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Toxoplasmosis

• Toxoplasma gondii (treatment)

• 1. Lymphadenopathic toxoplasmosis

• Preferred regimen: Treatment of immunocompetent adults with lymphadenopathic toxoplasmosis is rarely indicated; this form of the disease is usually self-limited.

• 2. Ocular disease

• 2.1 Adults

• Preferred regimen: Pyrimethamine 100 mg PO for 1 day as a loading dose, then 25 to 50 mg/day AND Sulfadiazine 1 g PO qid AND folinic acid (Leucovorin 5-25 mg PO with each dose of Pyrimethamine

• 2.2 Pediatric

• Preferred regimen: Pyrimethamine 2 mg/kg PO first day then 1 mg/kg each day AND Sulfadiazine 50 mg/kg PO bid AND folinic acid (Leucovorin 7.5 mg/day PO ) for 4 to 6 weeks followed by reevaluation of the patient's condition
• Alternative regimen: The fixed combination of Trimethoprim with Sulfamethoxazole has been used as an alternative.
• Note: If the patient has a hypersensitivity reaction to sulfa drugs, Pyrimethamine AND Clindamycin can be used instead.

• 3. Maternal and fetal infection

• 3.1 First and early second trimesters

• Preferred regimen: Spiramycin is recommended

• 3.2 Late second and third trimesters

• Preferred regimen: Pyrimethamine/Sulfadiazine AND Leucovorin for women with acute T. gondii infection diagnosed at a reference laboratory during gestation.

• 3.3 Infant

• Note: If the infant is likely to be infected, then treatment with drugs such as Pyrimethamine, Atovaquone, Sulfadiazine, Leucovorin is typical. Congenitally infected newborns are generally treated with pyrimethamine, a sulfonamide, and leucovorin for 1 year.

• 4. Toxoplasma gondii Encephalitis in AIDS

• 4.1 Treatment for acute infection

• 4.1.1 Patients with weight <60 kg
• Preferred regimen: Pyrimethamine 200 mg PO 1 time, followed by Pyrimethamine 50 mg PO qd AND Atovaquone AND Sulfadiazine 1000 mg PO q6h AND Leucovorin 10–25 mg PO qd,
• 4.1.2 Patients with weight ≥60 kg

• Preferred regimen: Pyrimethamine 200 mg PO 1 time, followed by Pyrimethamine 75 mg PO qd AND Sulfadiazine 1500 mg PO q6h AND Leucovorin 10–25 mg PO qd and Leucovorin dose can be increased to 50 mg qd or bid
• Alternative regimen (1): Pyrimethamine AND Leucovorin AND Clindamycin 600 mg IV/ PO q6h
• Alternative regimen (2): TMP-SMX (TMP 5 mg/kg and SMX 25 mg/kg ) IV/PO bid
• Alternative regimen (3): Atovaquone 1500 mg PO bid AND Pyrimethamine AND Leucovorin
• Alternative regimen (4): Atovaquone1500 mg PO bid AND sulfadiazine 1000–1500 mg PO q6h (weight-based dosing, as in preferred therapy)
• Alternative regimen (5): Atovaquone 1500 mg PO bid
• Alternative regimen (6): Pyrimethamine AND Leucovorin AND Azithromycin 900–1200 mg PO qd
• Note: Treatment for at least 6 weeks; longer duration if clinical or radiologic disease is extensive or response is incomplete at 6 weeks.

• 4.2 Chronic maintenance therapy

• Preferred regimen: Pyrimethamine 25–50 mg PO qd AND sulfadiazine 2000–4000 mg PO qd (in 2–4 divided doses) AND Leucovorin 10–25 mg PO qd
• Alternative regimen (1): Clindamycin 600 mg PO q8h AND (Pyrimethamine 25–50 mg AND Leucovorin 10–25 mg) PO qd
• Alternative regimen (2): TMP-SMX DS 1 tablet bid
• Alternative regimen (3): Atovaquone 750–1500 mg PO bid AND (Pyrimethamine 25 mg AND Leucovorin 10 mg) PO qd
• Alternative regimen (4): Atovaquone 750–1500 mg PO bid
• Alternative regimen (5): Sulfadiazine 2000–4000 mg PO bid/qid
• Alternative regimen (6): Atovaquone 750–1500 mg PO bid Pyrimethamine and Leucovorin doses are the same as for preferred therapy
• Note: Adjunctive corticosteroids (e.g., Dexamethasone) should only be administered when clinically indicated to treat mass effect associated with focal lesions or associated edema; discontinue as soon as clinically feasible. Anticonvulsants should be administered to patients with a history of seizures and continued through acute treatment, but should not be used as seizure prophylaxis . If Clindamycin is used in place of Sulfadiazine, additional therapy must be added to prevent PCP.

