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Pneumocystis jiroveci Pneumonia (PCP) |
Acute therapy
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Trimethoprim-sulfamethoxazole (TMP/SMX): [15-20 mg TMP and 75-100 mg SMX]/kg body weight/day IV administered q6h or q8h or
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Same daily dose of TMP/SMX PO in 3 divided doses; or
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TMP-SMX DS 2 Tablets 3 times a day
Total duration—21 days
Chronic maintenance therapy (Secondary prophylaxis) First choice:
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Trimethoprim-sulfamethoxazole (TMP-SMX) 1 double-strength Tablet (DS) PO QD; or
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TMP-SMX 1 single-strength Tablet (SS) PO QD Alternatives:
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Dapsone 50 mg PO twice daily or 100 mg PO daily; or
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Dapsone 50 mg PO daily plus pyrimethamine 50 mg PO weekly plus leucovorin 25 mg PO weekly; or
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Dapsone 200 mg PO plus pyrimethamine 75 mg PO plus leucovorin 25 mg PO weekly; aerosolized pentamidine 300 mg every month via Respingard nebulizer (manufactured by Marquest, Englewood, Colorado); or
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Atovaquone 1500 mg PO QD; or
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TMP-SMX 1 DS PO TIW
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For severe PCP: -
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Pentamidine 4 mg/kg QD infused over at least 60 minutes, some specialists reduce dose to 3 mg/kg IV QD because of toxicities
For mild-to-moderate PCP:
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Dapsone 100 mg PO QD and TMP 15 mg/kg/day PO (3 divided dose); or
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Primaquine 15-30 mg (base) PO QD and clindamycin 600-900 mg IV q6h to q8h or clindamycin 300-450 mg PO q6h to q8h; or
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Atovaquone 750 mg PO BID with food
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Indications for corticosteroids: PaO2 <70 mm/Hg at room air; or alveolar-arterial O2 gradient >35 mm/Hg Prednisone doses (beginning as early as possible and within 72 hours of PCP therapy): 40 mg BID days 1-5, 40 mg QD days 6-10, then 20 mg QD days 11-21 IV methylprednisolone can be administered as 75% of prednisone dose Chronic Maintenance Therapy (Secondary prophylaxis) should be discontinued if CD4+ T lymphocyte count increases in response to ART from <200 to >200 cells/L for ≥3 months |
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Toxoplasma gondii encephalitis (TE) |
Acute therapy
Pyrimethamine 200 mg POx1, then 50 mg (<60 kg body weight) to 75 mg (≥60 kg) PO QD and sulfadiazine 1000 (<60 kg) to 1500 mg (≥60 kg) PO q6h plus leucovorin 10-20 mg PO QD (can increase ≥50 mg) Total duration for acute therapy is at least 6 weeks
Chronic maintenance therapy (Secondary prophylaxis) First choice
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Sulfadiazine 500-1000 mg PO QID plus pyrimethamine 25-50 mg PO QD plus leucovorin 10-25 mg by mouth daily Second choice Clindamycin 300-450 mg PO every 6-8 hours plus
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pyrimethamine 25-50 mg PO QD plus leucovorin 10-25 PO QD; or Atovaquone 750 mg PO every 6-12 hours with or
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without pyrimethamine 25 mg PO QD plus leucovorin 10 mg PO QD
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Pyrimethamine (leucovorin) and clindamycin 600 mg IV or PO q6h; or
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TMP-SMX (5 mg/kg TMP and 25 mg/kg SMX) IV or PO bid; or
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Atovaquone 1,500 mg PO BID with meals (or nutritional supplement) and pyrimethamine (leucovorin); or
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Atovaquone 1500 mg PO BID with meals (or nutritional supplement) and sulfadiazine 1000-1,500 mg PO q6h; or
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Atovaquone 1500 mg PO BID with meals; or
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Pyrimethamine (leucovorin) and azithromycin 900-1200 mg PO QD
For severely iII patients who cannot take oral medications
TMP-SMX IV and pyrimethamine PO For other regimens with limited experience, see text. |
Adjunctive corticosteroids (e.g., dexamethasone) should be administered when clinically indicated for treatment of mass effect attributed to focal lesions or associated edema and discontinued as soon as clinically feasible Anticonvulsants should be administered to patients with a history of seizures
Secondary prophylaxis may be discontinued if
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Free of TE signs and symptoms; and sustained CD4+ T lymphocyte count of >200 cells/L for >8 months of ART
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Mycobacterium tuberculosis (MTB) |
For drug-sensitive MTB
Initial phase (8 weeks)
Isoniazid (INH) 5 mg/kg body weight (max: 300 mg) PO QD and [rifampin 10 mg/kg (max: 600 mg) PO QD or rifabutin 300 mg PO QD] (or dose adjusted based on concomitant meds) and pyrazinamide (PZA) (dose based on weight) PO QD and ethambutol (EMB) (dose based on weight) PO QD
Continuation phase (19 weeks)
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INH 5 mg/kg (max: 300 mg) PO QD and [rifampin 10 mg/kg (max: 600 mg) or rifabutin 300 mg PO QD]; or
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INH 15 mg/kg (max: 900 mg) PO BIW or TIW plus [rifampin 10 mg/kg (max: 600 mg) or rifabutin 300 mg PO TIW]
