Opportunistic HIV Illness Flashcards
Stage 3 HIV
- CD4 < 200
- Development of Stage-3-defining OI (will always be stage 3 after this development)
Stage-3-Defining OI
- Opportunistic infection or neoplasm that are common with HIV
- May indicated that person is immunosuppressed and infected with HIV
Stage-3-Defining OI Examples
- Oral candidiasis
- Pneumocystic pneumonia
- Disseminated MAC infection
- Toxoplasmosis
- Cytomegalovirus
- Cryptococcal meningitis
- Cryptosporidiosis
- Coccidioidomyocosis
- Kaposi sarcoma
Prevention Considerations
Prevention based on:
- Prophylaxis
- SE of prophylaxis
- Severity of disease
- Effectiveness of treatment
- Potential for resistance
- Cost
- Primary prevention: based on CD4 count
- Secondary prevention: patients with relapse risks
Primary Prevention OI
- Pneumocystis pneumonia
- Toxoplasma encephalitis
- Disseminated MAC disease
Vaccinations!!!
Secondary Prevention OI
- Pneumocystis pneumonia
- Toxoplasma encephalitis
- Disseminated MAC disease
- Cytomegalovirus
- Cryptococcal Meningitis
- Histoplasmosis
- Coccidioidomycosis
Mucocutaneous Candidiasis
- Oropharyngeal and esophageal candidiasis are common
- Increased risk when CD4 <200 cells
- HAART reduces likelihood of infection
- No measures available to reduce exposure
- Primary prophylaxis not recommended
Oropharyngeal Candidiasis Treatment
Preferred: Fluconazole 100 mg PO daily
Alternatives
- Clotrimazole troches
- Miconazole buccal tables
- Itraconazole solution
- Posaconazole suspension
- Nystatin suspension
Duration: 7-14 days
Esophageal Candidiasis
Preferred
- Fluconazole 100 mg IV/PO daily
- Itraconazole solution 200 mg PO daily
Alternative:
- Voriconazole
- Isavuconazole
- Micafungin
- Liposomal amphotericin B
Duration: 14-21 days
Triazole AE
- Class: GI disturbances, hepatotoxicity, Rash
- Itraconazole: negative inotropic effect
- Voriconazole: visual disturbances and visual/auditory hallucinations
-Many CYP interactions including PIs (fluconazole preferred)
PCP
- Pneumocystis Pneumonia
- Occurs in ~80% of of AIDS patients prior to ART and primary prophylaxis
- Now mainly occurs in those who are unaware of these serostatus or don’t receive HIV care
PCP Risks
-CD4 < 200
OR if CD4 > 200:
- H/O PCP
- Symptomatic HIV infection
- Recurrent bacterial pneumonia
- Rapidly declining CD4 counts
- High plasma HIV RNA
PCP Presentation
- Fever
- Dyspnea
- Nonproductive cough
- Hypoxemia (mild-severe)
- Elevated lactate dehydrogenase (>500)
PCP Diagnosis
- CT: patched ground-glass opacities
- Fluorescent stain: induced sputum, BAL (preferred)
Primary Prevention PCP Criteria
- Recommended: CD4 < 200
- Consider if CD4 < 14% or count is between 200-250 and ART is delayed
PCP Primary Prevention
- Bactrim DS PO Daily*
- Bactrim SS PO Daily*
Alternatives:
- Bactrim DS PO M-W-F*
- Dapsone QD or BID (dose) (+pyrimethamine + leucovorin*)
- Atovaquone 1500 PO with food*
- Aerosolized pentamidine 300 mg q4w
- = toxoplasmosis coverage
Bactrim
- MoA: Folic acid synthesis inhibitors
- AE: N/V, rash, photosensitivity, bone marrow suppression, renal dysfunction, hyperkalemia
- Renal adjustment: not needed with prophylactic doses
