2008 Guidelines for 2008 Guidelines for Prevention and Treatment of Prevention and Treatment of Opportunistic Infections in Opportunistic Infections in

HIV-Infected Adults and HIV-Infected Adults and Adolescents : Part 1Adolescents : Part 1

Major Changes Since 2008Major Changes Since 2008

(1) more emphasis on the importance of ART (1) more emphasis on the importance of ART for prevention and treatment of OIs, for prevention and treatment of OIs, especially those for which specific especially those for which specific chemoprophylaxis and treatment do not exist; chemoprophylaxis and treatment do not exist; (2) information on diagnosis and (2) information on diagnosis and management of immune reconstitution management of immune reconstitution inflammatory syndromes (IRIS); inflammatory syndromes (IRIS); (3) information on interferon-gamma release (3) information on interferon-gamma release assays (IGRAs) for the detection of latent assays (IGRAs) for the detection of latent Mycobacterium tuberculosis infection; Mycobacterium tuberculosis infection;

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Major Changes Since 2008Major Changes Since 2008

(4) updated information on drug (4) updated information on drug interactions affecting use of rifamycin interactions affecting use of rifamycin drugs for prevention and treatment of drugs for prevention and treatment of tuberculosis (TB); tuberculosis (TB);

(5) the addition of a section on hepatitis B (5) the addition of a section on hepatitis B virus (HBV) infection;virus (HBV) infection;

(6) the addition of a section on malaria to (6) the addition of a section on malaria to the OIs of geographic interest. the OIs of geographic interest.

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Initiation of ART in the Setting of Initiation of ART in the Setting of an Acute OI (Treatment-Naïve an Acute OI (Treatment-Naïve

Patients) Patients) No consensus has been reached No consensus has been reached concerning the optimal time to start ART in concerning the optimal time to start ART in the setting of a recently diagnosed OI. the setting of a recently diagnosed OI.

Recently completed RCT demonstrated a Recently completed RCT demonstrated a clinical and survival benefit of starting ART clinical and survival benefit of starting ART early, within the first 2 weeks, of initiation early, within the first 2 weeks, of initiation of treatment for an acute OI, excluding TB of treatment for an acute OI, excluding TB

Zolopa A, et al., ACTG A5164. 15th CROI; 2008; Boston, MA. Abstract 142. 4

Initiation of ART in the Setting of Initiation of ART in the Setting of an Acute OI (Treatment-Naïve an Acute OI (Treatment-Naïve

Patients) Patients) Majority of OIs represented were PCP and Majority of OIs represented were PCP and serious bacterial infectionsserious bacterial infections

Study ConclusionStudy Conclusion– Unless there are other contraindications, early Unless there are other contraindications, early

initiation of ART near the time of initiation of initiation of ART near the time of initiation of OI treatment should be considered for most OI treatment should be considered for most patients with an acute OI, excluding TB.patients with an acute OI, excluding TB.

Zolopa A, et al., ACTG A5164. 15th CROI; 2008; Boston, MA. Abstract 142. 5

Initiation of ART in the Setting of Initiation of ART in the Setting of an Acute OI (Treatment-Naïve an Acute OI (Treatment-Naïve

Patients) Patients) In cases of cryptosporidiosis, In cases of cryptosporidiosis, microsporidiosis, PML, KS, PCP, and microsporidiosis, PML, KS, PCP, and serious bacterial infections, the early serious bacterial infections, the early benefits of ART outweigh increased risk benefits of ART outweigh increased risk related to these other factors and ART related to these other factors and ART should be started as soon as possibleshould be started as soon as possible

Risks of early ART initiation may be greatest Risks of early ART initiation may be greatest in those with CNS IRIS leading to increased in those with CNS IRIS leading to increased ICP and brain shift (WCM opinion) ICP and brain shift (WCM opinion)

Zolopa A, et al., ACTG A5164. 15th CROI; 2008; Boston, MA. Abstract 142. 6

Management of Acute OIs in Management of Acute OIs in Patients Receiving ART: 3 Patients Receiving ART: 3

