Human Immunodeficiency Virus Book

http://www.fpnotebook.com/

Anti-Retroviral Therapy

Aka: Anti-Retroviral Therapy, HIV Treatment, HIV Medication, Antiretroviral, Anti-retroviral
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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 347:385-94
    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 32:774-82
  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. Preparations
    1. Nucleotide-Nucleoside Reverse Transcriptase Inhibitor (nRTI)
      1. Abacavir (Ziagen, ABC)
      2. Didanosine (Videx EC, ddI)
      3. Emtricitabine (FTC)
      4. Lamivudine (Epivir, 3TC)
      5. Stavudine (Zerit, d4T)
      6. Zalcitabine (Hivid, ddC)
      7. Zidovudine (Retrovir, ZDV or AZT)
      8. Tenofovir (Viread, TDF)
    2. Nonnucleoside Reverse Transcriptase Inhibitor (NNRTI)
      1. Delavirdine (Rescriptor)
      2. Efavirenz (Sustiva, EFV)
      3. Etravirine (Intelence)
      4. Nevirapine (Viramune, NVP)
      5. Rilpivirine (Endurant)
    3. Protease Inhibitor (PI) - suffix '/r' added when combined with Ritonavir
      1. Amprenavir (Agenerase)
      2. Atazanavir (Reyataz, ATV or ATV/r)
      3. Darunavir (DRV or DRV/r)
      4. Fosamprenavir (FPV or FPV/r)
      5. Indinavir (Crixivan)
      6. Lopinavir with Ritonavir (Kaletra, LPV/r)
      7. Nelfinavir (Viracept)
      8. Ritonavir (Norvir, r)
      9. Saquinavir (Fortovase)
      10. Saquinavir mesylate (Invirase)
      11. Tiprinavir (Aptivus)
    4. Entry Inhibitor (Coreceptor Antagonist)
      1. Maraviroc (Selzentry)
    5. Fusion Inhibitor
      1. Enfuvirtide (Fuzeon)
    6. Integrase Strand Transfer Inhibitor (InSTI)
      1. Raltegravir (Isentress, RAL)
  5. Preparations: Combination
    1. Atripla: Efavirenz (EFV), Emtricitabine (FTC) and Tenofovir (TDF)
    2. Combivir: Lamivudine (3TC) and Zidovudine (ZDV)
    3. Epzicom: Abacavir (ABC) and Lamivudine (3TC)
    4. Trizivir: Abacavir (ABC), Lamivudine (3TC), and Zidovudine (ZDV)
    5. Truvada: Emtricitabine (FTC) and Tenofovir (TDF)
  6. Indications: Initiation of Antiretroviral therapy
    1. Panel on Antiretroviral Guidelines
      1. CD4 Count < 350 (<500 per IAS)
      2. Pregnancy
      3. HIV Associated Nephropathy
      4. Hepatitis B coninfection (also for Hepatitis C per IAS )
      5. AIDS Defining Illness
    2. International AIDS Society (IAS) USA Panel
      1. In addition to recommendations above
      2. Symptomatic HIV
      3. Age over 60 years
      4. Cardiovascular disease
      5. High risk for HIV Transmission
      6. Rapid decline in CD4 Count >100/year
      7. Viral load >100,000 copies/ml
  7. Approach: Preferred agents for therapy-naive non-pregnant patients
    1. Based on strong quality data from randomized controlled trials (A-I)
    2. Agent 1: Nucleoside-Nucleotide Reverse Transcriptase Inhibitor (NRTI)
      1. Tenofovir (TDF)
    3. Agent 2: Nucleoside-Nucleotide Reverse Transcriptase Inhibitor (NRTI)
      1. Emtricitabine (FTC)
    4. Agent 3: Choose one
      1. Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI)
        1. Efavirenz (EFV)
          1. Contraindicated in first trimester pregnancy or in women with unreliable Contraception
      2. Protease Inhibitor (PI)
        1. Darunavir with Ritonavir (DRV/r) or
        2. Atazanavir with Ritonavir (ATV/r)
          1. Contraindicated in high dose Proton Pump Inhibitor (e.g. Omeprazole >20 mg daily)
      3. Integrase Strand Transfer Inhibitor (InSTI)
        1. Raltegravir (RAL)
  8. Approach: Preferred agents for therapy-naive pregnant patients
    1. Based on strong quality data from randomized controlled trials (A-I)
    2. Agent 1: Nucleoside-Nucleotide Reverse Transcriptase Inhibitor (NRTI)
      1. Lamivudine (3TC)
    3. Agent 2: Nucleoside-Nucleotide Reverse Transcriptase Inhibitor (NRTI)
      1. Zidovudine (ZDV)
    4. Agent 3: Protease Inhibitor
      1. Lopinavir with Ritonavir (LPV/r)
  9. Approach: Alternative agents for therapy-naive pregnant patients
    1. Based on moderate quality data from randomized controlled trials (A-I)
    2. Agent 1: Nucleoside-Nucleotide Reverse Transcriptase Inhibitor (NRTI)
      1. Lamivudine (3TC)
    3. Agent 2: Nucleoside-Nucleotide Reverse Transcriptase Inhibitor (NRTI)
      1. Zidovudine (ZDV) or
      2. Abacavir (ABC)
        1. Use Zidovudine instead if third agent is Nevirapine (NVP)
        2. Contraindicated in HLA-B*5701 positive patient
        3. Relatively contraindicated if high cardiovascular risk or HIV RNA >100,000 copies/ml pre-treatment
    4. Agent 3: Choose one
      1. Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI)
        1. Efavirenz (EFV)
          1. Contraindicated in first trimester pregnancy or in women with unreliable Contraception
        2. Nevirapine (NVP)
          1. Contraindicated in severe liver disease or pre-Anti-retroviral CD4 >250 in men or >400 in women
      2. Protease Inhibitor (PI)
        1. Atazanavir with Ritonavir (ATV/r)
          1. Contraindicated in high dose Proton Pump Inhibitor (e.g. Omeprazole >20 mg daily)
        2. Fosamprenavir with Ritonavir (FPV/r)
          1. May be used with Tenofovir (TDF) and Emtricitabine (FTC) as first 2 agents
        3. Lopinavir with Ritonavir (LPV/r)
          1. May be used with Tenofovir (TDF) and Emtricitabine (FTC) as first 2 agents
          2. Do not use single daily dosing regimen in pregnancy
  10. 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 33:466-72
  11. 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
  12. 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
  13. Resources
    1. Guidelines for use of Antiretroviral agents in HIV-1 Infected Adults and Adolescents
      1. http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf
      2. Updated 1/10/11 and accessed 10/8/2011
    2. HIV-AIDS Treatment Information Service Website
      1. http://www.hivatis.org
  14. References
    1. (1995) Med Lett Drugs Ther 37: 959
    2. Carpenter (2000) JAMA 283:381-90
    3. Lesho (2003) Am Fam Physician 68(4):675-86
    4. Paterson (2000) Ann Intern Med 133-21-30
    5. Yeni (2002) JAMA 288:222-35

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