VIRTUAL MEDZONEYour Resource for HIV Related Innovative Medical Communication

HIV CASE PRESENTATIONSAlice Tseng Pharm.D., FCSHP, AAHIVPDavid Fletcher MD FRCPC

CASE 1• 54 yo Caucasian woman, Dx HIV & HCV

in 2002 • ARV treatment (CD4 280, VL 40,526)

DATE ARV REGIMEN VL CD410/02 AZT/3TC/NFV <50 47710/07 AZT/3TC/LPVr <50 72709/09 TDF/FTC/LPVr <50 819

CASE 1HCV 1a (gr 3-4 fibrosis, RNA 1.32E+6

IU/mL)DATE TREATMENT OUTCOME02/03 RBV+peg-IFN d/c after 2 doses

(↓Hgb, ANC)06/03 Amitriptyline,

RBV+peg-IFN, EPO, GCSF

d/c after 2 weeks

09/05 LFTs still pre-RBV, peg-IFN 2A

d/c after wk 12 (supoptimal response)

CASE 1Considerations with HCV protease inhibitors:• Telaprevir:• LPVr: 54% AUC, 52% Cmin of TVR• DRVr: 35% AUC, 32% Cmin of TVR; also 40%

AUC, 42% Cmin of darunavir• ATVr: 20% AUC, 15% Cmin of TVR; least impact

of all current PIs ongoing evaluation in HIV/HCV• Tenofovir: AUC (relevance?). Monitor Scr.

• Boceprevir:• minimal effects of RTV 100 mg QD and BID on

BOC AUC

CASE 1So how should we manage this patient on TDF /FTC/LPVr?...switch ARVs

Telaprevir• RTV/ATZ• EFV• RaltegravirBoceprevir…stay tuned

CASE 2• 50 yo, Caucasian male, • HIV+ since 1992• VL suppressed since 1996, CD4 720• some NRTI mutations, no PI mutations,

R5+• on 3TC, SQV 600/RTV 300 mg BID, RAL

BID since 2008

CASE 2Asthma: prev. on Symbicort (budesonide/formoterol) inhaler• interaction with RTV/SAQ adrenal

suppression/ insufficiency, Cushings Syndrome (2010)

• also has osteoporosis, hyperlipidemia, autoimmune retinopathy

How do you manage his asthma?

CASE 3• 62 yo male, HIV+ 1992• extensive ARV history with AEs &

resistance• CAD, CHF, HTN, hyperlipidemia,

NIDDM, gout, chronic renal insufficiency

CASE 3Meds:• ABC, 3TC, LPVr, T20• TMP/SMX DS, allopurinol, metoprolol,

furosemide, Aggrenox (dipyridamole 200 mg/ASA 25 mg), amlodipine, rosuvastatin

• Dx pulmonary arterial hypertension (PAH) 2003, respirologist Rx bosentan…

How do you manage this patient?

PAH THERAPIES

Substrate P450

Substrate (other)

Inducer/ Inhibitor

Endothelin Receptor Antagonists:

Bosentan (Tracleer®) 3A4, 2C9 2C9, 3A4 (inducer)

Ambrisentan (Volibris®)

CYP3A4, 2C19

UGT1A9S, 2B7S, 1A3S, Pgp

Phosphodiesterase inhibitors:

Sildenafil (Revatio®) 3A4>>2C9

1A2, 2C9, 2C19, 2D6, 2E1, 3A4 (weak inhibitor)

Tadalafil (Adcirca®) 3A4

POTENTIAL INTERACTION BETWEEN BOSENTAN & PIS

• Possibility of bosentan and/or lopinavir/r concentrations via CYP450 inhibition/induction

• Usual bosentan dose:• 62.5 mg BID x 4 weeks, then 125 mg BID

POTENTIAL INTERACTION BETWEEN BOSENTAN & PIS

• May 2004: Rx bosentan 62.5 mg BID, LPV/r to 5 capsules BID

• 1 month later developed recurrent anemia requiring transfusions despite iron supplementation & EPO

POTENTIAL INTERACTION BETWEEN BOSENTAN & PIS• anemia associated with bosentan is

dose-related• in controlled studies, Hgb of at least

10 g/L observed in 57% bosentan-tx subjects vs. 29% placebo group

ADMINISTERING BOSENTAN WITH PROTEASE INHIBITORSManagement:• if already on stable PI tx: initiate bosentan

62.5 mg q1-2days• if on stable bosentan and require PI: d/c

bosentan for >36 h, start PI x 10 days, re-start bosentan at 62.5 mg q1-2days

[DHHS Guidelines, Oct 14/11; Tracleer monograph, June 2011; Reyataz monograph, May 2011.]

ADMINISTERING BOSENTAN WITH PROTEASE INHIBITORSMonitoring parameters:• efficacy: improvement in exercise

tolerance, NYHA functional status severity and hemodynamic measures via right heart catheterization. Also suggest PI TDM & VL.

[DHHS Guidelines, Oct 14/11; Tracleer monograph, June 2011; Reyataz monograph, May 2011.]

ADMINISTERING BOSENTAN WITH PROTEASE INHIBITORSMonitoring parameters:• toxicity: headache, flushing, GI effects,

anemia, liver injury, worsening CHF (wt gain, leg edema) and pulmonary edema (SOB, painful/difficult breathing)

• Atazanavir: do not use unboosted atazanavir with bosentan (may ATV)

[DHHS Guidelines, Oct 14/11; Tracleer monograph, June 2011; Reyataz monograph, May 2011.]

CASE 4• 66 yo male, HIV+ 1992• NIDDM, hyperlipidemia, HTN,

renal dysfunction (multifactorial), peripheral neuropathy, depression, BPH, chronic pain

CASE 4Medications• DRV/r BID, RAL BID, ETV BID• ASA, amlodipine, ramipril, coenzyme Q10,

fenofibrate, ezetimibe, atorvastatin, metformin, Prandase (acarbose), Januvia (sitagliptin), Cymbalta (duloxetine), ACV, Detrol (tolterodine), dulcolax, colace, metamucil, Flonase prn, testosterone cream

• Urologist wants to add daily tadalafil:Interaction with DRV/r?

IMPACT OF PIS ON PDE5 INHIBITORS

Sildenafil

Tadalafil Vardenafil

Darunavir/r 300% Fosamprenavir/r

Priapism (case)

Lopinavir/r 100% Ritonavir 1000%

(500mg BID)

124% (200 mg BID)

49-fold (600 mg BID)

Saquinavir/r 210%

DOSING OF PDE5 INHIBITORS WITH PIS

*if on stable tadalafil and starting PI therapy: d/c tadalafil for at least 24 h, start PI, restart tadalafil after 7 days at 20 mg QD with to 40 mg QD prn

For PAH Sildenafil Tadalafil VardenafilUsual Dose 20 mg TID 40 mg QDWith PI/r Contraindicate

d20mg QD, to 40 mg QD if tolerated

For ED Sildenafil Tadalafil VardenafilUsual Dose 50-100 mg QD 10-20 mg QD

prn2.5-5 mg OD (daily dosing)

With PI/r 25 mg q48h 10 mg q48h, max 3x/wk

No change

NB: Vardenafil is contraindicated with ritonavir, indinavir, ketoconazole and itraconazole