Groups Groups OIs that occur shortly after initiating ART (within 12 OIs that occur shortly after initiating ART (within 12 weeks). weeks). – ““unmasking” IRISunmasking” IRIS– Treat OI and continue ARTTreat OI and continue ART

OIs occurring >12 weeks after initiation of ART among OIs occurring >12 weeks after initiation of ART among patients with suppressed pVL and CD4+ >200 cells/μLpatients with suppressed pVL and CD4+ >200 cells/μL– IRIS vs incomplete immune restorationIRIS vs incomplete immune restoration– Continue ARTContinue ART– No evidence that changing the ART regimen in this setting No evidence that changing the ART regimen in this setting

will improve the CD4+ response will improve the CD4+ response

OIs that develop in setting of virologic and OIs that develop in setting of virologic and immunologic failure while on potent ARTimmunologic failure while on potent ART– Treat OITreat OI– HIV resistance testing and regimen change HIV resistance testing and regimen change

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Special Considerations During Special Considerations During Pregnancy Pregnancy

For pregnant women who have had an OI For pregnant women who have had an OI diagnosed and are not on ART, immediate diagnosed and are not on ART, immediate initiation of ART with OI therapy should be initiation of ART with OI therapy should be encouraged to minimize the risk of perinatal encouraged to minimize the risk of perinatal transmission of HIV.transmission of HIV.Decisions about immediate versus delayed Decisions about immediate versus delayed initiation of ART in pregnancy should take initiation of ART in pregnancy should take into account gestational age, maternal HIV into account gestational age, maternal HIV RNA levels and clinical condition, and RNA levels and clinical condition, and potential toxicities and interactions between potential toxicities and interactions between ART and OI drugs. ART and OI drugs.

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Pneumocystis PneumoniaPneumocystis Pneumonia

EpidemiologyEpidemiology– 90% of cases with CD4+ counts of <200 cells/μL90% of cases with CD4+ counts of <200 cells/μL– Other risk factorsOther risk factors

CD4+ cell percentage <14%CD4+ cell percentage <14%previous episodes of PCP previous episodes of PCP oral thrushoral thrushrecurrent bacterial pneumonia recurrent bacterial pneumonia unintentional weight lossunintentional weight losshigher plasma HIV RNA higher plasma HIV RNA

– Mortality 20%–40% with profound Mortality 20%–40% with profound immunosuppression immunosuppression

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Pneumocystis PneumoniaPneumocystis Pneumonia

Clinical ManifestationsClinical Manifestations– subacute onset of progressive dyspnea, fever, subacute onset of progressive dyspnea, fever,

nonproductive cough, and chest discomfortnonproductive cough, and chest discomfort– Chest clear or “cellophane” ralesChest clear or “cellophane” rales– Oxygenation variableOxygenation variable– LDH >500 mg/dL is common but nonspecific LDH >500 mg/dL is common but nonspecific

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Pneumocystis PneumoniaPneumocystis Pneumonia

– CXR typically bilateral interstitial infiltrates or normal CXR typically bilateral interstitial infiltrates or normal (if mild)(if mild)

– Atypical presentations: nodules, blebs and cysts, Atypical presentations: nodules, blebs and cysts, asymmetric disease, upper lobe localization, and asymmetric disease, upper lobe localization, and pneumothorax occur. pneumothorax occur.

– Pneumothorax in a patient with HIV infection should Pneumothorax in a patient with HIV infection should raise the suspicion of PCP raise the suspicion of PCP

– Cavitation, intrathoracic adenopathy, and pleural Cavitation, intrathoracic adenopathy, and pleural effusion are uncommon effusion are uncommon

presence might indicate an alternative diagnosis. presence might indicate an alternative diagnosis. – Approximately 13%–18% of patients with documented Approximately 13%–18% of patients with documented

PCP have another concurrent cause of pulmonary PCP have another concurrent cause of pulmonary dysfunction (e.g., TB, KS, or bacterial pneumonia) dysfunction (e.g., TB, KS, or bacterial pneumonia)