In patients with delayed clinical or microbiologic response to initial therapy (e.g., sputum culture (+) after 2 months or if cavitary pulmonary lesions are present), total duration up to 9 months |
Treatment for drug-resistant MTB:
Resistant to INH
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Discontinue INH (and streptomycin, if used)
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Rifamycin, PZA, and EMB for 6 months; or rifamycin and EMB for 12 months (preferably with PZA during at least first 2 months
Resistant to rifamycin
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INH and PZA and EMB and a fluoroquinolone (e.g., levofloxacin 500 mg/day) for 2 months, followed by 10-16 additional months with INH and EMB and fluoroquinolone
Multidrug resistant (MOR) TB—both INH and rifamycin resistant
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Therapy should be individualized based on resistance pattern and with close consultation with experienced specialist
TB treatment in patients with liver disease
If AST ≥ 3 times normal before treatment initiation
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Standard therapy with frequent monitoring; or
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Rifamycin and EMB and PZA for 6 months
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INH and rifamycin and EMB for 2 months, then INH and rifamycin for 7 months
For patients with severe liver disease
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Rifamycin and EMB for 12 months (preferably with another agent such as fluoroquinolone for first 2 months)
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Treatment by directly observed therapy is strongly recommended for all HIV patients Rifabutin has less drug interaction potential and can be used in place of rifampin Rifapenthe administered once weekly can result in development of resistance. It is not recommended among HIV patients Twice weekly intermittent regimen containing rifamycin might lead to rifamycin resistance, particularly among advanced HIV patients with CD4+ T-cell count <100 cells/L; in this situation, therapy must be administered as daily or three times weekly For paradoxical reaction that is not severe, may be treated with nonsteroidal anti-inflammatory drugs (NSAIDs) without change in TB or HIV medications |
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| Candidiasis (mucosal) |
Oropharyngeal candidiasis Initial episodes (7-14 day treatment)
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Fluconazole 100 mg PO QD; or
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Itraconazole oral solution 200 mg PO QD; or
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Clotrimazole troches 10 mg PO 5 times daily; or
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Nystatin suspension 4-6 mL QID or 1-2 flavored pastilles 4-5 times daily
Esophageal candidiasis (14-21 days)
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Fluconazole 100 mg (up to 400 mg) PO or IV QD; or
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Itraconazole oral solution 200 mg PO QD
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Voriconazole 200 mg PO BID
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Caspofungin 50 mg IV QD
Vulvovaginitis
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Topical azoles (clotrimazole, butoconazole, miconazole, ticonazole, or terconazole) for 7-10 days
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Topical nystatin 100,000 units/day as vaginal Tablet for 14 days
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Oral itraconzaole 200 mg BID for 1 day or 200 mg QD for 3 days
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Oral fluconazole 150 mg for 1 dose
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Fluconazole-refractory oropharyngeal candidiasis
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Itraconzaole oral solution ≥200 mg PO QD; or
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Amphotericin B suspension 100 mg/mL (not available in U.S.)—1 mL PO QID; or
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Amphotericin B deoxycholate 0.3 mg/kg IV QD
Fluconazole-refractory esophageal candidiasis
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Caspofungin 50 mg IV QD; or
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Voriconazole 200 mg PO or IV BID
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Amphotericin B 0.3-0.7 mg/kg IV QD; or
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Amphotericin liposomal or lipid complex 3-5 mg/kg IV QD
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Suppressive therapy—generally not recommended unless patients have frequent or severe recurrences
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Oropharyngeal candidiasis—fluconazole or itraconazole oral solution may be considered
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Vuivovaginal candidiasis—daily topical azole for recurrent cases
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Esophageal candidiasis—fluconazole 100-200 mg QD. Chronic or prolonged use of azoles might promote development of resistance
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Cryptococcus neoformans meningitis |
Acute infection (induction therapy)
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Amphotercin B deoxycholate 0.7 mg/kg body weight IV QD and/or flucytosine 25 mg/kg PO QID for 2 weeks; or
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Liposomal amphotericin B 4 mg/kg IV QD and/or flucytosine 25 mg/kg PO QID for 2 weeks
Consolidation therapy
