PowerPoint Presentation - Florida AIDS Education and Training

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					Resistance Testing Case
        Studies
  Joanne J. Orrick, Pharm.D., BCPS
              Clinical Assistant Professor
                  University of Florida
                         Faculty
 Florida/Caribbean AIDS Education and Training Center
                     Gainesville, FL
       Disclosure of Financial Relationships
This speaker has the following significant financial relationships
             with commercial entities to disclose:

 • Boeringer-Ingelheim (Speaker’s Bureau)




This slide set has been peer-reviewed to ensure that there are no conflicts of
                   interest represented in the presentation.
             Case Study TP
• TP is a 37 year old black male who has been
  known to be HIV positive since Dec. 2000 and has
  been on multiple ARV regimens.
• PMH: chronic hepatitis C (genotype 3a, VL > 10
  million) with intermittently increased LFTs (most
  recent WNL), recurrent genital HSV, and
  polysubstance abuse, HIV wasting, AIDS
  encephalopathy
• Current medications: Septra DS® 1 po qd,
  acyclovir 400 mg po bid
           Case Study TP
• CD4 231 (8%), VL 424,601 (October 2006)
• Nadir CD4 count <20 cells/mm3
• Resistance testing performed October
  2006 when patient on an ARV regimen of
  tenofovir (Viread®) 300 mg qd, didanosine
  EC (Videx EC®) 250 mg qd, atazanavir
  (Reyataz®) 300 mg qd, ritonavir (Norvir®)
  100 mg qd
TP: VircoType
TP: VircoType
             Case Study TP
• What additional information do you need prior to
  making a recommendation for a new regimen?
  • Adherence to ARVs and commitment to take
    ARVs?
  • Is patient a candidate for T-20 (Fuzeon®)?
  • Past ARVs?
  • Renal function, liver function, CBC, lipids?
  • Prior resistance testing results?
  • Are expanded access medications available?
           Case Study TP
• Patient has a history of polysubstance
  abuse (reports currently not using) and
  nonadherence to ARV regimens
• Patient is not interested in taking
  injections (i.e. T-20)
            Case Study TP
• Past ARVs: stavudine (Zerit®), abacavir
  (Ziagen®), lamivudine (Epivir®),
  didanosine (VIdex EC®), tenofovir
  (Viread®), efavirenz (Sustiva®), atazanavir
  (Reyataz®), ritonavir (Norvir®), nelfinavir
  (Viracept®)
• Patient did not discontinue any ARVs due
  to adverse effects
                        CD4/VL Trends-Case TP
800                                                                                                                        500000
                                                       CD4
700
                                                       Viral Load                                                        424601
                                                                                                                            400000
600

500
                                                                                                                           300000
400

300                                                             198750                                                     200000
                                   178,099
                                        265          169331 263     280                               272          280
                154000                                   255                                                 246
                                               212                                            216                        231
200
                                                     147                       163                                         100000
                                                                                                                   82600
100                                107                                                        66230
                        70
                                                                                                             27000
                15                             12775        5110 75                                   5580
     0                  400              400                                           618                                 0
         0

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            Case Study TP
• Mutations identified on past resistance
  tests: (prior tests on 5/31/06, 10/4/02,
  8/13/03
   • NRTI mutations: 41M/L, E44E/D, T215Y,
     184V, 74V, 70E, 115F, 211K, 115F
   • NNRTI mutations: 188C, 103T, 106I
   • PI mutations: 71T, 30N, 54I/L, 10F, L63P,
     K20K/T, E35E/G, V77I, N88D
TP: Stanford DB Interpretation




