218.1 🎓 醫孞生版

218.1.0.1 📌 䞀頁重點

218.1.0.1.1 CD4 Stratification — OI Risk
CD4 (cells/µL) Common OIs
> 500 TB, candida thrush, herpes zoster (Shingrix recommended), bacterial infections
200-500 Same + TB more severe, varicella, HSV recurrence
100-200 + PJP (Pneumocystis jirovecii pneumonia), CMV, others
50-100 + Toxoplasma encephalitis, cryptococcal meningitis, disseminated MAC, PML
< 50 + CMV retinitis, MAC bacteremia, EBV CNS lymphoma, KS
218.1.0.1.2 Top OIs
218.1.0.1.2.1 Pneumocystis jirovecii Pneumonia (PJP)
  • CD4 < 200
  • Insidious onset (weeks): dry cough, dyspnea, fever, hypoxia
  • CXR: bilateral perihilar interstitial; can be normal early
  • Diagnosis: induced sputum + immunofluorescence; BAL gold standard; β-D-glucan elevated
  • Treatment: TMP-SMX 15-20 mg/kg/day × 21 days; alternatives clindamycin+primaquine, pentamidine, atovaquone
  • Steroid if A-a gradient > 35 or PaO2 < 70 on room air
218.1.0.1.2.2 Toxoplasma Encephalitis
  • CD4 < 100, IgG+
  • Headache, fever, focal neuro signs, seizures
  • MRI: multi-ring enhancing lesions
  • Empirical: sulfadiazine + pyrimethamine + leucovorin × 6 wk; alternative TMP-SMX
  • Don’t biopsy unless atypical / non-responsive
  • 1° prophylaxis: TMP-SMX if CD4 < 100 + Toxo IgG+
218.1.0.1.2.3 Cryptococcal Meningitis
  • CD4 < 100
  • Subacute headache, fever, altered mental status, photophobia
  • LP: high opening pressure, lymphocytic, low glucose
  • Cryptococcal antigen (CrAg) = serum (sensitivity 99%) + CSF
  • Treatment: amphotericin B (liposomal) + flucytosine induction × 14d (AmBisome 4 mg/kg/d + flucytosine 100 mg/kg/d), then fluconazole 800 mg/d × 8 wk → 200 mg/d maintenance
  • Repeated LPs for high pressure (mortality reduction)
  • 1° prophylaxis: serum CrAg screening when CD4 < 100; fluconazole if positive
218.1.0.1.2.4 Disseminated MAC (Mycobacterium avium Complex)
  • CD4 < 50
  • Fever, night sweats, weight loss, anemia, splenomegaly, LAP
  • Treatment: clarithromycin (or azithromycin) + ethambutol + rifabutin (or rifampin if not on PI)
  • ART concurrent (consider IRIS risk)
  • 1° prophylaxis: not routine if ART starting (was azithromycin 1.2 g/wk historically)
218.1.0.1.2.5 CMV Retinitis
  • CD4 < 50
  • Floaters, blurry vision, visual field defects
  • “Pizza pie” fundus
  • Ophthalmology emergent
  • Valganciclovir 900 mg PO bid × 21d induction → 900 qd maintenance + ART (Ch 200)
218.1.0.1.2.6 Other Notable OIs
  • PML (JC virus): CD4 < 100; multifocal white matter demyelination (Ch 210)
  • Primary CNS lymphoma (EBV-driven): ring-enhancing, often single, contrast-enhancing (vs Toxo multi-ring)
  • Disseminated histoplasmosis (Ohio Valley): pancytopenia, fever, LAP; itraconazole + amphotericin
  • Disseminated coccidioidomycosis (SW USA): fungemia; amphotericin → fluconazole
  • Cryptosporidium / Microsporidia / Cyclospora: chronic diarrhea
  • Salmonella bacteremia: recurrent
  • Bacillary angiomatosis (Bartonella): vascular skin lesions
  • Severe Mpox: 2022-2024 outbreaks; CD4 < 200 severe
218.1.0.1.3 Prophylaxis Summary
CD4 Prophylaxis
< 200 + ART starting TMP-SMX for PJP (1 DS qd; or 1 SS qd)
< 100 + Toxo IgG+ TMP-SMX (covers Toxo too)
< 100 + CrAg+ Fluconazole (Cryptococcus secondary)
< 50 + on ART without immune recovery MAC prophylaxis historic (azithromycin); routinely deferred when ART starting
218.1.0.1.4 Discontinue Prophylaxis
  • After CD4 > 200 for 3-6 months on ART (PJP)
  • After CD4 > 100 for 3 months (Toxo)
  • Cryptococcal: complete maintenance + immune recovery
  • Continuous surveillance + vaccines