• Toxoplasma gondii (prophylaxis)

• 1. Prophylaxis to prevent first episode of encephalitis in AIDS

• 1.1 Indications

• Toxoplasma IgG-positive patients with CD4 count <100 cells/µL
• Seronegative patients receiving PCP prophylaxis not active against toxoplasmosis should have toxoplasma serology retested if CD4 count decline to <100 cells/µL. Prophylaxis should be initiated if seroconversion occurred.

• 1.2 Prophylactic therapy

• Preferred regimen: TMP-SMX 1 DS PO daily
• Alternative regimen (1): TMP-SMX 1 DS PO three times weekly
• Alternative regimen (2): TMP-SMX 1 SS PO qd
• Alternative regimen (3): Dapsone 50 mg PO qd AND (Pyrimethamine 50 mg PO AND Leucovorin 25 mg) PO weekly
• Alternative regimen (4): Dapsone 200 mg PO AND Pyrimethamine 75 mg PO AND Leucovorin 25 mg PO weekly
• Alternative regimen (5): Atovaquone 1500 mg PO qd
• Alternative regimen (6): Atovaquone 1500 mg PO AND Pyrimethamine 25 mg PO AND Leucovorin 10 mg PO qd

Varicella zoster

• 1. Varicella zoster treatment

• 1.1 Non Immunocompromised person

• Preferred regimen (1): Acyclovir 500 mg PO five times a dayfor 7-10 days
• Preferred regimen (2): Famciclovir 500 mg PO tid for 7 days
• Preferred regimen (3): Valacyclovir 1 g PO tid for 7 days
• Preferred regimen (4): Brivudin 125 mg PO qd for 7 days

• 1.2 Immunocompromised person requiring hospitalization or persons with sever neurologic complications

• Preferred regimen (1): Acyclovir 10 mg/ kg IV q8h for 7-10 days
• Preferred regimen (2): Foscarnet 40 mg/ kg IV q8h until lesions are healed
• Note: Brivudin is not available in USA and has not been approved by FDA. Foscarnet is not approve by FDA

• 2. Treatment of VZV complications

• 2.1 VZV ophthalmicus

• Treatment includes the following

• (1) Famciclovir OR Valacyclovir for 7–10 days, preferably started within 72 h of rash onset (with Acyclovir IV given as needed for retinitis), to resolve acute disease and inhibit late inflammatory recurrences, AND Prednisone 20 mg PO tid for 4 days or bid for 6 days, and then qd for 4 day
• (2) Bacitracin-Polymyxin ophthalmic ointment administered bid ,to protect the ocular surface;
• (3) Topical Prednisolone 0.125%–1% 2–6 times daily prescribed and managed only by an ophthalmologist for corneal immune disease, episcleritis, scleritis, or iritis;
• (4) Homatropine 5% bid as needed for iritis
• (5) Latanaprost qd and/or Timolol maleate ophthalmic gel forming solution every morning)ocular pressure–lowering drugs given as needed for glaucoma
• Note (1): Systemic steroids are indicated in the presence of moderate to severe pain or rash, particularly if there is significant edema, which may cause orbital apex syndrome through pressure on the nerves entering the orbit.
• Note (2): pain medications and cool to tepid wet compresses (if tolerated) and no topical antivirals, because they are ineffective

• 2.2 VZV retinitis

• Preferred regimen: Acyclovir IV 10–15 mg/kg q8h for 10–14 days followed by Valacyclovir PO 1 g tid daily for 4–6 weeks

• 3 Recommendations for treating varicella zoster virus (VZV) Infections in HIV-Infected adults and adolescents

• 3.1 Primary Varicella Infection (Chickenpox)

• 3.1.1 Uncomplicated Cases

• Preferred regimen (1):Valacyclovir 1 g PO tid for 5–7 days
• Preferred regimen (2): Famciclovir 500 mg PO tid for 5–7 days
• Alternative regimen: Acyclovir 800 mg PO 5 times daily for 5–7 days