                  http://hivdb.stanford.edu/
TP: Stanford DB Interpretation




                 http://hivdb.stanford.edu/
            Case Study TP-
         NRTI Backbone Options
•   Truvada® (emtricitabine 200mg/tenofovir 300 mg) 1 po qd +
    zidovudine 300 mg po bid (patient has resistance to 3TC which
    may partially reverse resistance to AZT, intermediate tenofovir
    resistance)
•   Combivir® (zidovudine 300 mg + lamivudine 150 mg) 1 po bid +
    Viread® (tenofovir) 300 mg po qd (would provide similar
    coverage as above option)
•   Trizivir® (zidovudine 300 mg + lamivudine 150 mg + abacavir
    300 mg) 1 po bid + Viread® (tenofovir) 300 mg po qd (similar
    rationale as above; patient shows resistance to abacavir so
    Trizivir® will provide uncertain benefit over Combivir; however,
    patient has extensive resistance mutations and does not have
    full susceptibility to any NRTI so it may be worth considering
    this backbone).
•   Ziagen® (abacavir) 600 mg po qd + Emtriva® (emtricitabine) 200
    mg po qd + zidovudine 300 mg po bid
Case Study TP-NNRTI Options
• Most recent resistance test shows susceptibility
  to NNRTIs; however, patient has past evidence of
  high level resistance so would not include NNRTI
  in next regimen.
• Second generation NNRTIs should be available in
  the future (TMC 125 available via expanded
  access) and we would want to prevent further
  NNRTI resistance which might impact
  susceptibility to these 2nd generation NNRTIs.
                PI Options
•   Kaletra® (lopinavir/ritonavir)-higher dose
    (3 tabs po bid) due to low-level
    resistance
•   Lexiva® (fosamprenavir) 700 mg po bid +
    Norvir® (ritonavir) 100 mg po bid
•   Prezista® (darunavir) 600 mg po bid +
    Norvir® (ritonavir ) 100 mg po bid
•   Invirase® (saquinavir) 1000 mg po bid +
    Norvir (ritonavir) 100 mg po bid
           Case Study WY
• WY is a 43 year old male who has been
  HIV positive since 1995.
• He has multiple drug allergies: sulfa,
  penicillin, erythromycin, tetracycline,
  trovofloxacin, ciprofloxacin, clindamycin,
  amprenavir, efavirenz, nevirapine
• Although he has been adherent, he has
  expressed concern with the pill burden of
  his current ARV regimen
            Case Study WY
• PMH: CMV retinitis (1998, now resolved
  but legally blind in right eye), neuropathy,
  chronic diarrhea, leukopenia,
  hypothyroidism, hyperlipidemia, GERD,
  lipodystrophy, Type 2 DM, seborrheic
  dermatitis
           Case Study WY
• Current Medications:
• ARVs: Rescriptor® (delavirdine) 400 mg
  po tid, Epivir ® (lamivudine) 150 mg po bid,
  Crixivan® (indinavir) 800 mg po bid,
  Norvir® (ritonavir) 100 mg po bid
• Others: Synthroid® (levothyroxine)
  150 mcg po qd, Prevacid® (lansoprazole)
  30 mg po qd, Lipitor® (atorvastatin) 10 mg
  po qd, Glucophage® (Metformin) 500 mg
  po bid, Lopid ® (gemfibrizol) 600 mg po bid
                                         CD4/VL Trends
800                                                                                                                 80000
                                                     CD4
700                         69766                                                                                    70000
                                                     Viral Load                669                                662
                                                                                                     647
600                                                                                                                 60000
                                                                                              575
                                                                      542              554                  536
500                                                                                                                 50000
                                                            473
400                                                                                                                 40000
                   35000                            350
300                                         316                                                                     30000
                                    273
200                                                                                    19092                        20000
                            125
100                                                                                                                 10000
                                                                                              5744
          29       35                                                                                1430 1108 2228
  0                                 497 499 88              364 49             49                                 0
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WY: Genotype
WY: Stanford DB Interpretation




            http://hivdb.stanford.edu/
WY: Stanford DB Interpretation




                 http://hivdb.stanford.edu/
           Case Study WY
• Past ARVs: Retrovir® (zidovudine), Hivid®
  (zalcitabine), Fortovase® (saquinavir),
  Ziagen® (abacavir), Zerit® (stavudine)
           Case Study WY
• What modifications (if any) would you
  make to the patient’s ARV regimen?
   Case Study WY: Follow Up
• Patient placed on regimen of Truvada ® 1
  po qd + Kaletra® (lopinavir/ritonavir) 3 tabs
  (600/150 mg) po bid in May 2006
• Subsequent CD4 and Viral load counts
   • 6/06: VL < 75, CD4 517
   • 8/06: VL < 75, CD4 558
   • 1/07: VL < 75, CD4 542

				
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posted:9/5/2011
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