HIV-ASSOCIATED OPPORTUNISTIC INFECTIONS – PCT IV SPRING 2020

THE BUGS – TREATMENT OF ACUTE INFECTION

CD4 Most
Opportunistic
Likely to Typical Clinical Presentation Preferred Treatment Regimens Alternative Treatment Regimens Clinical Pearls
Infection
Occur
Alternative or adjunctive topicals:
Painless, creamy white, plaque- Usually caused by
Oral Clotrimazole troches 5x/day or
like lesions on tongue or mucosal Fluconazole 100 mg PO QD x 1 – 2 wks Candida albicans, which
Candidiasis Nystatin suspension 4x/day swish &
surface of mouth is usually susceptible to
swallow
CD4 < 500 fluconazole
Similar plaques to oral candidiasis Above topicals should not be used
Esophageal Fluconazole 200 mg (acceptable range: Fluconazole is rough on
demonstrated in esophagus  alone for esophageal candidiasis. Can
Candidiasis 100 – 400 mg) QD x 2 – 3 wks the liver!
results in odynophagia, dysphagia be used as adjunctive therapy

70-80% of patients with

Mild-moderate: TMP/SMX 15-20 Mild-moderate: Primaquine +
Insidious onset w/ progressive AIDS developed PCP;
Pneumocystis mg/kg/day PO in 3 div’d. doses x 21 d Clindamycin, Atovaquone, Dapsone +
dyspnea, +/- productive cough
jirovecii TMP
CD4 < 200 and elevated WBC, fever, ↑LDH; Most cases occur in
(carinii) Moderate-severe: TMP/SMX 15-20
Lung radiology shows diffuse patients unaware of
pneumonia mg/kg/day IV in 3-4 div’d. doses x 21 d + Moderate-severe: Primaquine +
“ground glass” opacities status or not receiving
prednisone taper within 72 h Clindamycin, Inhaled Pentamidine
care
Empiric Dx often
Induction Phase: Pyrimethamine 200 mg PO once, followed by wt-based dosing: confirmed by response
- < 60 kg: Pyrimethamine 50 mg PO daily + Leucovorin 10-25 mg PO daily + to TE therapy
Focal encephalitis (most
Sulfadiazine 1000 mg PO Q6H
Toxoplasmosis common) – HA, confusion, motor
- > 60 kg: Pyrimethamine 75 mg PO daily + Leucovorin 10-25 mg PO daily + Infection occurs after
gondii CD4 < 50-100 weakness, fever;
Sulfadiazine 1500 mg PO Q6H eating undercooked
encephalitis CT scan shows ring-enhancing
meat, raw shellfish, or
lesions
Maintenance Phase: After at least 6 wks of therapy, continue w/ pyrimethamine + handling cat feces
leucovorin + sulfadiazine until asymptomatic and CD4 > 200 for 6 months
Think “PLS”
Subacute meningitis or
CD4 < 100; meningoencephalitis w/ fever, Induction phase: Liposomal amphotericin B + flucytosine x at least 2 wks
Greatest risk malaise, HA;
Cryptococcus
for brain Neck stiffness, photophobia; Consolidation Phase: Fluconazole 400 mg PO/IV once daily x at least 8 wks
neoformans
dissemination If increased ICP, skin lesions
if < 50 mimicking molluscum Maintenance Phase: Fluconazole 200 mg PO x at least 1 year
contagiosum

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 Initial treatment: Ethambutol 15 mg/kg PO once daily + Macrolide (Clarithromycin
500 mg PO BID or Azithromycin 500-600 mg PO once daily)
Add 3rd or 4th drug if: CD4 < 50, high mycobacterial load, or absence of effective
Mycobacteriu Persistent fever, night sweats,
ART Think “add a MACrolide
m avium CD4 < 50 wt. loss, fatigue, diarrhea, abd.
- Rifabutin 300 mg PO daily or for MAC”
Complex (MAC) pain, anemia, ↑ Alk Phos
- Levofloxacin 500 mg PO daily or
- Moxifloxacin 400 mg PO daily or
- Amikacin 10-15 mg/kg IV daily