- Normally 1/2 dose at CrCl < 30 and D/C if CrCl < 15
- Monitoring: CBC and K+
Sulfonamide Hypersensitivity
- Higher incidence in AIDS patients
- Fever, maculopapular rash, develops 7-14 days after starting
- Skin testing isn’t helpful
Dapsone
- 100 mg QD or 50 mg BID
- MoA: Inhibits folate synthesis
- AE: rash, photosensitivity, anemias, hepatitis
- Monitoring: G6PD before starting, CBC, LFTs
- Needs additional agents for toxoplasmosis coverage
Atovaquone
- 1500 mg PO daily
- Take with food
- MoA: Inhibits nucleic acid synthesis
- Monitoring: LFTs
Aerosolized Pentamidine
- 300 mg q4weeks
- Via respigard II
- MoA: inhibits nucleic acid synthesis
- AE: Nausea, HA, bronchospasm, dyspnea, dizziness, syncope
D/C Prophylaxis Conditions
- CD4 > 200 for > 3 mo
- Can consider when CD4 100-200 if patients on ART and viral load is undetectable for >= 3 mo
D/C Prophylaxis Reasoning
- Prophylaxis has limited disease prevention data
- Reduced pill burden
- Reduces potential drug toxicity
- Reduces cost
PCP Treatment
-Initiated with definite diagnosis
-Bactrim 15-20 mg/kg/day IV or PO q8H x 21 days (based on trimethoprim)
-Switch to PO once stable
-Prednisone is added in severe disease where PaO2 < 70
Prednisone taper: 40 mg BID days 1-5, 40 mg QD days 6-10, 20 mg QD days 11-21
-Start HAART within 2 weeks of diagnosis when possible
Adjunctive Steroids for PCP Treatment
- For moderate to severe disease (PaO2 < 70)
- Give as early as possible, within 72 hours
- Decreases inflammatory response
- Reduces risk of respiratory failure and death
- Methylprednisolone can be used if IV is necessary at 75% of prednisone dose
PCP Alternative Treatments
Moderate - Severe:
- IV Pentamidine
- PO Primaquine + IV/PO Clindamycin
Mild-Moderate:
- PO Atovaquone
- PO Dapsone + TMP
- PO Primaquine + IV/PO Clindamycin
Treatment: 21 days
Pentamidine
- Not received outpatient
- Life threatening AEs: hypoglycemia, hypotension
- Other AEs: cumulative nephrotoxicity, arrhythmias, pancreatitis, bone marrow suppression, tissue necrolysis at injection site
- Monitor: blood pressure, glucose, renal function, electrolytes, CBC
Primaquine
- 300mg PO daily
- AE: N/V, rash, anemia
- Monitor: CBC, G6PD before starting
Clindamycin
- 600 mg PO q8H
- AE: rash, N/V diarrhea, hepatitis
- Monitoring: bowel frequency, LFTs
PCP Preventing Recurrence
- Secondary prophylaxis is same regimen as primary
- Continue prophylaxis after treatment is completed
- D/C prophylaxis once HAART patients CD4 > 200 for 3 months
- Continue for life if PCP occurred when CD4 > 200 while on ART
Toxoplasmosis
- Protozoa found in undercooked meat and spread in cat feces
- Reactivation disease: CD4 < 100 which results in cerebral or disseminated disease
Toxoplasmosis Encephalitis Presentation
- HA
- Confusion
- Motor weakness
- Seizures
- Coma
Toxoplasmosis Diagnosis
- Toxo IgG+ (absence means diagnosis unlikely)
- CT/MRI: multiple lesions with cerebral edema
- Biopsy and stain uncommon
- PSR of CSF has low sensitivity
Preventing Toxo Exposure
- Test for Toxo IgG at baseline
- Avoid raw/undercooked meat
- Wash hands after handling meat, fruit, vegetables, soil