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Fluconazole 400 mg PO QD for 8 weeks or until CSF cultures are sterile
Chronic maintenance therapy (Secondary prophylaxis) -
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Fluconazole 200 mg PO QD;
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Induction therapy (alternative)
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Amphotericin B 0.7 mg/kg/day IV for 2 weeks; or
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Fluconazole 400-800 mg/day (PO or IV) for less severe disease
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Fluconazole 400-800 mg/day (PO or IV) and flucytlosine 25 mg/kg PO QID for 4-6 weeks
Consolidation therapy (alternative)
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Itraconazole 200 mg PO BID
Chronic maintenance therapy (alternative)
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Itraconazole 200 mg PO QD—for patients intolerant of or failed fluconazole
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Repeated lumbar puncture might be indicated as adjunctive therapy among patients with increased intracranial pressure Discontinuation of antifungal therapy can be considered among patients who remain asymptomatic, with CD4+ T-lymphocyte count >100-200 cells/L for ≥6 months Some might consider performing a lumbar puncture before discontinuation of maintenance therapy |
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Histoplasma capsulatum infections |
Severe disseminated
Acute phase (3-10 days or until clinically improved)
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Amphotericin B deoxycholate 0.7 mg/kg body weight IV QD; or
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Liposomal amphotericin B 4 mg/kg IV QD
Continuation phase (12 weeks)
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Itraconazole 200 mg capsule PO BID Less severe disseminated
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Itraconazole 200 mg capsule PO TID for 3 days, then 200 mg PO BID for 12 weeks Meningitis
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Amphotericin B deoxycholate or liposomal for 12-16 weeks
Chronic maintenance therapy (secondary prophylaxis)
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Itraconazole capsule 200 mg PO QD
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Severe disseminated
Acute phase (alternative)
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Itraconazole 400 mg IV QD
Continuation phase (alternative)
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Itraconazole oral solution 200 mg PO BID
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Fluconazole 800 mg PO QD Mild disseminated
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Fluconazole 800 mg PO QD
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Acute pulmonary histoplasmosis among HIV-1– infected patients with CD4+ T-lymphocyte count >500 cells/L might require no therapy Insufficient data to recommend discontinuation of chronic maintenance therapy. |
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| Herpes simplex virus (HSV) disease |
Orolabial lesions and initial or recurrent genital HSV
Famciclovir 500 mg PO BID or valacyclovir 1 g PO BID or acyclovir 400 mg PO TID for 7-14 days
Moderate-to-severe mucocutaneous HSV infections
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Initial therapy acyclovir 5 mg/kg body weight IV q8h
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After lesions begin to regress, change to famciclovir 500 mg PO BID or valacyclovir 1 g PO BID or acyclovir 400 mg PO TID; continue therapy until lesions have completely healed
HSV keratitis
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Trifluridine 1% ophthalmic solution, one drop onto the cornea every 2 hours, not to exceed 2 drops per day, for no longer than 21 days
HSV encephalitis
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Acyclovir 10 mg/kg IV q8h for 14-21 days
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Acyclovir-resistant HSV
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Foscarnet 120-200 mg/kg/day IV in 2-3 divided doses until clinical response
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Cidofovir 5 mg/kg IV weekly until clinical response
Alternative for acyclovir-resistant HSV infections
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Topical trifluridine
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Topical cidofovir
Note: Neither of these topical preparations is commercially available; extemporaneous compounding of these topical products can be prepared using trifluridine ophthalmic solution and cidofovir for intravenous administration |
Chronic suppressive therapy with oral acyclovir, famciclovir, or valacyclovir might be indicated among patients with frequent or severe recurrences |
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| Varicella zoster virus (VZV) disease |
Primary VZV infection (chickenpox)
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Acyclovir 10 mg/kg body weight IV q8h for 7-10 days
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Switch to oral therapy (acyclovir 800 mg PO QID or valacyclovir 1 g TID or famciclovir 500 mg TID) after defervescence if no evidence of visceral involvement exists
Local dermatomal herpes zoster
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Famciclovir 500 mg or valacyclovir 1 g PO TID for 7-10 days
Extensive cutaneous lesion or visceral involvement
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Acyclovir 10 mg/kg IV q8h, continue until cutaneous and visceral disease clearly resolved
Progressive outer retinal necrosis (PORN) ? Acyclovir IV 10 mg/kg q8h and foscarnet 80 mg/kg IV q8h |