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Mild Pneumocystis Pneumonia

PCP

Severe Pneumocystis Pneumonia

Residual Cyst 6 weeks after Rx of PCP

Pneumocystis Pneumonia: Pneumocystis Pneumonia: DiagnosisDiagnosis

Expectorated sputum not usefulExpectorated sputum not usefulSensitivity ofSensitivity of– induced sputum <50%–>90%induced sputum <50%–>90%– bronchoalveolar lavage 90%–99% bronchoalveolar lavage 90%–99% – transbronchial biopsy 95%–100%transbronchial biopsy 95%–100%– open lung biopsy 95%–100%open lung biopsy 95%–100%

MethodsMethods– Giemsa, Diff-Quik, and Wright stainsGiemsa, Diff-Quik, and Wright stains– Gomori methenamine silver (GMS)Gomori methenamine silver (GMS)– IFAIFA– PCR sensitive but not specificPCR sensitive but not specific

OtherOther– S-adenosylmethionine (which is lowered in cases of active PCP) S-adenosylmethionine (which is lowered in cases of active PCP) – (1→3)ß-D-glucan (levels increase with PCP) (1→3)ß-D-glucan (levels increase with PCP)

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Geimsa: leftGMS: below

Pneumocystis Pneumonia: Pneumocystis Pneumonia: TreatmentTreatment

Initiate presumptive treatment without delayInitiate presumptive treatment without delayTMP-SMX is the treatment of choice TMP-SMX is the treatment of choice Adjunctive corticosteroids Adjunctive corticosteroids – pOpO2 2 <70 mm Hg or Aa O<70 mm Hg or Aa O2 2 gradient >35 mm Hg RA gradient >35 mm Hg RA

within 72 hours of starting PCP treatmentwithin 72 hours of starting PCP treatment– Reduce Mortality about 50%Reduce Mortality about 50%– ““Rescue” steroids (after 72 h) of uncertain benefitRescue” steroids (after 72 h) of uncertain benefit

Ventilatory supportVentilatory support– survival in up to 50% requiring ventilatory supportsurvival in up to 50% requiring ventilatory support

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Pneumocystis Pneumonia: Pneumocystis Pneumonia: TreatmentTreatment

Many health care providers delay initiation Many health care providers delay initiation of ART until after the completion of anti-of ART until after the completion of anti-PCP therapy, or until at least 2 weeks after PCP therapy, or until at least 2 weeks after initiating anti-PCP therapyinitiating anti-PCP therapy– Additive/synergistic toxicitiesAdditive/synergistic toxicities– Rare IRISRare IRIS

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Pneumocystis Pneumonia: Pneumocystis Pneumonia: Treatment FailureTreatment Failure

Important to wait at least 4–8 days before Important to wait at least 4–8 days before switching therapy for lack of clinical switching therapy for lack of clinical improvement improvement In the absence of corticosteroid therapy, early and In the absence of corticosteroid therapy, early and reversible deterioration within the first 3–5 days of reversible deterioration within the first 3–5 days of therapy is typicaltherapy is typicalFailure due to lack of drug efficacy occurs in Failure due to lack of drug efficacy occurs in approximately 10% of those with mild-to-moderate approximately 10% of those with mild-to-moderate disease disease Other concomitant infections must be excluded (BAL)Other concomitant infections must be excluded (BAL)use parenteral pentamidine or primaquine combined use parenteral pentamidine or primaquine combined with clindamycin for moderate-severe diseasewith clindamycin for moderate-severe disease

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Pneumocystis Pneumonia: Toxicity Pneumocystis Pneumonia: Toxicity ManagementManagement

Treatment-limiting toxicities occurs in up to Treatment-limiting toxicities occurs in up to one-third of patientsone-third of patients TMP-SulfaTMP-Sulfa– rash (30%–55%) (including SJS)rash (30%–55%) (including SJS)– fever (30%–40%) fever (30%–40%) – leukopenia (30%–40%) leukopenia (30%–40%) – thrombocytopenia (15%) thrombocytopenia (15%) – azotemia (1%–5%) azotemia (1%–5%) – hepatitis (20%)hepatitis (20%)– hyperkalemia. hyperkalemia.