- Cat owners: avoid changing litter box and only feed dried, commercial food
- Retest IgG if CD4 declines < 100
Toxoplasmosis Primary Prevention
- Initiate is CD4 < 100
- Preferred: Bactrim DS PO Daily
Alternatives:
- Bactrim SS PO QD
- Bactrim DS PO M-W-F
- Dapsone + Pyrimethamine + Leucovorin
- Atovaquone
-D/C when CD4 > 200 for 3 months or CD4 between 100-200 and patient’s on ART and viral load undetectable for 3-6 months
Pyrimethamine
- MoA: folate inhibitor
- Penetrates CSF
- AE: Rash, anemia, neutropenia, thrombocytopenia
- Administer leucovorin with all regimens
- Monitor CBC
Toxo Encephalitis Treatment
Preferred for >60 kg: -Pyramethamine 200 mg PO once then 75 mg PO QD PLUS -Sulfadiazine 1.5 g PO q6h PLUS -Leucovorin 25 mg PO QD
- Duration: >= 6 weeks
- Continue maintenance after completion
- Use AEDs if history of seizures
Sulfadiazine
- MoA: folate inhibitor
- AE: rash, N/V, diarrhea, photosensitivity, bone marrow suppression, crystalluria
- Monitor: CBC, UA
- Advise patient to maintain adequate hydration
Toxo Encephalitis Alternative Treatment
- Sub sulfadiazine with Clindamycin or Atovaquone if allergic
- Bactrim 5mg/kg PO/IV BID
- Atovaquone on its own
Toxoplasmosis Secondary Prophylaxis
-50-80% relapse within months
Maintenance Therapy:
-Pyrimethamine + Sulfadiazine + Leucovorin
Alternatives:
- Pyramethine + Clinda
- Bactrim DS
- Atovaquone
-D/C if CD4 > 200 for >= 6mo
MAC Characteristics
- Cell wall as mycolic acid
- Slow-growing
- Transmitted in air or ingestion
- Risk: CD4 < 50
- 3x risk of death
MAC Presentation
- Persistent fever
- Weight loss
- Night sweats
- Diarrhea/abdominal pain
- Anemia
- Lymphadenopathy/hepatosplenomegaly
MAC Primary Prophylaxis Criteria
-Not recommended in patients who immediately start ART
Criteria
-Not on fully suppressive ART
AND
-CD4 < 50
MAC Primary Prophylaxis Regimens
- Azithromycin
- Clarithromycin
D/C with initiation of effective ART
MAC Treatment
-Minimally 2 effective drugs to prevent ressitance
Preferred: -Clarithromycin PLUS -Ethambutol \+/- -Rifabutin
Alternative: Azithromycin for Clarithromycin
3rd/4th Agent in Disseminated MAC
Consider when:
- High mycobacterial load (>2 log CFU)
- Absence of effective ART
- High risk of mortality (CD4 < 50)
-Options: Rifabutin, Fluoroquinolone, injectable aminoglycoside
Clarithromycin/Azithromycin
- GI symptoms: diarrhea, nausea, abdominal pain
- Metallic taste
- LFT elevations
- QTc prolongation
-Monitor: LFTs, DDI
Ethambutol
- MoA: Inhibits cell wall synthesis
- AE: visual disturbances
- Adjust if CrCl < 50
- Monitor: renal function, eye exams at baseline then monthly
Rifabutin
- MoA: inhibits RNA synthesis
- AE: hepatotoxicity, red/orange secretions, rash, GI disturbances, anemia
- Monitor: LFTs, CBC
- Adjust dose with CYP inducers/inhibitors
MAC Treatment
- Optimized ART necessary
- Start ART at same time if possible
- Consider pill burdens, toxicity, IRIS
IRIS
- Immune reconstitution inflammatory syndrome
- Paradoxical reaction with initiation of HAART
- Occurs in low CD4 count patients with rapid increases
MAC Treatment Duration/Secondary Prophylaxis
- Duration >= 12 months
- No signs/symptoms of MAC
- CD4 > 100 for >= 6 mo