THE BUGS – PROPHYLAXIS

Primary Primary Prophylaxis Clinical Pearls
Preferred Prophylaxis
Opportunistic Infection Prophylaxis Indication to Alternative Prophylaxis Regimens
Regimens
Indication to Start Discontinue
Oral Candidiasis
(Thrush) NOT recommended
Esophageal Candidiasis
 TMP-SMX 1 DS PO MWF Bactrim 1 SS or 1 DS Daily = pref
 Atovaquone 1500 mg PO QD Alternatives:
CD4 ≥ 200 for ≥ 3
Pneumocystis jiroveci CD4 count < 200 or TMP-SMX 1 DS or 1 SS  Dapsone 100 mg PO QD Dapsone
months in response to
(carinii) pneumonia CD4 % < 14% tablet PO once daily  Aerosolized pentamidine 300 mg via Atovaquone
ART
Respigard II nebulizer Q month Pentamidine

Toxoplasmosis gondii CD4 count < 100 + CD4 ≥ 200 for ≥ 3

TMP-SMX 1 DS PO daily N/A
encephalitis Toxo IgG (+) months with ART

Cryptococcus
NOT Recommended
neoformans

ART + Bactrim for

Mycobacterium avium CD4 > 100 for ≥ 3 PCP/Toxo +  Clarithromycin 500 mg PO BID
CD4 count < 50
Complex (MAC) months Azithromycin 1200 mg  Azithromycin 600 mg PO twice weekly
PO once weekly

