). Also and 6 months after exposure. Figure 35 shows an algorithm for termed "treatment as prevention" (TasP), maintaining an HIV evaluation of possible HIV exposure. RNA level less than 200 copies/ml (documented for >6 The U.S. Preventive Services Task Force (USPSTF) and months) with ART prevents HIV transmission to sexual part- CDC recommend pre-exposure prophylaxis (PrEP) with ART ners. In what is known as the "treatment cascade," medical to reduce the risk of infection for persons at high risk of HIV care necessary to achieve successful viral suppression consists acquisition, including men who have sex with men, persons at of testing and diagnosing infected persons, linking them to risk through heterosexual contact, and persons who inject health care for counseling and treatment, keeping them in a drugs (Table 61). A two-drug combination of TDF and emtri- treatment program, and ensuring antiretroviral and other citabine, taken once daily, is FDA approved for HIV PrEP; treatment adherence. Each step along this continuum of care with proven adherence, it has been shown to be more than is a potential obstacle to successful HIV management on a 90'lu effective in reducing infection in those at high risk. personal and public health level. Even high-income countries Additionally, the FDA recently approved once-daily tenofovir have poor rates of retention in care and adherence to medica alafenamide (TAF) and emtricitabine for HIV PrEP, excluding tion. The CDC estimates that the undiagnosed and not-in care in persons who have receptive vaginal intercourse. Patients groups with HIV infection were responsible for B0ol, of HIV should also be counseled on the need to continue barrier pre- transmissions in the United States in 2016. cautions, on medication toxicity, and on continued risk for Postexposure prophylaxis has been used successfully for other sexually transmitted infections (STIs). Testing should be many years to prevent infection after occupational and nonoc performed for HIV hepatitis B virus (HBV), kidney function, cupational HIV exposure. Prophylaxis should be started as and pregnancy before PrEP initiation; monitoring for HIV soon as possible after exposure; it is not recommended if more other STIs, and pregnancy every 3 months and performing than72 hours have passed. A three-drug regimen is given for 4 kidney function assessment every 6 months are also recom- weeks; the preferred regimen is tenofovir disoproxil fumarate mended during PrEP therapy. Persons taking PrEP who (TDF) and emtricitabine plus either raltegravir or dolutegravir test positive for HIV should have a third drug (either Substantial risk Negligible risk for HIV Acquisition for HlVAcquisition

sexual partner with undetectable blood viral load has been (see Management of Pregnant Patients for information on demonstrated to be close to zero, at a level the CDC called dolutegravir in pregnancy). The exposed person should "effectively no risk" in a September 2Ol7 statement; hence the undergo HIV testing at baseline and at 4to 6 weeks, 3 months, slogan "Undetectable = Untransmissible" ("U=U"). Also and 6 months after exposure. Figure 35 shows an algorithm for termed "treatment as prevention" (TasP), maintaining an HIV evaluation of possible HIV exposure. RNA level less than 200 copies/ml (documented for >6 The U.S. Preventive Services Task Force (USPSTF) and months) with ART prevents HIV transmission to sexual part- CDC recommend pre-exposure prophylaxis (PrEP) with ART ners. In what is known as the "treatment cascade," medical to reduce the risk of infection for persons at high risk of HIV care necessary to achieve successful viral suppression consists acquisition, including men who have sex with men, persons at of testing and diagnosing infected persons, linking them to risk through heterosexual contact, and persons who inject health care for counseling and treatment, keeping them in a drugs (Table 61). A two-drug combination of TDF and emtri- treatment program, and ensuring antiretroviral and other citabine, taken once daily, is FDA approved for HIV PrEP; treatment adherence. Each step along this continuum of care with proven adherence, it has been shown to be more than is a potential obstacle to successful HIV management on a 90'lu effective in reducing infection in those at high risk. personal and public health level. Even high-income countries Additionally, the FDA recently approved once-daily tenofovir have poor rates of retention in care and adherence to medica alafenamide (TAF) and emtricitabine for HIV PrEP, excluding tion. The CDC estimates that the undiagnosed and not-in care in persons who have receptive vaginal intercourse. Patients groups with HIV infection were responsible for B0ol, of HIV should also be counseled on the need to continue barrier pre- transmissions in the United States in 2016. cautions, on medication toxicity, and on continued risk for Postexposure prophylaxis has been used successfully for other sexually transmitted infections (STIs). Testing should be many years to prevent infection after occupational and nonoc performed for HIV hepatitis B virus (HBV), kidney function, cupational HIV exposure. Prophylaxis should be started as and pregnancy before PrEP initiation; monitoring for HIV soon as possible after exposure; it is not recommended if more other STIs, and pregnancy every 3 months and performing than72 hours have passed. A three-drug regimen is given for 4 kidney function assessment every 6 months are also recom- weeks; the preferred regimen is tenofovir disoproxil fumarate mended during PrEP therapy. Persons taking PrEP who (TDF) and emtricitabine plus either raltegravir or dolutegravir test positive for HIV should have a third drug (either Substantial risk Negligible risk for HIV Acquisition for HlVAcquisition <72hours >73 hours since exposure since exposure

