IRIS treatment - Treat the OI - Mild disease: use ___ for fever and pain; use ___ for any bronchospasms - Severe disease: ___ 1-2 mg/kg (or equivalent) daily for 1-2 weeks, followed by a taper) - Avoid steroids in ___ meningitis or ___ ___ due to worse outcomes

- NSAIDs, ICS - prednisone - cryptococcal, Kaposi's sarcoma

OI Flashcards by Reagan Smith

Without treatment, virtually all individuals infected with HIV eventually
develop severe immunodeficiency due to ___cell depletion (↓cell-mediated immunity) making the patient susceptible to infection by
intracellular pathogens, fungi, and viruses with decreased protection
against ___ and decreased ___ formation

CD4
cancer
antibody

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Normal CD4 counts in adults

800-1200 cells/mm3

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During HIV infection, a progressive depletion in CD4 cells is observed,
with an average decline of ___ - ___ cells/year without antiretroviral therapy

50-100

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CD4 counts ____ cells/mm3, and especially ____ cells/mm3 are associated with the development of OIs

< 500
< 200

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Infection Risk & CD4 Count

___ , ___ , and ___ can occur at any CD4 cell count
CD4 count < ___ cells/mm3: candidiasis and leukoplakia
CD4 count < ___ cells/mm3: PJP, CMV retinitis, toxoplasmosis, MAC, cryptococcus meningitis or diarrhea, lymphomas, and Kaposi’s sarcoma
Tuberculosis and syphilis can __ HIV viral load leading to __ risk of viral transmission and progression

Mycobacterium TB, pneumonias, and dermatomal Varicella zoster
500
200
⬆,⬆

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Primary vs. Secondary Prophylaxis for OIs

Primary prophylaxis: administration of an anti-infective agent to prevent the ___ episode of a particular OI in a patient living with HIV when they are at risk for developing that OI based on their CD4 count
Secondary Prophylaxis ( ___ maintenance or suppressive
therapy): administration of anti-infective therapy to prevent ___ of a particular OI in a patient living with HIV after they have been successfully treated for that OI and remain at risk for developing that OI based on their CD4 cell count

1st
chronic
recurrences

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When to Start ART in the Setting of an Acute Opportunistic Infection

Initiation of ART during an acute OI is very useful when effective OI therapy is ___ ___
1. Progressive multifocal leukoencephalopathy (PML),
cryptosporidiosis, & Kaposi’s sarcoma
2. Improvement in ___ function from ART will help with the resolution of these OIs

not available
immune

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When to Start ART in the Setting of an Acute Opportunistic Infection

In contrast, for other OIs, there are several disadvantages of immediately
starting ART in the setting of an acute OI
- potential development of ___
- Characterized by fever, inflammation, and worsening clinical manifestations of the OI
- can be seen during the acute treatment of MAC, TB, PJP, toxoplasmosis, Hepatitis B & C, CMV, cryptococcus, histoplasmosis, and varicella zoster infections

also DI’s between ART and OI therapy and additive drug toxicities

IRIS

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IRIS

More likely to occur in patients with low CD4 cell counts (< __ cells/mm3) and high HIV RNA levels (> ___ copies/mL)
If it happens, it is most common within the first ___ - ___of ART

Most clinicians wait for a clinical response to OI therapy, usually __ weeks, before initiating ART
- Exception: Start ART within 2 weeks of starting ___ treatment if CD4 count < 50 cells/mm3 or within 8 weeks if CD4 count is higher

50,
100,000
4-8 weeks
2 weeks
TB

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IRIS treatment

Treat the OI
Mild disease: use ___ for fever and pain; use ___ for any bronchospasms
Severe disease: ___ 1-2 mg/kg (or equivalent) daily for 1-2 weeks, followed by a taper)
Avoid steroids in ___ meningitis or ___ ___ due to worse outcomes

NSAIDs, ICS
prednisone
cryptococcal, Kaposi’s sarcoma

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Oropharyngeal Candidiasis – thrush