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 THE DRUGS
MOA
Alters cellular membranes
resulting in increased
membrane permeability,
leakage of potassium and
Fluconazole amino acids, and impaired
uptake of purine and
pyrimidine precursors to DNA;
Usually fungistatic
SMX: inhibits dihydrofolic acid
formation  interferes w/
bacterial folic acid synthesis
TMP-SMX
(Bactrim; Septra) TMX: Inhibits dihydrofolic acid
reduction  inhibition of
enzymes in the folic acid
pathway
Competitive antagonist of
para-aminobenzoic acid
Dapsone (PABA)  prevents normal
bacterial utilization of PABA
 inhibits folic acid synthesis
Inhibits electron transport in
Atovaquone mitochondria  inhibits
synthesis of nucleic acids, ATP
Reversibly binds to 50S
Clindamycin ribosomal subunit  inhibits
bacterial protein synthesis
Inhibits oxidative
phosphorylation of
Pentamidine
nucleotides and nucleic acids
into RNA and DNA
Dosing & Duration of Therapy
Candidiasis
Thrush/oropharyngeal: fluconazole
100 mg POvQD daily x 1 – 2 weeks
Esophageal: fluconazole 200 mg PO
QD x 2 – 3 weeks
Vulvovaginal: fluconazole 150 mg PO
x 1 dose
PCP/PJP
Mild-moderate: TMP/SMX 15-20
mg/kg/day PO in 3 divided doses x
21 days
Moderate-severe: TMP/SMX 15-20
mg/kg/day IV in 3-4 divided doses x
21 days + prednisone taper within 72
hours
PCP PPx: 100 mg once daily
PCP Tx: 100 mg once daily (+ TMP 15
mg/kg/day divided into 3 doses)
Atovaquone 750 mg BID OR
Atovaquone 1500 mg once daily
(same for Tx + PPx)
Not recommended for PCP PPx;
PCP Tx: Clindamycin [IV 600 mg Q6H
or 900 mg Q8H] or [PO 450 mg Q6H
or 600 mg Q8H] + primaquine
PCP PPx: 300 mg inhaled once daily
PCP Tx: 4 mg/kg IV once daily x 21
days  IV should NOT be used to
treat PCP (limited efficacy)
Adverse Effects
Common Adverse Effects: ↑AST 20%, QTc
prolongation, GI (nausea 3.7%, abdominal
pain 1.7%, vomiting 1.7%, diarrhea 1.5%),
headache 1.9%, skin rash 1.8%, alopecia
Rare Adverse Effects: severe hepatotoxicity,
exfoliative dermatitis
Rash (30-55%), fever (30-40%), leukopenia
(30-40%), thrombocytopenia (15%), azotemia,
increased LFTs, hepatitis, nephrotoxicity,
hyperkalemia
Rash, fever, nausea, methemoglobinemia
(may present as fatigue, decreased RBC, SOB,
incr. HR, bluish lips and fingernails),
decreased WBCs, sulfone syndrome (fever,
rash, jaundice, enlarged liver)
Rash, N/V/D, HA, dizziness, itchiness, fever,
increased LFTs
Diarrhea (dose dependent), N/V, anorexia,
rash, metallic taste
Nephrotoxicity, hypo/hyperglycemia,
orthostatic hypoTN (if infused too rapidly),
N/V, ↓ Ca, Mg, K, WBCs, PLTs; pancreatitis,
hepatitis, fever, rash, confusionhallucinations,
bronchospasm, metallic taste (if inhaled)
Clinical Pearls
IV dose = PO dose because high oral
bioavailability
Drug-Drug Interactions: Fluconazole
is an inhibitor of CYP2C9 (potent) and
CYP3A4 (moderate) whose effects
persist for 4 – 5 days after completing
therapy due to fluconazole’s long half-
life
TMP/SMX dosed from TMP component
(SS = 80 mg TMP; DS = 160 mg TMP)
Sulfamethoxazole = nephrotoxic @
high doses via interstitial nephritis
Trimethoprim inhibits tubular
creatinine secretion = ↑SCr
(reversible)
MUST CHECK G6PD STATUS BEFORE
STARTING
If G6PD deficient, do not use  may
lead to hemolytic anemia
Suspension has unpalatable taste that
often results in poor compliance, $$$;
Take w/ a high fat meal
High risk for causing Clostridium
difficile infection via altering GI
microflora
Data insufficient to recommend
administering pentamidine by
nebulization devices other than
Respigard II nebulizer
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Disrupts mitochondria and
Primaquine
binds to DNA
Inhibits parasitic dihydrofolate
Pyrimethamine
reductase  inhibits
(Daraprim)
tetrahydrofolic acid synthesis
Active metabolite of folic acid
Leucovorin and an essential coenzyme for
nucleic acid synthesis
Interferes w/ bacterial growth
by inhibiting folic acid
Sulfadiazine
synthesis through competitive
antagonism of PABA
Amphotericin B Binds to ergosterol  alters
deoxycholate; cell membrane permeability