218.1.0.2 1⃣ Pneumocystis Jirovecii Pneumonia (PJP)

218.1.0.2.1 Microbiology
  • Pneumocystis jirovecii (formerly P. carinii) — fungus
  • Cyst + trophozoite forms
  • Tropism for alveolar epithelium
218.1.0.2.2 Risk
  • HIV CD4 < 200
  • Other immunocompromise: transplant, anti-CD20, high-dose steroid
218.1.0.2.3 Clinical
  • Insidious onset (weeks)
  • Dry cough
  • Progressive dyspnea
  • Low-grade fever
  • Hypoxia (exercise desaturation early; rest later)
  • Lab: ↑ LDH, ↑ β-D-glucan, normal WBC
218.1.0.2.4 Imaging
  • CXR: bilateral perihilar interstitial / “ground-glass”
  • Can be normal early
  • Severe: diffuse + pneumothorax (esp. with pneumocystis cysts)
  • HRCT: ground-glass + cystic changes
218.1.0.2.5 Diagnosis
  • Induced sputum + immunofluorescence (sens 70-80%)
  • BAL + immunofluorescence (gold standard, sens > 95%)
  • Lung biopsy rare
  • PCR (BAL or sputum) — emerging
  • β-D-glucan > 200 pg/mL supportive
218.1.0.2.6 Treatment
218.1.0.2.6.1 First-Line
  • TMP-SMX 15-20 mg/kg/day (TMP component) IV/PO × 21 days
  • Divided q6h (4-5 daily doses)
218.1.0.2.6.2 Alternatives
  • Clindamycin + Primaquine (avoid in G6PD deficiency)
  • Pentamidine IV (toxic — nephro + hypoglycemia + arrhythmia)
  • Atovaquone PO (mild-moderate only)
  • TMP + dapsone (atypical, G6PD screen)
218.1.0.2.6.3 Steroid Adjunct (Adjunctive)
  • A-a gradient > 35 mmHg or PaO2 < 70 mmHg on RA
  • Prednisone 40 mg PO bid × 5d → 40 qd × 5d → 20 qd × 11d (taper)
  • Reduces mortality + need for vent
218.1.0.2.6.4 Treatment Course
  • 21 days for severe
  • 14-21 days for mild-moderate
  • ART started within 2 weeks of OI treatment (current guidelines)
218.1.0.2.7 Prophylaxis
  • Primary: CD4 < 200 → TMP-SMX 1 DS qd (or alternatives)
  • Secondary: continue until CD4 > 200 for 3-6 months on ART
218.1.0.2.8 Alternatives for TMP-SMX Intolerance
  • Dapsone 100 mg qd (G6PD screen)
  • Atovaquone 1500 mg qd with food
  • Pentamidine inhaled 300 mg q month

218.1.0.3 2⃣ Toxoplasma Encephalitis

218.1.0.3.1 Microbiology
  • Toxoplasma gondii — protozoan
  • Cat definitive host
  • Tissue cyst latency in muscle + brain
218.1.0.3.2 Risk
  • HIV CD4 < 100 + IgG positive (latent reactivation)
  • Solid organ transplant + post-transplant reactivation
  • Anti-CD20 / chemo
218.1.0.3.3 Clinical
  • Subacute (days-weeks)
  • Headache, fever, focal neurological signs, seizures
  • Altered mental status
  • Hemiparesis, ataxia, aphasia, etc.
218.1.0.3.4 Imaging
  • MRI multi-ring enhancing lesions in basal ganglia, gray-white junction, with edema
  • Differential: primary CNS lymphoma, brain abscess, PML
218.1.0.3.5 Diagnosis
  • MRI + Toxoplasma IgG+
  • CSF (if LP feasible): Toxo PCR sens 30-50%, Toxo Ag
  • Empirical treatment common (response to therapy = diagnostic)
  • Brain biopsy if no response in 1-2 wk (consider PCNSL)
218.1.0.3.6 Treatment
218.1.0.3.6.1 First-Line
  • Sulfadiazine + Pyrimethamine + Leucovorin × 6 weeks
    • Sulfadiazine 1-1.5 g PO q6h
    • Pyrimethamine 200 mg PO × 1 → 50-75 mg PO qd
    • Leucovorin 10-25 mg PO qd (prevent pyrimethamine marrow toxicity)
218.1.0.3.6.2 Alternative
  • TMP-SMX 5 mg/kg q6-12h × 6 weeks (equivalent efficacy, better tolerated)
  • Pyrimethamine + Clindamycin + Leucovorin
  • Atovaquone + Pyrimethamine + Leucovorin
218.1.0.3.6.3 Steroid
  • For mass effect / edema
  • Dexamethasone 4-6 mg q6h, taper
218.1.0.3.6.4 Treatment Duration
  • 6 weeks
  • Maintenance after acute treatment until immune recovery
218.1.0.3.7 Prophylaxis
  • Primary: CD4 < 100 + Toxo IgG+ → TMP-SMX 1 DS qd
  • Secondary: continue until CD4 > 100 for 3 months on ART
218.1.0.3.8 Immune Reconstitution
  • IRIS possible — paradoxical worsening
  • Continue treatment + steroid for severe