Preferred Treatment: ___ 200 mg loading dose, followed by 100-200 mg PO daily for ___- ___ days
- As effective or superior to topical therapy
- More convenient and better tolerated

Alternative:
- ___ agents for initial, mild to moderate episodes only
- Advantages: reduces systemic drug exposure, diminishes the risk of DDIs and SEs, and decreases risk of resistance
- Disadvantages: use impacted by unpleasant taste, GI SEs and multiple daily dosing

fluconazole, 7-14 days
topical

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Topical Agents Used in the Treatment of Oropharyngeal Candidiasis

___ Suspension (100,000 units/mL): 5 mL swish and swallow ___ x 7-14 days
- Should be thoroughly rinsed in mouth and retained in mouth for as long as possible before ___

___ Troches (10 mg lozenge): 10 mg oral lozenge __ times daily for 7-14 days
- Should be dissolved slowly in the
mouth over 15-30 minutes

can also do miconazole buccal tab, itraconazole solution, or posaconazole suspension

Nystatin
QID
swallowing
Clotrimazole
5

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Esophageal candidiasis

Preferred Treatment: ___ 200 mg (up to 400 mg) IV or PO daily for ___ - ___

use ___ agents only

fluconazole
14-21 days
systemic

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Vulvovaginal candidiasis

Uncomplicated disease:
- Fluconazole ___ mg PO x __ dose
- Topical azoles (clotrimazole, butoconazole, miconazole, tioconazole, or terconazole) for 3-7 days
- ___ 300 mg PO BID x 1 day

Severe disease:
- Fluconazole 100-200 mg PO daily or topical antifungals for ≥ __ days

Azole-refractory C. glabrata vaginitis:
___ 600 mg vaginal suppository once daily for 14 days

Recurrent: regimens with ___ , ___ and ___

150, 1
Ibrexafungerp
7
Boric acid
Oteseconazole, Fluconazole, and ibrexafungerp

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Vulvovaginal candidiasis - prophylaxis

T or F: Daily prophylaxis should only be considered for patients with frequent or severe recurrences of esophagitis or vaginitis

TRUE
Routine primary prophylaxis and chronic suppressive therapy to prevent recurrent infection (secondary prophylaxis) is NOT recommended

want to avoid resistance

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Cryptococcal Meningitis

The majority (90%) of infections due to Cryptococcus neoformans are observed among patients with AIDS and CD4 counts < ___ cells/mm3

100

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Cryptococcal Meningitis

If patient is not on ART, the initiation of ART should be ___ until induction (first 2 weeks) and possibly the total
induction/consolidation phases (10-12 weeks) to avoid IRIS

3 phases
1) ___ : 2 weeks
2) ___ : ≥8 weeks
3) ___ : 1 year

inductions
consolidation
maintenance

Cryptococcal Meningitis

Preferred induction: __ weeks followed by consolidation
- ____ 3-4 mg/kg IV once daily + ___ 25 mg/kg PO QID for 2 weeks
- Follow patients in the hospital for at least 7 days and ideally 14 days
- Check daily LPs if ICP elevated

Preferred consolidation: ≥ __ weeks followed by maintenance
- ____ 800 mg PO daily ( ___ mg PO daily in stable patients with sterile CSF
culture and on ART)

Preferred maintenance:
- Fluconazole ___ mg PO daily for 1 ___ or longer

2, Amphotericin B, flucytosine
8, fluconaxole, 400
200, year

Cryptococcal Meningitis

T or F: Prophylaxis is recommended for Cryptococcal Meningitis

FALSE
- Routine primary prophylaxis is NOT recommended
- Secondary prophylaxis is required after induction/consolidation therapy. Continue oral fluconazole for at least one year (maintenance)
- May be discontinued if patient has completed one year, is asymptomatic, and has CD4 count ≥100 cell/mm3 for 3 months on ART with a suppressed viral load
- Restart prophylaxis if the patient’s CD4 count is < 100 cells/mm3

Histoplasmosis

T or F: IRIS has rarely been reported with histoplasmosis, so people with HIV diagnosed with histoplasmosis should start ART as soon as possible after initiating antifungal therapy

