3.12 - Human Immunodeficiency Virus Related Opportunistic Infection (Updated)

Disease / Etiology

Pneumocystis Jirovecii (Carinii) Pneumonia (PCP)

Preferred

Alternative

Comments

Tuberculosis

Mycobacterium tuberculosis

Talaromycosis (Formerly Penicilliosis)

Talaromyces marneffei

Mycobacterium Avium Complex (MAC)

CMV neurological disease

CMV esophagitis or colitis

Cytomegalovirus (CMV) Retinitis

Secondary Prophylaxis

Cryptococcal Meningitis

(Cryptococcus neoformans var neoformans)

Secondary Prophylaxis

Toxoplasma gondii encephalitis

Secondary Prophylaxis

Indications: Hx of PCP, CD4 < 200 or < 14%

Fixed Dose Combinations (FDC) available:

Akurit 4 contains

(RIF 150 mg, INH 75 mg, PZA 400 mg, EMB 275 mg)

Akurit 2 contains

(RIF 150 mg, INH 75 mg)

30 - 37 kg: 2 tablets daily

38 - 54 kg: 3 tablets daily

55 - 70 kg: 4 tablets daily

> 70 kg: 5 tablets daily

AND

Pyridoxine 10 - 50mg PO q24H

Duration of therapy:

Pulmonary TB for 6 months.

Extrapulmonary TB with CNS, bone or joint infections for 9 - 12 months.

Extrapulmonary TB in other sites for 6 - 9 months.

Paediatric:

Pulmonary TB

HRZ(E) for 2 months,

followed by HR for 7 months

Osseous or CNS TB

HRZE for 2 months,

followed by HR for 10 months or longer

Moderate to Severe Disease

Co-trimoxazole (Trimethoprim component) 15 - 20 mg/kg/day IV divided q6 - 8H for 21 days, may switch to PO after clinical improvement

Mild to Moderate Disease

Co-trimoxazole (Trimethoprim component) 15 - 20 mg/kg/day PO divided q8H for 21 days

Paediatric:

Co-trimoxazole 5 mg/kg (Trimethoprim component) IV/PO q6H for 21 days

Co-trimoxazole (480 mg) 1 - 2 tablets PO q24H

Primary Prophylaxis in Children:

Co-trimoxazole 4 mg/kg (Trimethoprim component) PO q24H. Primary prophylaxis starts from 6 weeks old in HIV-exposed infants until status is established.

Alternative regimes:

150 mg/m2/day (Trimethoprim component) in 2 divided doses, given on alternate days (Monday, Wednesday, Friday). Under 6 months old:

Co-trimoxazole 20 mg (Trimethoprim component) PO q24H.

Pyrimethamine loading dose 200 mg PO single dose

followed by

Pyrimethamine 50 mg

(< 60 kg) to 75 mg (≥ 60 kg) PO q24H

+ Sulfadiazine 1 gm (< 60 kg) to 1.5 gm (≥ 60 kg) PO q6H

+ Folinic Acid 15 mg PO q24H

For at least 6 weeks

Longer duration if clinical or radiological disease is extensive or response is incomplete at 6 weeks.

Paediatric:

Pyrimethamine 2 mg/kg/day (Day 1 & 2) PO loading dose; followed by 1 mg/kg/day for 2 - 6 months and then 1 mg/kg/day 3 times per week to complete 12 months total duration.

+ Sulfadiazine 50 mg/kg/dose PO q12H for 12 months

+ Folinic Acid 10 - 25 mg PO daily with each dose of Pyrimethamine.

Continue for 1 week after discontinuation of Pyrimethamine.