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Pneumocystis Pneumonia: Toxicity Pneumocystis Pneumonia: Toxicity ManagementManagement

Pentamidine (IV)Pentamidine (IV)– azotemia, pancreatitis, hypo- or azotemia, pancreatitis, hypo- or

hyperglycemia, leukopenia, electrolyte hyperglycemia, leukopenia, electrolyte abnormalities,hypotension during infusion, abnormalities,hypotension during infusion, and cardiac dysrhythmiaand cardiac dysrhythmia

Dapsone and PrimaquineDapsone and Primaquine– Hemolysis with G6PD deficiencyHemolysis with G6PD deficiency– MethemoglobinemiaMethemoglobinemia

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Pneumocystis PreventionPneumocystis Prevention

Primary prophylaxisPrimary prophylaxis– CD4+ count of <200 cells/μL or a history of oropharyngeal CD4+ count of <200 cells/μL or a history of oropharyngeal

candidiasis candidiasis – CD4+ cell percentage of <14% or a history of an AIDS-defining CD4+ cell percentage of <14% or a history of an AIDS-defining

illnessillness– Discontinuing primary prophylaxisDiscontinuing primary prophylaxis

response to ART with increase CD4+ counts to >200 cells/μL for >3 response to ART with increase CD4+ counts to >200 cells/μL for >3 months months reintroduced if the CD4+ count decreases to <200 cells/μL reintroduced if the CD4+ count decreases to <200 cells/μL

Secondary prophylaxisSecondary prophylaxis– chronic maintenance therapy with TMP-SMX unless immune chronic maintenance therapy with TMP-SMX unless immune

reconstitution occurs as a result of ART reconstitution occurs as a result of ART – discontinued when CD4+ count increased from <200 cells/μL to discontinued when CD4+ count increased from <200 cells/μL to

>200 cells/μL for >3 months as a result of ART >200 cells/μL for >3 months as a result of ART – If the episode occurred at a CD4+ count of ≥200 cells/μL, If the episode occurred at a CD4+ count of ≥200 cells/μL,

continue PCP prophylaxis for life continue PCP prophylaxis for life

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Primary Prophylaxis: PCPPrimary Prophylaxis: PCP

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Toxoplasma gondii EncephalitisToxoplasma gondii Encephalitis

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Toxoplasma Encephalitis (TE)Toxoplasma Encephalitis (TE)

EpidemiologyEpidemiology– Seroprevalence 15% in the United States and Seroprevalence 15% in the United States and

50%–75% in certain European countries 50%–75% in certain European countries – Greatest risk with a CD4+ count <50 cells/μLGreatest risk with a CD4+ count <50 cells/μL– Rare if CD4>200Rare if CD4>200– 12 month incidence if not receiving 12 month incidence if not receiving

prophylaxis with drugs active against prophylaxis with drugs active against T. gondii T. gondii approximately 33%approximately 33%

– incidence of toxoplasmosis in patients who are incidence of toxoplasmosis in patients who are seronegative for seronegative for Toxoplasma is extremely low Toxoplasma is extremely low

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TE: Clinical ManifestationsTE: Clinical Manifestations

Focal encephalitis with headache, Focal encephalitis with headache, confusion, or motor weakness and feverconfusion, or motor weakness and fever

CT scan or MRI of the brain will typically CT scan or MRI of the brain will typically show multiple contrast-enhancing lesions, show multiple contrast-enhancing lesions, often with associated edema often with associated edema

Can manifest as single lesions, especially Can manifest as single lesions, especially by CT by CT

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TE: DiagnosisTE: Diagnosis

Almost uniformly seropositive for anti-Almost uniformly seropositive for anti-toxoplasma IgG in serumtoxoplasma IgG in serum

Absence of IgG antibody makes a diagnosis of Absence of IgG antibody makes a diagnosis of toxoplasmosis unlikely but not impossibletoxoplasmosis unlikely but not impossible

Detection of Detection of T. gondii by PCR in CSF T. gondii by PCR in CSF disappointing disappointing – Specificity is high (96%–100%), Specificity is high (96%–100%), – Sensitivity is low (50%) and the Sensitivity is low (50%) and the – Usually negative once specific anti-toxoplasma Usually negative once specific anti-toxoplasma

therapy started therapy started 28

TE: Differential DiagnosisTE: Differential Diagnosis

Primary CNS lymphomaPrimary CNS lymphoma– CD4 < 50CD4 < 50

TuberculomasTuberculomasFungal infection (e.g., cryptococcosis) Fungal infection (e.g., cryptococcosis) Chagas disease Chagas disease Bacterial abscess Bacterial abscess rarely PML (inflammatory form)rarely PML (inflammatory form)Neurocysticercosis Neurocysticercosis