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Corticosteroids for dermatomal zoster are not recommended |
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| Coccidioidomycosis |
Nonmeningeal infection
Acute phase (diffuse pulmonary or disseminated disease)
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Amphotericin B deoxycholate 0.5-1.0 mg/kg body weight IV QD; continue until clinical improvement, usually 500-1,000 mg total dose
Acute phase (milder disease)
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Fluconazole 400-800 mg PO QD; or
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Itraconazole 200 mg PO BID
Meningeal Infections -
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Fluconazole 400-800 mg IV or PO QD
Chronic maintenance therapy (Secondary prophylaxis) -
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Fluconazole 400 mg PO QD; or
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Itraconazole 200 mg capsule PO BID
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Insufficient data to recommend discontinuation of chronic maintenance therapy |
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| Invasive aspergillosis |
Voriconazole 400 mg IV or PO q12h for 2 days, then 200 mg q12h Duration of therapy based on clinical response |
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Not enough data to recommend chronic suppression or maintenance therapy |
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| Cylomegalovirus (CMV) disease |
CMV retinitis
For immediate sight-threatening lesions
Ganciclovir intraocular implant and valganciclovir 900 mg PO QD
For peripheral lesions
Valganciclovir 900 mg PO BID for 14-21 days, then 900 mg PO QD
Chronic maintenance therapy (Secondary prophylaxis) First choice
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Valganciclovir 900 mg PO QD
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Foscarnet 90-120 mg/kg body weight IV QD
CMV esophagitis or colitis -
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Ganciclovir IV or Foscarnet IV for 21-28 days or until signs and symptoms have resolved; oral valganciclovir may be used if symptoms are not severe enough to interfere with oral absorption
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Maintenance therapy is generally not necessary, but should be considered after relapses
CMV pneumonitis -
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Treatment should be considered in patients with histologic evidence of CMV pneumonitis and who do not respond to treatment of other pathogens
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The role of maintenance therapy is not yet established
CMV neurologic disease -
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Ganciclovir IV and Foscarnet IV continue until symptomatic improvement
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Maintenance therapy should be continued for life
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CMV retinitis -
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Ganciclovir 5 mg/kg IV q12h for 14-21 days, then 5 mg/kg IV QD; or
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Ganciclovir 5 mg/kg IV q12h for 14-21 days, then valganciclovir 900 mg PO QD; or
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Foscarnet 80 mg/kg IV q8h or 90 mg/kg IV q12h for 14-21 days, then 90-120 mg/kg IV q24h; or
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Cidofovir 5 mg/kg IV for 2 weeks, then 5 mg/kg every other week; each dose should be administered with IV saline hydration and oral probenecid; or
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Repeated intravitreal injections with fomivirsen (for relapses only, not as initial therapy)
Chronic maintenance therapy -
▪
Cidofovir 5 mg/kg IV every other week with probenecid 2 g PO 3 hours before the dose followed by 1 g PO 2 hours after the dose, and 1 g PO 8 hours after the dose (total of 4 g); or
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Fomivirsen 1 vial (330 mg) injected into the vitreous, then repeated every 2-4 weeks
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Choice of initial therapy for CMV retinitis should be individualized on the basis of location and severity of the lesion(s), level of immunosuppression, and other factors such as concomitant medications and ability to adhere to treatment Initial therapy among patients with CMV retinitis, esophagitis, colitis, and pneumonitis should include optimization of antiretroviral therapy (ART) Some specialists recommend delaying ART among patients with CMV neurologic disease because of concerns about worsening of condition as a result of immune recovery inflammatory reaction Preemptive treatment of patients with CMV viremia without evidence of organ involvement is generally not recommended Maintenance therapy for CMV retinitis can be safely discontinued among patients with inactive disease and sustained CD4+ T lymphocyte (>100-150 cells/L3 for ≥8 months); consultation with ophthalmologist is advised Patients with CMV retinitis who discontinued maintenance therapy should undergo regular eye examination for early detection of relapse Ganciclovir intraocular implants might need to be replaced every 6-8 months for patients who remain immunosuppressed with CD4+ T lymphocyte counts <100-150 cells/μL Immune recovery uveitis (IRU) might develop in the setting of immune reconstitution; treatment of IRU; periocular corticosteroids or short courses of systemic steroid. Because of its poor oral bioavailability and with the availability of valganciclovir, oral ganciclovir should not be used |