TRUE

Histoplasmosis - Mild – Moderate Disease:

___ 200 mg PO TID x 3 days, then 200 mg PO BID for ≥ ___months

Alternatives:
- Posaconazole 300 mg PO BID x 1 day, then 300 mg PO daily
- Voriconazole 400 mg PO BID x 1 day, then 200 mg BID
- Fluconazole 800 mg PO daily

Itraconazole, 12

Histoplasmosis - Severe Disease:

Liposomal ____ 3 mg/kg IV daily for at least 2 weeks followed by ___ 200 mg PO TID x 3 days, then 200 mg PO BID for at least ___ months

Alternatives:
- For use if a patient cannot take itraconazole - Amphotericin B lipid complex 5 mg/kg IV daily for at least 2 weeks followed by posaconazole,
voriconazole, or fluconazole as listed above if; duration at least 12 months

amphotericin B
itraconazole
12

Histoplasmosis - Use of prophylaxis

Primary
- only for people with CD4 count < ___ cells/mm3 and at a high risk because of occupational exposure or living in a community with a hyperendemic rate of histoplasmosis (>10 cases per 100 person-years)
- ___ 200 mg PO daily
- May stop primary prophylaxis in patients taking ART with CD4 count ≥ ___ cells/mm3 for __ months and with viral suppression on ART

150
Itraconazole
150, 6

Histoplasmosis - Use of prophylaxis

Secondary
- Secondary prophylaxis with ___ 200 mg PO daily also recommended for severe disseminated or CNS infection after completing maintenance therapy for ≥ __ months of treatment or relapse despite appropriate initial therapy (after reinduction therapy)

May stop secondary prophylaxis if the following criteria are
met:
- Received azole therapy for > ___ year, and
- Negative fungal blood cultures, and
- Serum or urine Histoplasma antigen below the level of quantification, and
- Viral suppression on ART, and
- CD4 count ≥ ___ cells/mm3 for ≥ ___ months in response to ART

Restart prophylaxis if the patient’s CD4 count is < ___ cells/mm3

itraconazole, 12
1, 150, 6
150

# Infections Due to Mycobacterium avium Complex (MAC) Patients with disseminated MAC who are not on ART Should have ART initiated ___ (preferably with initiation of MAC therapy). Treatment of MAC should include at least ___ drugs as initial therapy to prevent or delay emergence of resistance.

ASAP 2

# Infections Due to Mycobacterium avium Complex (MAC) Preferred Treatment: - ___ 500 mg PO BID + ___ 15 mg/kg PO daily - OR - ____ 500-600 mg PO daily + ___ 15 mg/kg PO daily when intolerance or drug interactions preclude the use of clarithromycin If more severe disease, add ___ 300 mg PO daily. If more severe disease present, the risk of mortality is high, drug ___ is likely, CD4 count is < ___ cells/mm3, high mycobacterial loads in the blood, or in the setting of ineffective ART, a fourth drug should be considered. - ___ 500 mg or moxifloxacin 400 mg QD - ___ 10-15 mg/kg IV daily or streptomycin 1 gm IV or IM daily - ___ , tedizolid, or omadacycline (for refractory MAC cases)

- Clarithromycin, ethambutol - Azithromycin, ethambutol - rifabutin - resistance, 50 - Levofloxacin - Amikacin - Linezolid

# MAC Treatment for disseminated MAC should be administered for ≥ ___ months - Shorter duration may be considered depending on the degree of immunologic recovery following initiation of ART. CD4 count should be > ___ cells/mm3 for ≥ ___ months before discontinuation of therapy

- 12 - 100 - 6

# MAC - Use of Prophylaxis T or F: recommended for those who immediately initiate ART after HIV diagnosis

FALSE: NOT recommended

# MAC - Use of Prophylaxis Primary: - CD4 count < ___ cells/mm3 AND not receiving ART or remains viremic on ART or has no options for a fully suppressive ART regimen - Disseminated MAC disease should be ruled out before starting primary prophylaxis - Preferred regimen: ___ 1,200 mg PO once weekly - Discontinue primary prophylaxis if the patient is continuing on a fully suppressive ART regimen - Restart primary prophylaxis if CD4 count falls < ___cells/mm3 and patient NOT on fully suppressive ART | I know we said prophylaxis not recommended but this is if ART flops