• 3.1.2 Severe or Complicated Cases

• Preferred regimen: Acyclovir 10–15 mg/kg IV q8h for 7–10 days
• Note: May switch to oral Famciclovir, Valacyclovir, or Acyclovir after defervescence if no evidence of visceral involvement is evident

• 3.2 Herpes Zoster (Shingles)

• 3.2.1 Acute Localized Dermatomal

• Preferred regimen (1): Valacyclovir 1000 mg PO tid for 7–10 days
• Preferred regimen (2): Famciclovir 500 mg PO tid for 7–10 days
• Alternative Therapy: Acyclovir 800 mg PO 5 times daily for 7–10 days
• Note: Longer duration should be considered if lesions resolve slowly

• 3.2.2 Extensive Cutaneous Lesion or Visceral Involvement

• Preferred regimen: Acyclovir 10–15 mg/kg IV q8h until clinical improvement is evident, then switch to (Valacyclovir 1 g PO tid, Famciclovir 500 mg PO tid, or Acyclovir 800 mg PO 5 times daily)—to complete a 10–14 day course, when formation of new lesions has ceased and signs and symptoms of visceral VZV infection are improving

• 3.3 PORN (Progressive outer retinal necrosis)

• Preferred regimen: Ganciclovir 5 mg/kg and/or Foscarnet 90 mg/kg IV q12h AND Ganciclovir 2 mg/0.05mL and/or foscarnet 1.2 mg/0.05mL intravitreal twice weekly.
• Note: Duration of therapy is not well defined and should be determined based on clinical, virologic, and immunologic response in consultation with experienced ophthalmologist and optimize ART regimen.
• Note: Ganciclovir ocular implants are no longer commercially available

• 3.4 ARN (Acute retinal necrosis)

• Preferred regimen: Acyclovir 10-15 mg/kg IV q8h for 10–14 days, followed by Valacyclovir 1 g PO tid for 6 weeks AND Ganciclovir 2 mg/0.05mL intravitreal qd/bid twice weekly
• Note: Duration of therapy is not well defined and should be determined based on clinical, virologic, and immunologic response in consultation with experienced ophthalmologist

• 4 Prevention of varicella zoster virus (VZV) Infections in HIV-Infected Adults and Adolescents

• 4.1 Pre-Exposure Prevention of VZV Primary Infection

• Indications

• Adult and adolescent patients with CD4 count ≥200 cells/mm3 without documentation of vaccination, health-care provider diagnosis or verification of a history of varicella or herpes zoster, laboratory confirmation of disease, or persons who are seronegative for VZV. Routine VZV serologic testing in HIV-infected adults and adolescents is not recommended.
• Vaccination
• Primary varicella vaccination (Varivax™), 2 doses (0.5 mL SQ) administered 3 months apart
• If vaccination results in disease because of vaccine virus, treatment with acyclovir is recommended.
• VZV-susceptible household contacts of susceptible HIV-infected persons should be vaccinated to prevent potential transmission of VZV to their HIV-infected contacts.
• If post-exposure VariZIG has been administered, wait at least 5 months before varicella vaccination.
• If post-exposure acyclovir has been administered, wait at least 3 days before varicella vaccine.

• 4.2 Post-Exposure Prophylaxis

• Indication

• Close contact with a person who has active varicella or herpes zoster, and
• Is susceptible to VZV (i.e., has no history of vaccination or of either condition, or is known to be VZV seronegative)

• Preferred regimen: VariZIG 125 IU /10 kg (maximum of 625 IU) IM, administered as soon as possible and within 10 days after exposure to a person with active varicella or herpes zoster
• Alternative regimen (Begin 7–10 Days After Exposure): Acyclovir 800 mg PO 5 times/day for 5–7 days OR Valacyclovir 1 g PO tid for 5–7 days
• If post-exposure VariZIG has been administered, wait at least 5 months before varicella vaccination.
• Note: Patients receiving monthly high dose IVIG (i.e., >400 mg/kg) are likely to be protected against VZV and probably do not require VariZIG if the last dose of IVIG was administered <3 weeks before VZV exposure.
• Note: Neither these pre-emptive interventions nor post-exposure varicella vaccination have been studied in HIV-infected adults and adolescents.
• If acyclovir or valacyclovir is used, varicella vaccines should not be given until at least 72 hours after the last dose of the antiviral drug.