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TE: PreventionTE: Prevention

PrimaryPrimary– test for IgG antibody to test for IgG antibody to Toxoplasma soon after the Toxoplasma soon after the

diagnosis of HIV infection to detect latent infection diagnosis of HIV infection to detect latent infection with T. gondii with T. gondii

– advise not to eat raw or undercooked meat, advise not to eat raw or undercooked meat, including undercooked lamb, beef, pork, or venison including undercooked lamb, beef, pork, or venison

– avoid cat litteravoid cat litter– Toxoplasma-seropositive patients who have a Toxoplasma-seropositive patients who have a

CD4+ count of <100 cells/μL should be CD4+ count of <100 cells/μL should be administered prophylaxis against TE (TMP-SMX)administered prophylaxis against TE (TMP-SMX)

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TE: PreventionTE: Prevention

Discontinuing Primary ProphylaxisDiscontinuing Primary Prophylaxis– patients who have responded to ART with patients who have responded to ART with

an increase in CD4+ counts to >200 an increase in CD4+ counts to >200 cells/μL for >3 monthscells/μL for >3 months

– reintroduced if the CD4+ count decreases reintroduced if the CD4+ count decreases to <100–200 cells/μL to <100–200 cells/μL

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TE: Primary ProphylaxisTE: Primary Prophylaxis

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TE: TreatmentTE: Treatment

Initial therapy of choice for TE consists of Initial therapy of choice for TE consists of the combination of pyrimethamine plus the combination of pyrimethamine plus sulfadiazine plus leucovorin sulfadiazine plus leucovorin Some treat severely ill patients initially Some treat severely ill patients initially requiring parenteral therapy for TE with requiring parenteral therapy for TE with parenteral TMP-SMX (oral pyrimethamine parenteral TMP-SMX (oral pyrimethamine could be considered in addition to IV TMP-could be considered in addition to IV TMP-SMX) or oral pyrimethamine plus SMX) or oral pyrimethamine plus parenteral clindamycin parenteral clindamycin

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TE: TreatmentTE: Treatment

Acute therapy for TE should be Acute therapy for TE should be continued for at least 6 weeks, if there continued for at least 6 weeks, if there is clinical and radiologic improvement is clinical and radiologic improvement

Adjunctive corticosteroids Adjunctive corticosteroids (dexamethasone) only for treatment of (dexamethasone) only for treatment of a mass effect or associated edemaa mass effect or associated edema

Anticonvulsants should not be Anticonvulsants should not be administered as prophylactics to all administered as prophylactics to all patients patients

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TE: Treatment and MaintenanceTE: Treatment and Maintenance

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TE: Treatment FailureTE: Treatment Failure

A brain biopsy should be strongly A brain biopsy should be strongly considered for patients who fail to considered for patients who fail to respond to initial therapy for TErespond to initial therapy for TE– defined by clinical or radiologic defined by clinical or radiologic

deterioration during the first week despite deterioration during the first week despite adequate therapy OR adequate therapy OR

– lack of clinical improvement within 2 lack of clinical improvement within 2 weeks. weeks.

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Cerebral toxoplasmosis

Cerebral Toxoplasmosis

TE: Secondary ProphylaxisTE: Secondary Prophylaxis

Pyrimethamine plus sulfadiazine plus Pyrimethamine plus sulfadiazine plus leucovorin is highly effective as leucovorin is highly effective as suppressive therapy for patients with TEsuppressive therapy for patients with TE

For sulfa intolerant patients, For sulfa intolerant patients, pyrimethamine plus clindamycinpyrimethamine plus clindamycin

TMP-SMX could be used as a suppressive TMP-SMX could be used as a suppressive regimen to reduce pill burdenregimen to reduce pill burden11