sexual partner with undetectable blood viral load has been (see Management of Pregnant Patients for information on demonstrated to be close to zero, at a level the CDC called dolutegravir in pregnancy). The exposed person should "effectively no risk" in a September 2Ol7 statement; hence the undergo HIV testing at baseline and at 4to 6 weeks, 3 months, slogan "Undetectable = Untransmissible" ("U=U"). Also and 6 months after exposure. Figure 35 shows an algorithm for termed "treatment as prevention" (TasP), maintaining an HIV evaluation of possible HIV exposure. RNA level less than 200 copies/ml (documented for >6 The U.S. Preventive Services Task Force (USPSTF) and months) with ART prevents HIV transmission to sexual part- CDC recommend pre-exposure prophylaxis (PrEP) with ART ners. In what is known as the "treatment cascade," medical to reduce the risk of infection for persons at high risk of HIV care necessary to achieve successful viral suppression consists acquisition, including men who have sex with men, persons at of testing and diagnosing infected persons, linking them to risk through heterosexual contact, and persons who inject health care for counseling and treatment, keeping them in a drugs (Table 61). A two-drug combination of TDF and emtri- treatment program, and ensuring antiretroviral and other citabine, taken once daily, is FDA approved for HIV PrEP; treatment adherence. Each step along this continuum of care with proven adherence, it has been shown to be more than is a potential obstacle to successful HIV management on a 90'lu effective in reducing infection in those at high risk. personal and public health level. Even high-income countries Additionally, the FDA recently approved once-daily tenofovir have poor rates of retention in care and adherence to medica alafenamide (TAF) and emtricitabine for HIV PrEP, excluding tion. The CDC estimates that the undiagnosed and not-in care in persons who have receptive vaginal intercourse. Patients groups with HIV infection were responsible for B0ol, of HIV should also be counseled on the need to continue barrier pre- transmissions in the United States in 2016. cautions, on medication toxicity, and on continued risk for Postexposure prophylaxis has been used successfully for other sexually transmitted infections (STIs). Testing should be many years to prevent infection after occupational and nonoc performed for HIV hepatitis B virus (HBV), kidney function, cupational HIV exposure. Prophylaxis should be started as and pregnancy before PrEP initiation; monitoring for HIV soon as possible after exposure; it is not recommended if more other STIs, and pregnancy every 3 months and performing than72 hours have passed. A three-drug regimen is given for 4 kidney function assessment every 6 months are also recom- weeks; the preferred regimen is tenofovir disoproxil fumarate mended during PrEP therapy. Persons taking PrEP who (TDF) and emtricitabine plus either raltegravir or dolutegravir test positive for HIV should have a third drug (either Substantial risk Negligible risk for HIV Acquisition for HlVAcquisition <72hours >73 hours since exposure since exposure Source patient Source patient known to be of unknown HIV-positive HIV status

<72hours >73 hours since exposure since exposure Source patient Source patient known to be of unknown HIV-positive HIV status nPEP Case-by-case nPEP not recommended determination recommended Substantial Risk for HIV Acquisition Negligible Risk for HIV Acquisition