Influenza

• Influenza virus Return to Top

• Antiviral Medications Recommended for Treatment of Influenza

• 1. Adults

• Preferred regimen (1): Oseltamivir (Tamiflu®) 75 mg PO bid for 5 days
• Preferred regimen (2): Zanamivir (Relenza®) 10 mg (two 5-mg inhalations) bid for 5 days
• Preferred regimen (3): Peramivir (Rapivab®) 600 mg IV for 15-30 minutes (single dose)
• Note: FDA approved and recommended Peramivir (Rapivab®) for use in adults ≥18 yrs

• 2. Children

• 2.1 Children < 1 yr

• Preferred regimen: Oseltamivir (Tamiflu®) 3 mg/kg/dose PO bid for 5 days

• 2.2 Children > 1 yr

• 2.2.1 Children ≤ 15 kg

• Preferred regimen: Oseltamivir (Tamiflu®) 30 mg PO bid for 5 days

• 2.2.2 Children > 15 to 23 kg

• Preferred regimen: Oseltamivir (Tamiflu®) 45 mg PO bid for 5 days

• 2.2.3 Children > 23 to 40 kg

• Preferred regimen: Oseltamivir (Tamiflu®) 60 mg PO bid for 5 days

• 2.2.4 Children > 40 kg

• Preferred regimen (1): Oseltamivir (Tamiflu®) 75 mg PO bid for 5 days
• Preferred regimen (2): Zanamivir (Relenza®) 10 mg (two 5-mg inhalations) bid for 5 days, may be considered for children > 7 yrs old

• 3. Adult Patients with Renal Impairment or End Stage Renal Disease (ESRD) on Dialysis

• 3.1 Oseltamivir

• Creatinine clearance 61 to 90 mL/min-75 mg PO bid for 5 days
• Creatinine clearance 31 to 60 mL/min-30 mg PO bid for 5 days
• Creatinine clearance 10 to 30 mL/min-30 mg PO qd for 5 days
• ESRD Patients on Hemodialysis
• Creatinine clearance ≤10 mL/min-30 mg after every hemodialysis cycle. Treatment duration not to exceed 5 days
• ESRD Patients on Continuous Ambulatory Peritoneal Dialysis-A single 30 mg dose administered immediately after a dialysis exchange

• 3.2 Peramivir

• Creatinine clearance >50 mL/min-600mg IV single dose
• Creatinine clearance 30 to 49 mL/min-200mg IV single dose
• Creatinine clearance 10 to 29 mL/min-100mg IV single dose
• ESRD Patients on Hemodialysis-Dose administered after dialysis at a dose adjusted based on creatinine clearance
• Note: No dose adjustment is recommended for inhaled zanamivir for a 5-day course of treatment for patients with renal impairment.

• 4. Antiviral Medications Recommended for Chemoprophylaxis of Influenza

• 4.1. Adults

• Preferred regimen (1): Oseltamivir (Tamiflu®) 75 mg PO qd for 7days
• Preferred regimen (2): Zanamivir (Relenza®) 10 mg (two 5-mg inhalations) qd for 7 days

• 4.2. Children

• 4.2.1 Children < 1 yr

• Preferred regimen: Oseltamivir (Tamiflu®) 3 mg/kg/dose PO qd for 7 days

• 4.2.2 Children > 1 yr

• 4.2.2.1 Children ≤ 15 kg

• Preferred regimen: Oseltamivir (Tamiflu®) 30 mg PO qd for 7 days

• 4.2.2.2 Children > 15 to 23 kg

• Preferred regimen: Oseltamivir (Tamiflu®) 45 mg PO qd for 7 days

• 4.2.2.3 Children > 23 to 40 kg

• Preferred regimen: Oseltamivir (Tamiflu®) 60 mg PO qd for 7 days

• 4.2.2.4 Children > 40 kg

• Preferred regimen (1): Oseltamivir (Tamiflu®) 75 mg PO qd for 7 days
• Preferred regimen (2): Zanamivir (Relenza®) 10 mg (two 5-mg inhalations) qd for 7 days, may be considered for children > 7 yrs older
• Note: If child is < 3 months old, use of Oseltamivir for chemoprophylaxis is not recommended unless situation is judged critical due to limited data in this age group.