401. Duval, X et al., AIDS, 2004. 18(9): p. 1342-4.

TE: Secondary ProphylaxisTE: Secondary Prophylaxis

Discontinuing maintenance therapyDiscontinuing maintenance therapy– Consider if sustained increase in their CD4+ Consider if sustained increase in their CD4+

counts of >200 cells/μL after ART (e.g., >6 counts of >200 cells/μL after ART (e.g., >6 months) months)

– Reintroduced if the CD4+ count decreases to Reintroduced if the CD4+ count decreases to <200 cells/μL <200 cells/μL

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Disseminated Disseminated Mycobacterium Mycobacterium avium avium Complex (dMAC)Complex (dMAC)

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dMAC: EpidemiologydMAC: Epidemiology

Ubiquitous in the environment Ubiquitous in the environment The mode of transmission: inhalation, ingestion, or The mode of transmission: inhalation, ingestion, or inoculation via the respiratory or gastrointestinal tractinoculation via the respiratory or gastrointestinal tractMAC disease generally occurs among persons with MAC disease generally occurs among persons with CD4+ counts <50 cells/μL (20-40%)CD4+ counts <50 cells/μL (20-40%)Overall incidence rate 2 cases per 100 person-years Overall incidence rate 2 cases per 100 person-years among those withamong those with– CD4+ count <100 cells/μL receiving effective prophylaxis CD4+ count <100 cells/μL receiving effective prophylaxis

oror– have responded to ART with a sustained increase in have responded to ART with a sustained increase in

CD4+ count to levels >100–200 cells/μLCD4+ count to levels >100–200 cells/μL

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dMAC: Clinical ManifestationsdMAC: Clinical Manifestations

No ARTNo ART– Disseminated, multi-organ, mycobacteremiaDisseminated, multi-organ, mycobacteremia– Fever, night sweats, weight loss, fatigue, Fever, night sweats, weight loss, fatigue,

diarrhea, and abdominal paindiarrhea, and abdominal pain

On ARTOn ART– Localized (cervical or mesenteric Localized (cervical or mesenteric

lymphadenitis, pneumonitis, pericarditis, lymphadenitis, pneumonitis, pericarditis, osteomyelitis, skin or soft tissue abscesses, osteomyelitis, skin or soft tissue abscesses, genital ulcers, or CNS infection) genital ulcers, or CNS infection)

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dMAC: Clinical ManifestationsdMAC: Clinical Manifestations

DisseminatedDisseminated– AnemiaAnemia– Increased alkaline phosphataseIncreased alkaline phosphatase– HepatomegalyHepatomegaly– SplenomegalySplenomegaly– LymphadenopathyLymphadenopathy

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MAC IRISMAC IRIS

Focal lymphadenitis with feverFocal lymphadenitis with fever

Absent mycobacteremiaAbsent mycobacteremia

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dMAC: DiagnosisdMAC: Diagnosis

Isolation of MAC from cultures of blood, Isolation of MAC from cultures of blood, lymph node, bone marrow, or other lymph node, bone marrow, or other normally sterile tissue or body fluidsnormally sterile tissue or body fluids

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dMAC: Small BoweldMAC: Small Bowel

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dMAC IRISdMAC IRIS

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dMAC: PreventiondMAC: Prevention

Chemoprophylaxis against disseminated Chemoprophylaxis against disseminated MAC disease if CD4+ count of <50 MAC disease if CD4+ count of <50 cells/μLcells/μL

Primary MAC prophylaxis should be Primary MAC prophylaxis should be discontinued when response to ART with discontinued when response to ART with an increase in CD4+ counts to >100 an increase in CD4+ counts to >100 cells/μL for ≥3 monthscells/μL for ≥3 months

Reintroduced if the CD4+ count decreases Reintroduced if the CD4+ count decreases to <50 cells/μLto <50 cells/μL

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dMAC: PreventiondMAC: Prevention

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dMAC: TreatmentdMAC: Treatment

Two or more antimycobacterial drugs to Two or more antimycobacterial drugs to prevent or delay the emergence of resistanceprevent or delay the emergence of resistanceClarithromycin is the preferred first agentClarithromycin is the preferred first agent– Azithromycin can be substituted for clarithromycin Azithromycin can be substituted for clarithromycin

for drug interactions or clarithromycin intolerancefor drug interactions or clarithromycin intolerance– Azithromycin should be used in pregnancyAzithromycin should be used in pregnancy