Source patient Source patient known to be of unknown HIV-positive HIV status nPEP Case-by-case nPEP not recommended determination recommended Substantial Risk for HIV Acquisition Negligible Risk for HIV Acquisition Exposure of Exposure of vagina, rectum, eye, mouth, or other vagina, rectum, eye, mouth, or other mucous membrane, nonintact skin, or mucous membrane, intact or nonintact percutaneous contact skin, or percutaneous contact FIGURE 35. Algorithm for evaluation and treatment of possible with with HIV exposure. nPEP = nonoccupational blood, semen, vaginal secretions, rectal urine, nasal secretions, saliva, sweat, or postexposu re prophylaxis. secretions, breast milk, or any body fluid tears if not visibly contaminated with blood that is visibly contaminated with blood Centers for Disease Control and Prevention. Updated guidelines for antiretroviral postexposure prophylaxis Regard/ess after sexual, injection drug use, or other nonoccupa- When of the known or suspected HIV status tional exposure to HIV-United States,2016. Available the source is known to be HlV-positive of the source at https ://stacks.cdc. gov/viewkdc/38856. Accessed January 29, 201 B.

Exposure of Exposure of vagina, rectum, eye, mouth, or other vagina, rectum, eye, mouth, or other mucous membrane, nonintact skin, or mucous membrane, intact or nonintact percutaneous contact skin, or percutaneous contact FIGURE 35. Algorithm for evaluation and treatment of possible with with HIV exposure. nPEP = nonoccupational blood, semen, vaginal secretions, rectal urine, nasal secretions, saliva, sweat, or postexposu re prophylaxis. secretions, breast milk, or any body fluid tears if not visibly contaminated with blood that is visibly contaminated with blood Centers for Disease Control and Prevention. Updated guidelines for antiretroviral postexposure prophylaxis Regard/ess after sexual, injection drug use, or other nonoccupa- When of the known or suspected HIV status tional exposure to HIV-United States,2016. Available the source is known to be HlV-positive of the source at https ://stacks.cdc. gov/viewkdc/38856. Accessed January 29, 201 B. 88

H rvlAt Ds TABLE 61. Persons at High Risk of HlVAcquisition Who TABLE 62. Signs and Symptoms of Acute HIV lnfection Should be Considered for PrEP" (Acute Retroviral Syndrome) Men Who Have Heterosexual Persons Who Use Sign/Symptom Frequency (o/o) Sex with Men Men & Women lnjection Drugs Fever 75 Serodiscordant Serodiscordant Shared use of Fatigue 68 sexual paftner sexual partner drug injection lnconsistent equipment Myalgia 49 lnconsistent condom use condom use with At risk of sexual Rash 48 during inseftive or a partner whose acquisition of HIV receptive anal sex H lV status is as described for Headache 45 unknown or who is other risk groups Pharyngitis 40 STlwith at high risk chlamydia, Lymphadenopathy 39 themselves gonorrhea, or syphilis within the STI with syphilis or Arthralgia 30 previous 6 months gonorrhea within Night sweats 28 the previous 6 months Diarrhea 27

TABLE 61. Persons at High Risk of HlVAcquisition Who TABLE 62. Signs and Symptoms of Acute HIV lnfection Should be Considered for PrEP" (Acute Retroviral Syndrome) Men Who Have Heterosexual Persons Who Use Sign/Symptom Frequency (o/o) Sex with Men Men & Women lnjection Drugs Fever 75 Serodiscordant Serodiscordant Shared use of Fatigue 68 sexual paftner sexual partner drug injection lnconsistent equipment Myalgia 49 lnconsistent condom use condom use with At risk of sexual Rash 48 during inseftive or a partner whose acquisition of HIV receptive anal sex H lV status is as described for Headache 45 unknown or who is other risk groups Pharyngitis 40 STlwith at high risk chlamydia, Lymphadenopathy 39 themselves gonorrhea, or syphilis within the STI with syphilis or Arthralgia 30 previous 6 months gonorrhea within Night sweats 28 the previous 6 months Diarrhea 27 PrEP = pre-exposure prophylaxis; STI = sexually transmitted infection.