218.1.0.4 3⃣ Cryptococcal Meningitis

218.1.0.4.1 Microbiology
  • Cryptococcus neoformans (worldwide) + C. gattii (warmer + sub-Saharan Africa, Pacific NW USA)
  • Yeast with polysaccharide capsule
  • Inhaled spores → lung → disseminate to CNS
218.1.0.4.2 Risk
  • HIV CD4 < 100
  • Transplant
  • Other immunocompromise
218.1.0.4.3 Clinical
  • Subacute (weeks)
  • Headache, fever, altered mental status, photophobia
  • Focal neuro signs less common (vs Toxo)
  • Increased intracranial pressure (papilledema, cranial nerve palsies)
218.1.0.4.4 Diagnosis
218.1.0.4.4.1 Serum Cryptococcal Antigen (CrAg)
  • Latex agglutination or lateral flow immunoassay
  • Sensitivity 99%, specificity high
  • Should be done in CD4 < 100 routinely
  • Positive → LP + treatment
218.1.0.4.4.2 LP Findings
  • High opening pressure (often > 25 cm H2O)
  • Mildly elevated protein
  • Decreased glucose
  • Lymphocytic pleocytosis (sometimes low cells in AIDS)
  • CSF CrAg positive
  • India ink staining (50% sensitivity)
218.1.0.4.5 Treatment
218.1.0.4.5.1 Induction Phase × 14 days
  • Amphotericin B liposomal (AmBisome) 4 mg/kg/d IV + Flucytosine 100 mg/kg/d PO
  • WHO + IDSA 2024 update
  • Single-dose liposomal amphotericin alternative (HIV resource-limited; non-inferiority)
218.1.0.4.5.2 Consolidation Phase × 8 weeks
  • Fluconazole 800 mg PO qd × 8 weeks
218.1.0.4.5.3 Maintenance Phase
  • Fluconazole 200 mg PO qd
  • Continue until CD4 > 100 for 3 months on ART
218.1.0.4.5.4 LP Management
  • Repeated LPs daily until opening pressure < 25 cm H2O (high pressure → mortality)
  • Lumbar drain for refractory
  • VP shunt if persistent
218.1.0.4.5.5 When to Start ART
  • Delay 4-6 weeks post-cryptococcal meningitis treatment initiation
  • Reduces IRIS risk
  • COAT trial 2014 showed delayed ART superior to immediate
218.1.0.4.6 Prophylaxis
  • Pre-emptive: serum CrAg screening when CD4 < 100; if positive + asymptomatic → fluconazole 400-800 mg qd until immune recovery
  • Primary prophylaxis (asymptomatic, CrAg-) not routine

218.1.0.5 4⃣ Disseminated MAC (Mycobacterium avium Complex)

218.1.0.5.1 Microbiology
  • M. avium + M. intracellulare
  • Slow-growing NTM
  • Environmental (water, soil)
  • Reservoir not human
218.1.0.5.2 Risk
  • HIV CD4 < 50
218.1.0.5.3 Clinical
  • Fever, night sweats, weight loss
  • Anemia, thrombocytopenia
  • Splenomegaly, hepatomegaly
  • Lymphadenopathy
  • Abdominal pain
  • Diarrhea
  • Mycobacteremia (positive blood cultures via MGIT)
  • Bone marrow involvement
218.1.0.5.4 Diagnosis
  • Blood cultures (mycobacterial bottles) — sensitive
  • BM biopsy + culture for fastidious
  • Tissue biopsy: AFB +, granulomas with foamy macrophages
218.1.0.5.5 Treatment
  • Clarithromycin 500 mg PO bid + Ethambutol 15 mg/kg/d + Rifabutin 300 mg/d (if not on PI; or rifampin)
  • Alternative: azithromycin instead of clarithromycin
  • Treat for ≥ 12 months + immune recovery (CD4 > 100 for 6 months)
  • AST may guide
218.1.0.5.6 Prophylaxis
  • Primary: NOT routinely recommended now (with ART starting); historically azithromycin 1.2 g/wk for CD4 < 50
  • Secondary: continue treatment until immune recovery
218.1.0.5.7 IRIS
  • 20-30% develop IRIS after starting ART
  • Paradoxical LAP, fever
  • Continue treatment + steroid for severe