EMB is the recommended second drug EMB is the recommended second drug Some clinicians would add rifabutin as a third Some clinicians would add rifabutin as a third drugdrug

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dMAC: TreatmentdMAC: Treatment

A third or fourth drug considered in settings in A third or fourth drug considered in settings in which mortality is increased and emergence which mortality is increased and emergence of drug resistance is most likelyof drug resistance is most likely– advanced immunosuppression (CD4+ count <50 advanced immunosuppression (CD4+ count <50

cells/μL), cells/μL), – high mycobacterial loads (>2 loghigh mycobacterial loads (>2 log10 10 colony forming colony forming

units/mL of blood), orunits/mL of blood), or– absence of effective ART absence of effective ART

Based on data in non-HIV-infected patients, Based on data in non-HIV-infected patients, the third or fourth drug might include an the third or fourth drug might include an injectable agent such as amikacin or injectable agent such as amikacin or streptomycinstreptomycin

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dMAC TreatmentdMAC Treatment

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dMAC: MonitoringdMAC: Monitoring

A repeat blood culture for MAC 4–8 weeks A repeat blood culture for MAC 4–8 weeks after initiation of therapy after initiation of therapy onlyonly for patients for patients who fail to have a clinical responsewho fail to have a clinical responseImprovement in fever and a decline of Improvement in fever and a decline of mycobacteria in blood or tissue can be mycobacteria in blood or tissue can be expected within 2–4 weeksexpected within 2–4 weeksFor those with more extensive disease or For those with more extensive disease or advanced immunosuppression, clinical advanced immunosuppression, clinical response might be delayed.response might be delayed.

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dMAC: IRISdMAC: IRIS

Symptoms of moderate-to-severe intensity Symptoms of moderate-to-severe intensity due to IRIS in the setting of ART should due to IRIS in the setting of ART should receive initial treatment with nonsteroidal, receive initial treatment with nonsteroidal, anti-inflammatory agentsanti-inflammatory agentsIf IRIS symptoms fail to improve, short-If IRIS symptoms fail to improve, short-term (4–8 weeks) systemic corticosteroid term (4–8 weeks) systemic corticosteroid therapy, in doses equivalent to 20–40 mg therapy, in doses equivalent to 20–40 mg of oral prednisone daily, has been of oral prednisone daily, has been successful in reducing symptoms and successful in reducing symptoms and morbiditymorbidity

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dMAC: Treatment FailuredMAC: Treatment Failure

Two new drugs to which the isolate is Two new drugs to which the isolate is susceptible: EMB, rifabutin, amikacin, or a susceptible: EMB, rifabutin, amikacin, or a quinolone (moxifloxacin, ciprofloxacin, or quinolone (moxifloxacin, ciprofloxacin, or levofloxacin)levofloxacin)

An injectable agent such as amikacin or An injectable agent such as amikacin or streptomycin should be consideredstreptomycin should be considered

Optimizing ART is an important adjunct to Optimizing ART is an important adjunct to second-line or salvage therapy for MAC diseasesecond-line or salvage therapy for MAC disease

Clofazimine should not be usedClofazimine should not be used

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dMAC: Therapy DurationdMAC: Therapy Duration

Lifelong secondary prophylaxis (chronic Lifelong secondary prophylaxis (chronic maintenance therapy) (AII), unless immune maintenance therapy) (AII), unless immune reconstitution occurs as a result of ARTreconstitution occurs as a result of ARTDiscontinuing chronic maintenance therapy is Discontinuing chronic maintenance therapy is reasonable ifreasonable if– completed a treatment course of ≥12 monthscompleted a treatment course of ≥12 months– asymptomatic with respect to MACasymptomatic with respect to MAC– sustained increase (≥6 months) CD4+ to >100sustained increase (≥6 months) CD4+ to >100

Secondary prophylaxis reintroduced if the Secondary prophylaxis reintroduced if the CD4+ count decreases to <100 cells/μLCD4+ count decreases to <100 cells/μL

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