- 50 - Azithromycin

# MAC - Use of Prophylaxis Secondary: - Treatment duration should be at least ___ months - Shorter duration may be considered, but CD4 count should be > ___ cells/mm3 for ≥ __ months in response to ART ___ 500 mg PO BID with ___ 15 mg/kg PO daily ± ___ 300 mg PO daily Can stop secondary prophylaxis if the following criteria are fulfilled: - Completed ≥ __ months of therapy, and - No signs and symptoms of MAC disease, and - Have sustained (> __ months) CD4 count > ___ cells/mm3 in response to ART - Restart secondary prophylaxis if CD4 count < ___ cells/mm3 and a fully suppressive ART regimen is not possible | I know we said prophylaxis not recommended but this is if ART flops

- 12 - 100, 6 - Clarithromycin, Ethambutol - 12 - 6, 100 - 100

# Pneumocystis jirovecii Pneumonia (PJP) Treatment: - In the immunocompromised host, untreated PJP is almost uniformly fatal. - After initiation of treatment for PJP, patients with AIDS tend to get sicker before they improve, and they may take a longer time to display a clinical response. - People with HIV who develop PJP despite TMP-SMZ prophylaxis usually can be treated effectively with standard dose TMP-SMZ - If not already started , ART Should be initiated in patients within ___ weeks of diagnosis of PJP, if possible.

- 2

# Pneumocystis jirovecii Pneumonia (PJP) MODERATE-SEVERE DISEASE Preferred Treatment: - Trimethoprim-sulfamethoxazole ___ - ___ mg/kg/day of the TMP component IV divided q6-8h for ___ days (may switch to PO after clinical improvement Alternative Therapy: - ___* 30 mg PO once daily plus ___ (600 mg IV q6h, 900 mg IV q8h, 450 mg PO q6h, or 600 mg PO q8h), or - Pentamidine 4 mg/kg IV once daily infused over >60 minutes (may decrease to 3 mg/kg if SE occur) (less effective and more SE vs. primaquine + clindamycin) Adjunctive Corticosteroids: - Use for moderate to severe PJP (pO2 < ___ mmHg on room air) - Start ideally within ___ hrs of initiating PJP therapy - ___ 40 mg PO BID x 5 days, then 40 mg PO daily x 5 days, then 20 mg daily x 11 days - IV methylprednisolone can be given ___ % of prednisone dose, if needed

- 15-20 mg/kg/day - 21 days - Primaquine, clindamycin - 70 - 72 - prednisone - 80%

# Pneumocystis jirovecii Pneumonia (PJP) MILD-MODERATE DISEASE Preferred Treatment: - Trimethoprim-sulfamethoxazole ___ - ___ mg/kg/day PO given in three divided doses, OR - TMP-SMZ, ___ DS tablets PO ___ Alternative Therapy: - ___* 100 mg PO daily + ___ 15 mg/kg/day PO given in three divided doses, or - ___ * 30 mg PO once daily plus ___ (450 mg PO q6h or 600 mg PO q8h), or - ___ 750 mg PO BID ___ levels should be checked before administration of dapsone or primaquine

- 15-20 - 2, TID - dapsone, TMP - primaquine, clindamycin - atovaquone - G6PD

# PJP Use of Prophylaxis Primary prophylaxis should be given to prevent the first episode of PJP in all HIV-infected patients with: - CD4 cell count ___ - ___ cells/mm3, if HIV RNA level ___ detection limits - CD4 cell count < ___ cells/mm3, regardless of HIV RNA level Secondary prophylaxis must be given after completion of treatment for an acute episode of PJP in **ALL** patients - Can discontinue prophylaxis when CD4 count increases to ≥ ___ cells/mm3 for > ___ months in response to ART - Can consider when CD4 count is 100-200 cells/mm3 if HIV RNA remains ___ limits of detection for ≥ 3-6 months - Restarting prophylaxis: CD4 count < ___ cells/mm3 regardless of HIV RNA level