Pyrimethamine 25 – 50 mg PO q24H

+ Sulfadiazine 0.5 - 1 gm PO q6H

+ Folinic Acid 15 mg PO q24H

Induction Therapy

Amphotericin B Deoxycholate 0.7 - 1 mg/kg IV q24H

OR

Lipid formulation Amphotericin B 5 mg/kg IV daily (consider in those with renal dysfunction on therapy or have high likelihood of renal failure)

+

Flucytosine 25 mg/kg PO q6H

for at least 2 weeks *

Paediatric:

Amphotericin B Deoxycholate 0.7 - 1.5 mg/kg IVI q24H over 4 - 6 hours for at least 2 weeks

+

Flucytosine (if available) 25 mg/kg PO q6H for at least 2 weeks

Consolidation Therapy

(after at least 2 weeks of successful induction – defined as significant clinical improvement & negative CSF culture)

Fluconazole 800 mg PO q24H for 8 weeks

Paediatric:

Fluconazole 6 mg/kg IV/PO q12H (800 mg/day) for 8 - 10 weeks

OR Itraconazole 5 mg/kg (max 200 mg) q12hr PO for 8 weeks

Fluconazole 200 mg PO q24H until CD4 count > 200 with undetectable viral loads.

Paediatric:

Fluconazole 3 - 6 mg/kg PO q24H (max 200 mg/day).

May be stopped when CD4 > 200.

Initial Therapy

Ganciclovir 5 mg/kg IV q12H for 2 - 3 weeks

Paediatric:

5 mg/kg IV q12H for 2 - 3 weeks

OR

Valganciclovir 900 mg PO q12H for 2 - 3 weeks

Paediatric:

16 mg/kg PO q12H for 2 - 3 weeks

Immediate Sight Threatening Lesions

Intravitreal Ganciclovir may be administered with consideration of placement of Ganciclovir intraocular implant provide more expedient loading doses and in patients unable to tolerate systemic therapy.

Chronic Maintenance Therapy

Ganciclovir 6 mg/kg IV daily 5 times weekly

OR

Valganciclovir 900 mg PO q24H

Ganciclovir 5 mg/kg IV q12H

OR Valganciclovir 900mg PO q12H

for 21 - 42 days or until resolution of signs and symptoms.

Ganciclovir 5 mg/kg IV q12H

AND

Foscarnet 90 mg/kg IV q12h or 60 mg/kg IV q8h (if available)

Continue until CMV PCR has become undetectable in both CSF and serum and clinical evidence of disease has resolved.

At least 2 drugs as initial therapy with:

Clarithromycin 500 mg PO q12H

+ Ethambutol 15 mg/kg PO q24H

Addition of rifabutin or rifampicin may also be considered: Rifabutin 300 mg PO q24H or Rifampicin 10mg/kg PO q24H.

Paediatric:

Ethambutol 15 - 25 mg/kg PO q24H (max 1.2 gm/day)

+

Clarithromycin 7.5 - 10 mg/kg (max 500 mg) PO q12H

OR Azithromycin 10 - 12 mg/kg (max 500 mg/day) PO q24H

Induction Regimen

Amphotericin B Deoxycholate 0.6 mg/kg IV q24H for 2 weeks

OR

Lipid formulation Amphotericin B 5 mg/kg IV q24H (consider in those with renal dysfunction on therapy or have high likelihood of renal failure)

Continuation Phase

Itraconazole 200 mg PO q12H for 10 weeks

Chronic Maintenance Therapy

Itraconazole 200 mg PO q24H

Paediatric:

Amphotericin B Dexoycholate 0.6 - 1 mg/kg IV q24H for 14 days, followed by Itraconazole 3 - 5 mg/kg (max 200 mg) PO q24H

Empirical treatment should be initiated and continued in whom TB is suspected until all diagnostic work up is complete.

Treatment of drug susceptible active TB disease:

Initial Phase (2 months)

Isoniazid (INH) + Rifampicin (RIF) + Pyrazinamide (PZA) + Ethambutol (EMB)

Continuation phase

INH + RIF daily

Moderate to Severe Disease

Clindamycin [600 mg IV q6H] or [450 mg PO q6H or 600 mg PO q8H]

