4.12 - Human Immunodeficiency Virus Related Opportunistic Infection

Disease / Etiology

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Pneumocystis Jirovecii (Carinii) Pneumonia (PCP)


Moderate to Severe Disease
Trimethoprim / Sulfamethoxazole
(TMP / SMX)
TMP 15 - 20 mg/kg/day IV divided q6 - 8H for 21 days, may switch to PO after clinical improvement

Mild to Moderate Disease TMP - SMX (TMP 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

 
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
Dapsone 100 mg PO q24H
+ TMP 15 mg/kg/day PO (3 divided doses)

Severe Disease (PaO2 < 70 mmg Hg)
Pentamidine 4 mg/kg IV q24H infused over > 60 mins
 
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
To be discontinued in patients on HAART with CD4 > 200 with undetectable viral loads for 3 - 6 months.
 
Secondary Prophylaxis
Indications: Hx of PCP, CD4 < 200 or < 14%

TMP - SMX (TMP 80 mg / SMX 400 mg) 1 - 2 tablets PO q24H

 
Dapsone 100 mg PO q24H
OR
Aerolized Pentamidine 300 mg every month via Respigard II nebulizer

 


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 (M, W, F). Under 6 months old: 
Co-trimoxazole 20 mg (Trimethoprim component) PO q24H.



Toxoplasma gondii encephalitis
 
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 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

TMP - SMX (TMP 5 mg/kg) IV/PO q12H
 
If Pyrimethamine not available, use Fansidar. 
1 tab Fansidar (Sulfadoxine / Pyrimethamine) contains 25 mg of Pyrimethamine.

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.

Dexamethasone 4 mg q6H and taper down over next few days (Jayawardena at al, Hospital Physician 2008).

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.
 
Secondary Prophylaxis

Pyrimethamine 25 – 50 mg PO q24H
+ Sulfadiazine 0.5 - 1 gm PO q6H
+ Folinic Acid 15 mg PO q24H

 
Pyrimethamine 25 – 50 mg PO q24H
+ Clindamycin 600 mg PO q8H
+ Folinic Acid 15 mg PO q24H

OR

TMP - SMX
(80 mg / 400 mg)
2 tablet PO q12H

 
Cryptococcal Meningitis

(Cryptococcus neoformans var neoformans)

Induction Therapy
Amphotericin B Deoxycholate 0.7 mg/kg IV q24H
+ Flucytosine (if available) 25 mg/kg PO q6H
for at least 2 weeks
OR
Lipid formulation Amphotericin B 4 – 6 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 + (if available) Flucytosine 25 mg/kg IV q6H for at least 2 weeks

 
Induction Therapy
Fluconazole 400 – 800 mg IV/PO q24H
+ Flucytosine 25 mg/kg PO q6H for 4 – 6 weeks for persons unable to tolerate or unresponsive to Amphotericin B
 
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.

Consolidation Therapy
(after at least 2 weeks of successful induction – defined as significant clinical improvement & negative CSF culture)
Fluconazole 400 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

 
Consolidation Therapy
Itraconazole 200 mg PO q12H for 8 weeks
 
Secondary Prophylaxis
 
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.

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

 
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
 
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).
 
Suppressive Therapy
Ganciclovir 6 mg/kg IV daily 5 times weekly
OR
Valganciclovir 900 mg PO q24H

 
Suppressive Therapy
Foscarnet 120 mg/kg IV daily 5 times weekly

Extraocular CMV Disease (CMV colitis, Esophagitis, Pneumonitis)

Ganciclovir 5 mg/kg IV q12H for 21 - 28 days or until resolution of signs and symptoms.

 
Foscarnet 90 mg/kg IV q12H

Maintenance therapy is usually not necessary.
 HAART offers best hope for prevention of relapses.
 
Mycobacterium Avium Complex (MAC)

At least 2 drugs as initial therapy with:
Clarithromycin 500 mg PO q12H
+ Ethambutol 15 mg/kg PO q24H

Addition of rifabutin may also be considered: Rifabutin 300 mg 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

 
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

 
Discontinuation
Consider if patient is on HAART and viral load well suppressed, CD4 > 100 > 3 months, asymptomatic of MAC, and has completed > 3 months of MAC treatment.

Rifabutin is not available in UMMC, may substitute with Rifampicin.

Avoid Fluoroquinolones wherever possible in patients < 18 years old

 
Penicilliosis
Penicilium marneffei
 
Induction Regimen
Amphotericin B Deoxycholate 0.6 mg/kg IV q24H for 2 weeks

Continuation Phase
Itraconazole 200 mg PO q12H for 10 weeks

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


In less severe disease: Itraconazole 200 mg PO q8H for 3 days, then 200 mg PO q12H for 12 weeks, then 200 mg q24H.
 
Consider discontinuation among patients with CD4 count > 100 cells/mm3 for > 6 months.

Itraconazole syrup has better bioavailability compared to Itraconazole capsule.

Tuberculosis
Mycobacterium tuberculosis
 
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

 

Drug Daily Dose (Range) (mg/kg)
Max
Daily
Dose
(mg)
INH 5 (4-6)
300

RIF

10
(8-12)

600

PZA

25
(20-30)

2000

EMB

15
(15-20)

1600

Strep

15
(12-18)

1000

 

Fixed Dose Combinations (FDC) available:
Akurit 4
(RIF 150 mg, INH 75 mg, PZA 400 mg, EMB 275 mg)

Akurit 2
(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

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


Drug
Daily Dose
Range
(mg/kg)
Max
Daily
Dose
(mg)
INH
(H)
10 - 15 300
RIF
(R)
10 - 20 600
PZA
(Z)
20 - 40 2000
EMB
(E)
15 - 25 1000

 






Treatment of drug resistant active TB
Resistant to INH
RIF + EMB + PZA for 6 months
or
RIF + EMB for 12 months (with PZA for the first 2 months)

A Fluoroquinolone may strengthen the regimen for patients with extensive disease .

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.

 
Directly Observed Therapy (DOT) is recommended for all patients.
All patients should receive pyridoxine 10 - 25 mg PO q24H supplementation.

All HIV - TB co-infected patients should receive co-trimoxazole preventive therapy for the duration of TB treatment (WHO 2010).

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 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.
RFP 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. If rifabutin is not available, options are to omit rifampicin and prolong the duration of treatment, or increase dose of ritonavir in ritonavir boosted PIs, or to sustitute PI for raltegravir.