- 100-200, above - 100 - 200, 3 - below - 100

# Infections Due to Toxoplasma gondii - Clinical disease almost exclusively occurs because of ___ of latent tissue cysts - rare among patients with a CD4 cell count >200 cells/mm3 - Greatest risk of developing clinical disease is among patients with CD4 cell count < 50 cells/mm3

- reactivation

# Infections Due to Toxoplasma gondii Diagnosis: - Seropositive for anti-toxoplasma immunoglobulin (IgG) antibodies - CT scan or MRI of the brain usually reveals one or more ___ ___ lesions in grey matter of the cortex or basal ganglia - If patients do not respond to therapy, consider other causes (lymphomas, TB, etc.)

- ring advancing

# Infections Due to Toxoplasma gondii - In the immunocompromised host, untreated toxoplasmosis is almost uniformly fatal. - Clinical response usually seen within 14 days of treatment. - Therapy for acute infection should be continued for at least ___ weeks. Longer courses may be required. - Adjunctive ___ should be given to patients with mass effect associated with focal lesions or associated edema and discontinued as soon as feasible. - ___ should be administered to patients with a history of seizures at least through the period of acute treatment but should NOT be administered prophylactically in all patients. - If not already started, ART Should be initiated in patients within __ - __ weeks of the diagnosis/treatment of toxoplasmosis.

- 6 weeks - corticosteroids - Anticonvulsants - 2-3 weeks

# Infections Due to Toxoplasma gondii Preferred Regimens for Acute Infection: ___ 200 mg PO x 1 followed by weight- based dosing: Body weight ≤ 60 kg: - pyrimethamine 50 mg PO daily + - sulfadiazine 1,000 mg PO q6h + - leucovorin 10-25 mg PO daily (can increase to 50 mg daily or BID) Body weight > 60 kg: - pyrimethamine 75 mg PO daily + - sulfadiazine 1,500 mg PO q6h + - leucovorin 10-25 mg PO daily (can increase to 50 mg daily or BID) OR ___ 5 mg/kg (TMP) (IV or PO) BID Total duration: at least __ weeks

- Pyrimethamine - Trimethoprim-sulfamethoxazole - 6

# Infections Due to Toxoplasma gondii Preferred Regimens for Chronic Maintenance: - ___ 25-50 mg PO daily + sulfadiazine 2,000-4,000 mg PO daily (in 2-4 divided doses) + leucovorin 10-25 mg PO daily OR ___ DS one tablet PO BID

- Pyrimethamine - TMP-SMZ

# Infections Due to Toxoplasma gondii - Prophylaxis Primary: - Primary prophylaxis should be given to patients who are Toxoplasma IgG positive with CD4 cell count < ___ cells/mm3 - Preferred regimen: ___ DS one tablet PO daily - Can discontinue primary prophylaxis when CD4 cell count is > ___ cells/mm3 for > __ months in response to ART or if CD4 cell count is 100-200 cells/mm3 and HIV RNA below limits of detection for at least __ - __ months - Restart primary prophylaxis if CD4 count falls < ___ cells/mm3 OR if CD4 count is 100-200 cells/mm3 and HIV RNA is ___ detection limits

- 100 - TMP-SMZ - 200, 3 - 3-6 - 100, above

# Infections Due to Toxoplasma gondii - Prophylaxis Secondary: - Secondary prophylaxis should be given to ALL patients after completion of treatment for an acute episode - Can discontinue prophylaxis when CD4 count >___ cells/mm3 for > __ months in response to ART, AND pt. has had successful completion with initial therapy, AND pt. is asymptomatic w/ s/s for TE - Restart secondary prophylaxis if CD4 count < ___ cells/mm3 ___ of HIV RNA level

- 200, 6 - 200, regardless