218.1.0.6 5⃣ CMV Retinitis

218.1.0.6.1 Risk
  • HIV CD4 < 50
218.1.0.6.2 Clinical
  • Floaters, blurred vision, visual field defects
  • “Pizza pie” fundus: white retinitis + hemorrhage
  • Often progressive
  • Risk of retinal detachment
218.1.0.6.3 Diagnosis
  • Emergent ophthalmology consult + dilated fundoscopy
  • Pathognomonic appearance
  • CMV PCR of vitreous if uncertain
218.1.0.6.4 Treatment
  • Valganciclovir 900 mg PO bid × 21 days induction
  • Then maintenance: valganciclovir 900 mg PO qd until CD4 > 100 for 3-6 mo on ART
  • Intravitreal ganciclovir for sight-threatening
  • ART concurrent
  • Ophthalmology q3 mo
218.1.0.6.5 Other CMV Disease in HIV
  • Colitis (Ch 200)
  • Esophagitis
  • Encephalitis (rare, severe)
  • Pneumonia (rare)

218.1.0.7 6⃣ Other Notable OIs

218.1.0.7.1 Progressive Multifocal Leukoencephalopathy (PML)
  • JC virus reactivation
  • CD4 < 100 (especially < 50)
  • Subacute neurologic decline (visual, motor, cognitive)
  • MRI: multifocal demyelinating white matter lesions, no enhancement
  • CSF JC PCR
  • Treatment: ART (immune reconstitution = primary intervention)
  • Pembrolizumab emerging adjunct
  • 50%+ survival in modern HIV-PML era
218.1.0.7.2 Primary CNS Lymphoma (PCNSL)
  • EBV-driven in HIV
  • CD4 < 50
  • Single or multifocal contrast-enhancing brain lesions
  • Differential from Toxoplasmosis crucial:
    • Toxo: multi-ring enhancing
    • PCNSL: single (often), homogeneous enhancing
  • Diagnosis: CSF cytology + EBV PCR positive; thallium SPECT (PCNSL high uptake vs Toxo)
  • Treatment: ART + high-dose methotrexate or whole-brain radiation
  • Outcomes improved in ART era
218.1.0.7.3 Disseminated Histoplasmosis
  • Endemic Ohio + Mississippi Valley, Central America, parts of Asia
  • CD4 < 100
  • Fever, weight loss, hepatosplenomegaly, pancytopenia, oral ulcers, skin nodules
  • Treatment: Liposomal amphotericin B × 2 wk → Itraconazole PO × 1 yr
  • Long maintenance until CD4 > 150 for 6 mo
218.1.0.7.4 Disseminated Coccidioidomycosis
  • SW USA endemic
  • CD4 < 100
  • Fever, weight loss, pneumonia, skin lesions, meningitis
  • Fluconazole 400-800 mg/d PO (or itraconazole)
  • Maintenance lifelong if CD4 < 250
218.1.0.7.5 Cryptosporidium + Microsporidia + Cyclospora
  • Chronic diarrhea + weight loss
  • CD4 < 100
  • Stool ova + parasite (modified acid-fast for Cryptosporidium)
  • Treatment:
    • Cryptosporidium: nitazoxanide + ART (immune reconstitution = primary)
    • Microsporidia: albendazole (Encephalitozoon); fumagillin (Enterocytozoon)
    • Cyclospora: TMP-SMX
218.1.0.7.6 Salmonella Bacteremia
  • Recurrent in HIV
  • Especially HIV + CD4 < 200
  • Treatment: ceftriaxone or fluoroquinolone for 2 weeks
  • Long-term suppression considered
218.1.0.7.7 Bacillary Angiomatosis
  • Bartonella henselae or quintana (Ch 164)
  • Cat scratch or louse
  • Vascular skin lesions (mimic KS or pyogenic granuloma)
  • Treatment: erythromycin or doxycycline × 3 months
218.1.0.7.8 Severe Mpox in HIV
  • 2022-2024 outbreak: severe in HIV + CD4 < 200
  • 5-15% mortality in this group
  • Tecovirimat (compassionate use) + supportive
  • ART critical
218.1.0.7.9 Kaposi’s Sarcoma (KS)
  • HHV-8 (KSHV; Ch 201)
  • Cutaneous + mucosal + visceral (lung, GI)
  • Multifocal
  • Treatment: ART + chemotherapy (PEGylated liposomal doxorubicin, paclitaxel)
  • Immune checkpoint inhibitor in some refractory
218.1.0.7.10 Talaromycosis (Penicillium marneffei → Talaromyces marneffei)
  • Endemic SE Asia (Vietnam, Thailand, S China)
  • CD4 < 100
  • Fever, weight loss, hepatosplenomegaly, umbilicated skin lesions
  • Treatment: amphotericin B → itraconazole