TABLE 61. Persons at High Risk of HlVAcquisition Who TABLE 62. Signs and Symptoms of Acute HIV lnfection Should be Considered for PrEP" (Acute Retroviral Syndrome) Men Who Have Heterosexual Persons Who Use Sign/Symptom Frequency (o/o) Sex with Men Men & Women lnjection Drugs Fever 75 Serodiscordant Serodiscordant Shared use of Fatigue 68 sexual paftner sexual partner drug injection lnconsistent equipment Myalgia 49 lnconsistent condom use condom use with At risk of sexual Rash 48 during inseftive or a partner whose acquisition of HIV receptive anal sex H lV status is as described for Headache 45 unknown or who is other risk groups Pharyngitis 40 STlwith at high risk chlamydia, Lymphadenopathy 39 themselves gonorrhea, or syphilis within the STI with syphilis or Arthralgia 30 previous 6 months gonorrhea within Night sweats 28 the previous 6 months Diarrhea 27 PrEP = pre-exposure prophylaxis; STI = sexually transmitted infection. "Each group is considered at high risk of HIV acquisition if they possess at least fourth-generation antibody and p24 antigen testing may not one of the listed characteristics. Additionally, persons who engage in transactional sex, persons who are trafficked for sex work, men who have sex with men and yet be positive, and diagnosis depends on an HIV viral load women, and transgender women and men who are sexually active can be at high risk of HIV in{ection and should be considered for PrEP based on the criteria test demonstrating HIV RNA. outlined above. Transgender women are at especially high risk. Patients with chronic HIV infection may present with opportunistic infections, especially when CD4 counts are less ritonavir-boosted darunavir or dolutegravir) added to the two- than 2OOl1t"L, meeting the definition for AIDS (see Opportunistic Infections). Even before progression to AIDS, drug PrEP regimen pending results of HIV RNA and viral patients with HIV infection may present with recurrent or resistance testing. The evidence is conflicting concerning severe episodes of infections that do not qualify as opportun potentially increased high-risk behavior and incidence of istic. Other symptoms can result from chronic HIV infection other STIs in PrEP users during therapy. PrEP has also been itselt including lymphadenopathy, fever, night sweats, fatigue, calculated to have favorable cost effectiveness, well below that weight loss, chronic diarrhea, and various oral and skin condi- for other accepted preventive health measures. tions (seborrheic dermatitis, eosinophilic folliculitis, xerosis, KEY POITTS atopic dermatitis, and psoriasis). HIV should also be consid- . Reducing viral load to an undetectable level in blood ered in patients with unexplained cytopenias or nephropathy. reduces the rate of HIV transmission from a sexual part- I(EY POIITS ner to close to zero; "Undetectable = Untransmissible" o Most persons with acute HIV infection are sympto- ("U = U"). matic; however, because symptoms are nonspecific and . Postexposure prophylaxis with a three-drug regimen self-limited, most acute infections are not diagnosed (tenofovir disoproxil fumarate and emtricitabine plus accurately. either raltegravir or dolutegravir) should be started as o During symptomatic acute infection, the fourth- soon as possible after HIV €xpoSUre; it is not recom- generation IgM and IgG antibody and p24 antigen may mended if more than72 hours have passed. not yet be detectable, and diagnosis depends on an HIV o Pre-exposure prophylaxis with two antiretroviral medi- viral load test demonstrating HIV RNA. cations (tenofovir disoproxil fumarate or tenofovir alafenamide, plus emtricitabine) is recommended in \ select persons at high risk for exposure to HIV to reduce Screening and Diagnosis the risk of infection. Testing only symptomatic persons neglects numerous persons who are infected. Thus, the CDC, American College of Physicians, Infectious Diseases Society of America, and Pathophysiology and USPSTF recommend universal screening for HIV in all adults Natural History at least once. The CDC recommends those at higher risk Most persons with acute HIV infection are symptomatic; undergo repeat HIV testing at least annually. In2017, the CDC however, because symptoms are nonspecific and self-limited, reaffirmed its support for this recommendation but noted that most acute infections are not diagnosed accurately. The clinicians can consider the potential benefits of more frequent frequency of signs and symptoms at presentation is shown HIV screening (e.g., every 3 or 6 months) for some asympto- in Table 62. During symptomatic acute infection, the matic sexually active men who have sex with men based on