+ Primaquine 30 mg base PO q24H for 21 days

OR

Pentamidine 4 mg/kg IV q24H infused over > 60 mins

Dapsone 100 mg PO q24H

OR

Nebulized Pentamidine 300 mg every month

Pyrimethamine loading dose 200 mg PO single dose

followed by

Pyrimethamine 50 mg

(< 60 kg) to 75 mg (≥ 60 kg) PO q24H

+ Folinic Acid 15 mg PO q24H

+ Clindamycin 600 mg IV/PO q6H

OR

Co-trimoxazole (Trimethoprim component) 5 mg/kg IV/PO q12H

Pyrimethamine 25 – 50 mg PO q24H

+ Clindamycin 600 mg PO q8H

+ Folinic Acid 15 mg PO q24H

OR

Co-trimoxazole (480 mg)

2 tablets PO q12H

Induction Therapy

Fluconazole 1200 mg IV/PO q24H

+ Flucytosine 25 mg/kg PO q6H for 2 weeks for persons unable to tolerate or unresponsive to Amphotericin B

Itraconazole 200 mg PO q12H until CD4 > 200 (for patients intolerant of or who failed Fluconazole).

Initial Therapy

Foscarnet 90 mg/kg IV q12H for 2 - 3 weeks

Paediatric:

Foscarnet 60 mg/kg IV q8H for 14 - 21 days, then 90 - 120 mg/kg q24H for chronic suppressive therapy

Chronic Maintenance Therapy

Foscarnet 120 mg/kg IV daily 5 times weekly

Foscarnet 90 mg/kg IV q12H

Valganciclovir 900mg PO q12H

Azithromycin 500 mg PO q24H

+ Ethambutol 15 mg/kg PO q24H

Addition of a 3rd or 4th drug should be considered for patients with advanced immunosuppression (CD4 count < 50) or in the absence of effective ART.

Amikacin 10 – 15 mg/kg IV q24H

OR Streptomycin 15 mg/kg (max 1 gm) IV / IM q24H

OR

Levofloxacin 500 mg PO q24H OR Moxifloxacin 400 mg PO q24H

Paediatric:

Ciprofloxacin 10 - 15 mg/kg PO q12H (max 1500 mg/day)

+ Amikacin 15 - 30 mg/kg/day IV or IM

Voriconazole 6 mg/kg IV q12H for 1 day, then 4 mg/kg IV/PO q12H for 2 weeks

Treatment of drug resistant active TB

Resistant to INH

RIF + EMB + PZA+ Levofloxacin for 2 months, followed by RIF + EMB + Levofloxacin 750mg PO q24H for 7 months

Resistant to RIF

INH + PZA + EMB + Fluoroquinolone for 2 months,

followed by 10 - 16 additional months with INH + EMB + Fluroquinolone

Multidrug Resistant (MDR) or Extensively Drug Resistant (XDR) TB

Therapy should be individualized based on resistance pattern and with close consultation with an ID specialist.

Indication for steroids

PaO2 < 70 mmg Hg (9.3kPa) or SpO2 < 92% on room air.

Prednisolone doses (beginning as early as possible and within 72 hours of PCP therapy):

Days 1 - 5: 40 mg PO q12H

Days 6 - 10: 40 mg PO q24H

Days 11 - 21: 20 mg PO q24H

If unable to take oral, methylprednisolone at 75% of this dose can be administered.

Paediatric:

Prednisolone: PaO2 < 70 mmg Hg in room air

Start 1.5 - 2 mg/kg/day in 2 divided doses

Tail down by 1 mg/kg/day every 5 days over 10 - 12 days

OR Dexamethasone 0.3 - 0.5 mg/kg IM/IV q6H for 5 days

OR alternatively

Methylprednisolone

Patients given dapsone should be tested for G6PD deficiency.

Discontinuation of secondary/ primary prophylaxis

Can be discontinued in patients on HAART with CD4 >100 with undetectable viral loads for 3 - 6 months.

If Pyrimethamine not available, to use Co-Trimoxazole as above.

Adjunctive corticosteroids (e.g. Dexamethasone) should be administered when clinically indicated, e.g. for treatment of a mass effect associated with focal lesions or associated oedema. Discontinue as soon as clinically feasible.

If clindamycin is used in place of sulfadiazine, additional therapy must be added to prevent PCP.

