Human Immunodeficiency Virus Book

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HIV Treatment StrategyAka: HIV Medication, Antiretroviral

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  1. Management: Anti-Retroviral Resistance Testing
    1. Goal: Identify HIV strain type to develop regimen
    2. Reasoning
      1. HIV drug resistance is common even at HIV onset
        1. Little (2002) N Engl J Med 347:385
    3. Indications
      1. HIV patients failing therapy
      2. Consider on establishing initial therapy
    4. Testing
      1. Genotypic Antiretroviral Resistance Testing (GART)
      2. Phenotypic Antiretroviral Resistance Testing (PART)
    5. References
      1. Hanna (2001) Clin Infect Dis 32:774
  2. Pearls: Compliance is critical to suppress viral load (<500 c/ml)
    1. Adherence of 95% to drug regimen: 81% success rate
    2. Adherence of 90-95% to drug regimen: 64% success rate
    3. Adherence of 80-90% to drug regimen: 50% success rate
    4. Adherence of 70-80% to drug regimen: 24% success rate
    5. Adherence of <70% to drug regimen: 6% success rate
  3. Pearls: better compliance
    1. Compliance is critical to prevent drug resistance
      1. Set up reminders to take medications
        1. Alarm clock
        2. Pill box
        3. Place medication on night stand
      2. Anticipatory guidance that adverse effects are common
    2. Patient forgets to take dose
      1. Take dose as soon as remembered
      2. Take next dose if time (do not double dose)
    3. Patient experiences adverse effects
      1. Call primary doctor or pharmacist
      2. Do not stop just one anti-Retroviral medication
        1. Stop all anti-Retrovirals, or stop none
        2. Prevents developing resistance to Antiretrovirals
    4. Patient traveling
      1. Gradually adjust dosing to the next time zone
      2. Ritonavir may be un-refrigerated for 30 days
    5. Understand that cost is very expensive: $1000/month
    6. Consider combination pills that reduce number per day
      1. Combivir (AZT/3TC) bid with Efavirenz qhs (*)
      2. Trizavir (AZT/3TC/Abacavir) 1 po bid
  4. Agents
    1. Nucleoside Reverse Transcriptase Inhibitor (nRTI)
      1. Abacavir (Ziagen)
      2. Didanosine (Videx, ddI)
      3. Lamivudine (Epivir, 3TC)
      4. Stavudine (Zerit, d4T)
      5. Zalcitabine (Hivid, ddC)
      6. Zidovudine (Retrovir, ZDV or AZT)
      7. Abacavir, Lamivudine, and Zidovudine (Trizivir)
      8. Lamivudine and Zidovudine (Combivir)
    2. Nucleotide Reverse Transcriptase Inhibitor (NtRTI)
      1. Tenofovir (Viread)
    3. NonNucleoside Reverse Transcriptase Inhibitor (NNRTI)
      1. Delavirdine (Rescriptor)
      2. Efavirenz (Sustiva)
      3. Nevirapine (Viramune)
    4. Protease Inhibitor (PI)
      1. Amprenavir (Agenerase)
      2. Atazanavir (Reyataz)
      3. Indinavir (Crixivan)
      4. Lopinavir with Ritonavir (Kaletra)
      5. Nelfinavir (Viracept)
      6. Ritonavir (Norvir)
      7. Saquinavir (Fortovase)
      8. Saquinavir mesylate (Invirase)
    5. Fusion (Inhibitor)
      1. Enfuvirtide (Fuzeon)
  5. Initial Approach
    1. Note: Most regimens involve 3 or more drugs
    2. CD4 Count > 350-500 Cells and HIV Viral Load <5,000
      1. Consider observation
    3. CD4 Count > 200 Cells
      1. HIV Viral Load <5000
        1. Double nRTI therapy and third agent
      2. HIV Viral Load 5000 - 20,000
        1. Double nRTI therapy and third agent
      3. HIV Viral Load 20,000 - 100,000
        1. Double nRTI therapy and NNRTI
      4. HIV Viral Load >100,000
        1. Double nRTI therapy and Protease Inhibitor
    4. CD4 < 200 Cells
      1. HIV Viral Load <20,000
        1. Double nRTI therapy and NNRTI or Protease Inhibitor
      2. HIV Viral Load 20,000 - 100,000
        1. Double nRTI therapy and Protease Inhibitor
      3. HIV Viral Load >100,000
        1. nRTI PLUS double Protease Inhibitor OR
        2. Double nRTI therapy and Protease Inhibitor
  6. Monitoring: Viral Load 3 Months after starting therapy
    1. Failure to decrease viral load by 0.5 log copies/ml
      1. Address compliance (see above)
      2. Consider change in therapy
    2. Predictors of decreased HIV progression
      1. Viral load decreases by >0.5 log copies/ml
      2. CD4 Count increases >200 cells/mm3
    3. Reference
      1. Kitchen (2001) Clin Infect Dis 33:466
  7. Efficacy: Retroviral therapy payoff is excellent
    1. Dollars denote cost per life saved
    2. Antiretroviral therapy: $10,000 to $18,000
    3. HMG CoA Reductase Inhibitors: $21,000
    4. Mammogram: $30,000
    5. Flexible Sigmoidoscopy and FOBT: $43,000
    6. Hemodialysis: $50,000
    7. Warfarin for Atrial Fibrillation: $110,000
    8. Prostate Cancer Screening: $113,000
    9. Coronary Artery Bypass Graft: $113,000
  8. Drug Interactions
    1. Antiretroviral drug interactions are common
    2. Interactions often lower Antiretroviral concentrations
    3. Drug interactions frequently cause viral resistance
    4. Address potential interactions when starting new agent
  9. Resources
    1. HIV-AIDS Treatment Information Service Website
      1. http://www.hivatis.org
  10. References
    1. (1995) Med Lett Drugs Ther 37:959
    2. Carpenter (2000) JAMA 283:381
    3. Lesho (2003) Am Fam Physician 68(4):675
    4. Paterson (2000) Ann Intern Med :
    5. Yeni (2002) JAMA 288:222

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