"Each group is considered at high risk of HIV acquisition if they possess at least fourth-generation antibody and p24 antigen testing may not one of the listed characteristics. Additionally, persons who engage in transactional sex, persons who are trafficked for sex work, men who have sex with men and yet be positive, and diagnosis depends on an HIV viral load women, and transgender women and men who are sexually active can be at high risk of HIV in{ection and should be considered for PrEP based on the criteria test demonstrating HIV RNA. outlined above. Transgender women are at especially high risk. Patients with chronic HIV infection may present with opportunistic infections, especially when CD4 counts are less ritonavir-boosted darunavir or dolutegravir) added to the two- than 2OOl1t"L, meeting the definition for AIDS (see Opportunistic Infections). Even before progression to AIDS, drug PrEP regimen pending results of HIV RNA and viral patients with HIV infection may present with recurrent or resistance testing. The evidence is conflicting concerning severe episodes of infections that do not qualify as opportun potentially increased high-risk behavior and incidence of istic. Other symptoms can result from chronic HIV infection other STIs in PrEP users during therapy. PrEP has also been itselt including lymphadenopathy, fever, night sweats, fatigue, calculated to have favorable cost effectiveness, well below that weight loss, chronic diarrhea, and various oral and skin condi- for other accepted preventive health measures. tions (seborrheic dermatitis, eosinophilic folliculitis, xerosis, KEY POITTS atopic dermatitis, and psoriasis). HIV should also be consid- . Reducing viral load to an undetectable level in blood ered in patients with unexplained cytopenias or nephropathy. reduces the rate of HIV transmission from a sexual part- I(EY POIITS ner to close to zero; "Undetectable = Untransmissible" o Most persons with acute HIV infection are sympto- ("U = U"). matic; however, because symptoms are nonspecific and . Postexposure prophylaxis with a three-drug regimen self-limited, most acute infections are not diagnosed (tenofovir disoproxil fumarate and emtricitabine plus accurately. either raltegravir or dolutegravir) should be started as o During symptomatic acute infection, the fourth- soon as possible after HIV €xpoSUre; it is not recom- generation IgM and IgG antibody and p24 antigen may mended if more than72 hours have passed. not yet be detectable, and diagnosis depends on an HIV o Pre-exposure prophylaxis with two antiretroviral medi- viral load test demonstrating HIV RNA. cations (tenofovir disoproxil fumarate or tenofovir alafenamide, plus emtricitabine) is recommended in \ select persons at high risk for exposure to HIV to reduce Screening and Diagnosis the risk of infection. Testing only symptomatic persons neglects numerous persons who are infected. Thus, the CDC, American College of Physicians, Infectious Diseases Society of America, and Pathophysiology and USPSTF recommend universal screening for HIV in all adults Natural History at least once. The CDC recommends those at higher risk Most persons with acute HIV infection are symptomatic; undergo repeat HIV testing at least annually. In2017, the CDC however, because symptoms are nonspecific and self-limited, reaffirmed its support for this recommendation but noted that most acute infections are not diagnosed accurately. The clinicians can consider the potential benefits of more frequent frequency of signs and symptoms at presentation is shown HIV screening (e.g., every 3 or 6 months) for some asympto- in Table 62. During symptomatic acute infection, the matic sexually active men who have sex with men based on 89

H IV/AIDS HIV -1 /2 anti gen/anti body combination immu noassay (+) (-) Negative for HIV-1 and HIV-2 antibodies and p24 antigena HIV-1/HlV-2 antibody differentiation immunoassay HIV-1 (+) Hrv-1 (-) HIV-1 (+) Htv_1 (-) Hrv-2 (-) HIV-2 (+) HIV-2 (+) or indeterminate HIV-1 antibodies detectedb HIV-2 antibodies detected' HIV antibodies detectedd Hlv_2 (_) HIV-1 NAAT HIV NAAT(+) HIV NAAT(-) Acute HIV-1 infection Negative for HIV-1e FIGURE 36. CDC-recommendedalgorithmforlaboratoryHlVtesting.NAAT=nucleicacidamplificationtest.(+)indicatesreactivetestresult.(-)indicatesn0nreactive test result. uNo evidence of HIV infection. bHlV-'l infection. 'HlV.2 infection. dHlV-1 and HIV-2 infection. 'HlV-1 /2 antigen/antibody combination immunoassay result was a false positive.