Paediatric:

Transmission of toxoplasma to infants by mother with HIV is uncommon in early pregnancy (< 10%). However, the risk increases sharply if mother has toxoplasma infection during last few weeks of pregnancy. Toxoplasma encephalitis in HIV-infected children is uncommon. Congenital toxoplasmosis is diagnosed by presence in neonatal blood of toxoplasma specific IgA, IgM in the first 6 month of life; or persistence of toxoplasma specific IgG beyond 6 month old.

Co-trimoxazole NOT used in children as treatment.

Discontinuation

Consider when on HAART, CD4 > 200 for more than 3 months and viral load suppressed.

* A 1 week course of Amphotericin B Deoxycholate with Flucytosine is permissible if access to lipid formulation Amphotericin B is limited and if a patient is developing severe toxicity to Amphotericin B Deoxycholate. However, this has to be followed by PO Fluconazole 1200mg/day for the remainder of the induction phase which is 2 weeks.

Addition of Flucytosine to Amphotericin B has been associated with more rapid sterilization of CSF, decreased risk for subsequent relapse and reduced mortality.

OP should always be measured when an LP is performed. If OP > 250 mm H2O and signs of cerebral oedema present, do daily LPs to reduce CSF pressure.

If clinical signs of cerebral oedema do not improve after about 2 weeks of daily LPs, consider placement of a lumbar drain or ventriculoperitoneal shunt.

Initial therapy should also include optimization of HAART.

Maintenance therapy for CMV retinitis can be safely discontinued in patients with inactive disease and sustained CD4+ count (>100 cells/mm3 for ≥ 3 – 6 months) and undetectable viral loads.

Patients with CMV retinitis who discontinued maintenance therapy should undergo regular eye examination, optimally every 3 months, for early detection of relapse or immune recovery uveitis (IRU).

Foscarnet is not available in UMMC formulary.

Maintenance therapy is usually not necessary.

HAART offers best hope for prevention of relapses.

Foscarnet is not available in UMMC formulary.

Discontinuation

At least 12 months of therapy, can discontinue if no signs and symptoms of MAC disease and sustained (>6 months) CD4 count >100 cells/mm3 in response to ART.

Avoid Fluoroquinolones wherever possible in patients < 18 years old

Consider discontinuation among patients with CD4 count > 100 cells/mm3 for > 6 months.

Itraconazole syrup has better bioavailability compared to Itraconazole capsule.

Directly Observed Therapy (DOT) is recommended for all patients.

All patients should receive pyridoxine 10 - 50 mg PO q24H supplementation.

All HIV - TB co-infected patients should receive co-trimoxazole preventive therapy for the duration of TB treatment.

Adjuvant corticosteroids should be added when treating CNS and pericardial disease.

Recommended corticosteroid regimens:

Dexamethasone 0.3 - 0.4 mg/kg tapered over 6 - 8 weeks or

Prednisolone 1 mg/kg for 3 weeks then tapered over 3 - 5 weeks.

Daily dosing of anti-TB treatment is preferred for HIV infected patients in intensive phase.

Intermittent dosing in intensive phase: 5 days per week for 40 doses by DOT may be considered.

Rifampicin is not recommended in patients receiving protease inhibitors (PI) because of induction of PI metabolism.

Rifabutin is preferred in patients receiving PIs as it is a less potent inducer of CYP 3A4.

Rifabutin dose when given with PIs: 150mg PO q24H

Revision history: Updated on 9th Feb 2021

Candidiasis (Mucocutaneous)

Topical azoles (Clotrimazole OR Miconazole) for 3–7 days

Oral fluconazole 150 mg for 1 dose, or

Uncomplicated Vulvo-Vaginal Candidiasis:

Fluconazole 100 mg (up to 400 mg) PO or IV q24

Oesophageal Candidiasis (For 14–21 Days):

Topical Therapy: Nystatin suspension 4–6 mL q6H or 1–2 flavoured pastilles 4–5 times daily

Oral Therapy: Fluconazole 100 mg PO q24H

Oropharyngeal Candidiasis; Initial Episodes (For 7–14 Days):

Oral Therapy

Itraconazole 200 mg PO daily