 leakage of cell components
Liposomal  cell death; may also
Amphotericin B stimulate macrophages
Converted to fluorouracil
which competes w/ uracil 
Flucytosine (5-FC)
interferes w/ fungal RNA and
protein synthesis
15-30 mg primaquine base PO once
daily with food (+ clindamycin)
Toxoplasmic Encephalitis
Induction phase: LD of 200 mg x 1
dose, then 50-75 mg PO QD for at
least 6 wks
Maintenance phase: Followed by
25-50 mg PO QD as chronic
maintenance Tx
Induction phase: 1-1.5 g PO Q6H for
6 wks
Maintenance phase: Followed by 0.5
– 1 g PO Q6H
Cryptococcal Meningitis
0.7 – 1 mg/kg IV once daily
Liposomal Amphotericin B 3-4 mg/kf
IV once daily
Flucytosine 25 mg/kg QID
Requires renal dose adjustment in
pts w/ CrCl < 40 mL/min OR reduce
dose 50% for every 50% CrCl decline
Hemolytic anemia (if G6PD deficient),
methemoglobinemia, leukopenia, N/V,
epigastric pain, hypotension, fever, rash, HA
Boxed Warning: Hematologic: Megaloblastic
anemia, leukopenia, thrombocytopenia, and
pancytopenia most commonly w/ high doses.
Monitor CBC + PLT 2x weekly in patients
receiving high-dose Tx (i.e. toxo)
Other: photosensitive rashes, insomnia,
N/V/D, rash
Rash, fever, crystalluria, anemia,
neutropenia, thrombocytopenia
Infusion related reactions (chills, fever,
hypotension, nausea, rigors)
Dose-related bone marrow suppression
(pancytopenia, leukopenia,
thrombocytopenia)
Others: hepatotoxicity, peripheral
neuropathy, GI intolerance
Contraindicated in patients w/ G6PD
deficiency
Administered w/ leucovorin to
lessen/prevent hematologic
abnormalities
Co-administered w/ Pyrimethamine to
lessen its hematologic toxicities as a
cofactor for thymidylate synthase
Drink 1 – 1.5 liters/day to prevent
drug from crystallizing in urine
(crystalluria)
Contraindicated if hypersensitivity to
sulfonamides or other related drugs
- For chills, fever, hypotension, N –
PREMEDICATE 30-60 min prior to
infusion w/ ibuprofen +/-
diphenhydramine +/-
hydrocortisone
- For rigors, premedicate w/
meperidine
- PRE- and POST-HYDRATE w/ 250-
500 mL NS to reduce
nephrotoxicity
If available, 5-FC levels should be
monitored w/ goal serum levels of 25-
100 mg/dL
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Binds to 50S subunit of
Macrolides bacterial ribosome, thus
(Azithromycin, inhibiting translation of mRNA
Clarithromycin)  interferes w/ protein
synthesis
Inhibits arabinosyl transferase
resulting in impaired
Ethambutol
mycobacterial cell wall
synthesis
Inhibits DNA-dependent RNA
polymerase at beta subunit
Rifabutin
which prevents chain
initiation
Inhibits DNA-gyrase 
Fluoroquinolones
relaxation of supercoiled DNA
(Levofloxacin,
 promotes breakage of DNA
Moxifloxacin)
strands
Binds to 30S ribosomal
Amikacin subunits  inhibits protein
synthesis
Mycobacterium Avium Complex
Azithromycin:
- PPx: 1200 mg PO once weekly
- Tx: 500-600 mg PO/IV once daily
Clarithromycin:
- PPx: 500 mg PO BID
- Tx: 500 mg PO BID
15 mg/kg PO once daily
PPx & Tx: 300 mg once daily
Levofloxacin 500 mg once daily
Moxifloxacin 400 mg once daily
10-15 mg/kg IV daily
N/V, abdominal pain, abnormal taste,
increased LFTs, hypersensitivity rxns, QTc
prolongation (additive)
Optic neuritis  get ophthalmic exams!
Painless blur in vision center
Hyperuricemia (incr. in uric acid)
N/V/D, abdominal pain
Uveitis, red-orange discoloration of fluids,
N/V/D, decreased WBCs and PLTs, Increased
LFTs
Boxed Warnings: Tendonitis/tendon rupture,
peripheral neuropathy, aortic tear risk
increased, hypoglycemia, CNS/mental health
ADE’s
Boxed warnings for ototoxicity (irreversible),
nephrotoxicity
Azithromycin has less DDI’s and has
less probability of ADE’s than
Clarithromycin, but is less effective
At baseline and periodically during
treatment, perform:
- Ophthalmic exams
- LFT’s to evaluate for
hepatotoxicity
Rifabutin is a major substrate of
CYP3A4 and minor substrate of CYP1A2
– DDI’s!
Separate products containing calcium,
magnesium, and iron by 2 hours (i.e.
dairy products, antacids, vitamins)
Ensure that the benefits of adding
amikacin to treatment outweigh the
risks/toxicities