FIGURE 36. CDC-recommendedalgorithmforlaboratoryHlVtesting.NAAT=nucleicacidamplificationtest.(+)indicatesreactivetestresult.(-)indicatesn0nreactive test result. uNo evidence of HIV infection. bHlV-'l infection. 'HlV.2 infection. dHlV-1 and HIV-2 infection. 'HlV-1 /2 antigen/antibody combination immunoassay result was a false positive. their individual risk factors, local HIV epidemiolos/, and local management expertise. Initial evaluation should include com- policies. plete history (including social and sexual) and examination for The fourth-generation HIV testing uses a combination assay signs and symptoms of opportunistic infection or other compli- for HIV antibody and HIV p24 antigen, which detects acute infec cations. Patient education and counseling should include infor- tion 15 to 20 days after the onset of infection. The testing algo mation on transmission and prevention. Initial laboratory tests rithm is outlined in Figure 36. In chronic infection, the initial include baseline organ function and evaluation for other infec combination assay is nearly 100'1, sensitive and specific, but test- tions with higher prevalence in persons with HIV (T'atrte 63). A ing in low prevalence populations (such as general screening) can baseline CD4 cell count guides opportunistic infection pro- still result in false positives, so waiting for the results of the con- phylaxis, and a baseline viral load supports monitoring ART firmatory antibody differentiation immunoassay or nucleic acid effectiveness (see Management of HIV Infection). amplification testing is important for a definitive diagnosis.

their individual risk factors, local HIV epidemiolos/, and local management expertise. Initial evaluation should include com- policies. plete history (including social and sexual) and examination for The fourth-generation HIV testing uses a combination assay signs and symptoms of opportunistic infection or other compli- for HIV antibody and HIV p24 antigen, which detects acute infec cations. Patient education and counseling should include infor- tion 15 to 20 days after the onset of infection. The testing algo mation on transmission and prevention. Initial laboratory tests rithm is outlined in Figure 36. In chronic infection, the initial include baseline organ function and evaluation for other infec combination assay is nearly 100'1, sensitive and specific, but test- tions with higher prevalence in persons with HIV (T'atrte 63). A ing in low prevalence populations (such as general screening) can baseline CD4 cell count guides opportunistic infection pro- still result in false positives, so waiting for the results of the con- phylaxis, and a baseline viral load supports monitoring ART firmatory antibody differentiation immunoassay or nucleic acid effectiveness (see Management of HIV Infection). amplification testing is important for a definitive diagnosis. KEY POITTS lmmunizations and Prophylaxis for o It is recommended that all adults be tested for HIV Opportu nistic I nfections Numerous immunizations are recommended for all persons infection at least once. with HIV starting with the l3-valent pneumococcal conjugate . The fourth-generation HIV testing uses a combination and 23-valent pneumococcal polysaccharide vaccines, respec- assay for HIV antibody and HIV p24 antigen and is nearly tively, at least B weeks apart; a 23-valent polysaccharide vac- 100'/. sensitive and specific for chronic HIV infection. cine booster is also recommended after 5 years. Patients who are not already immune or infected with HBV should receive the hepatitis B vaccine series. Influenza, COVID-19, tetanus- lnitiation of Care diphtheria-pertussis, hepatitis A, and human papillomavirus lnitial Evaluation and Laboratory Testing vaccinations are indicated as for the general population. All persons who test positive for HIV should immediately be Measles-mumps-rubella, varicella, and recombinant zoster referred to a health care provider with HIV infection vaccines can be given as long as the CD4 cell count is greater

KEY POITTS lmmunizations and Prophylaxis for o It is recommended that all adults be tested for HIV Opportu nistic I nfections Numerous immunizations are recommended for all persons infection at least once. with HIV starting with the l3-valent pneumococcal conjugate . The fourth-generation HIV testing uses a combination and 23-valent pneumococcal polysaccharide vaccines, respec- assay for HIV antibody and HIV p24 antigen and is nearly tively, at least B weeks apart; a 23-valent polysaccharide vac- 100'/. sensitive and specific for chronic HIV infection. cine booster is also recommended after 5 years. Patients who are not already immune or infected with HBV should receive the hepatitis B vaccine series. Influenza, COVID-19, tetanus- lnitiation of Care diphtheria-pertussis, hepatitis A, and human papillomavirus lnitial Evaluation and Laboratory Testing vaccinations are indicated as for the general population. All persons who test positive for HIV should immediately be Measles-mumps-rubella, varicella, and recombinant zoster referred to a health care provider with HIV infection vaccines can be given as long as the CD4 cell count is greater 90