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SYNCing Guidelines- Catanzaro
SYNCing Guidelines- Catanzaro
SYNCing Guidelines- Catanzaro
SYNCing Guidelines- Catanzaro
SYNCing Guidelines- Catanzaro
SYNCing Guidelines- Catanzaro
SYNCing Guidelines- Catanzaro
SYNCing Guidelines- Catanzaro
SYNCing Guidelines- Catanzaro
SYNCing Guidelines- Catanzaro
SYNCing Guidelines- Catanzaro
SYNCing Guidelines- Catanzaro
SYNCing Guidelines- Catanzaro
SYNCing Guidelines- Catanzaro
SYNCing Guidelines- Catanzaro
SYNCing Guidelines- Catanzaro
SYNCing Guidelines- Catanzaro
SYNCing Guidelines- Catanzaro
SYNCing Guidelines- Catanzaro
SYNCing Guidelines- Catanzaro
SYNCing Guidelines- Catanzaro
SYNCing Guidelines- Catanzaro
SYNCing Guidelines- Catanzaro
SYNCing Guidelines- Catanzaro
SYNCing Guidelines- Catanzaro
SYNCing Guidelines- Catanzaro
SYNCing Guidelines- Catanzaro
SYNCing Guidelines- Catanzaro
SYNCing Guidelines- Catanzaro
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SYNCing Guidelines- Catanzaro

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  • Summary of Recommended Regimens The most extensively studied combination antiretroviral regimens for treatment-naïve patients generally consist of two NRTIs plus either one NNRTI or a PI (with or without ritonavir boosting). A list of Panel-recommended components for initial therapy in treatment-naïve patients can be found in Table 6 . Potential advantages and disadvantages of the components recommended as initial therapy for treatment-naïve patients are listed in Table 7 to guide prescribers in choosing the regimen best suited for an individual patient. A list of agents or components not recommended for initial treatment can be found in Table 8 . Some agents or components that are not recommended for use because of lack of potency or potential serious safety concerns are listed in Table 9
  • Transcript

    • 1. Guideline Summary:When to Start ART Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Andy Catanzaro, MD Infectious Diseases acatanzaro@unityhealthcare.org March 2012
    • 2. Outline  Overview of HIV therapy  Initiation of Therapy  Special Issues2 October 2011 www.aidsetc.org
    • 3. HIV Terms/Acronyms TermsART: Antiretroviral TherapyHIV Viral Load: amount of virus in the bloodUndetectable Viral Load: Goal of TherapyCD4 Count: Immune MarkerGenotype: Sensitivity of the Virus to Medications3 October 2011 www.aidsetc.org
    • 4. Goal of HIV Therapy: Stop the Virus!
    • 5. What are ‘The Guidelines’ for HIV TherapyIndependent panel of expertsReview Current Literature on HIVMake RecommendationsStrength of Evidence given for each guidance (www.aidsinfo.nih.gov) October 2011 www.aidsetc.org
    • 6. What the Guidelines Address  Baseline evaluation  Laboratory testing  When to initiate & change therapy  Therapeutic options  ART-associated adverse effects6
    • 7. What the Guidelines Address  Treatment of acute HIV infection  Special considerations (pregnant, injection drug users, coinfected with HBV, HCV, or TB)  Preventing secondary transmission7
    • 8. Websites to Access the Guidelines  http://aidsinfo.nih.gov  http://www.aidsetc.org8
    • 9. Goals of Treatment Improve quality of life Reduce HIV-related morbidity and mortality Restore and/or preserve immunologic function Suppress HIV viral load Prevent HIV transmission9
    • 10. Use of CD4 Cell Levels to Guide Therapy Decisions CD4 count  The major indicator of immune function  Most recent CD4 count is best predictor of disease progression  A key factor in decision to start prophylaxis  Important in determining response to ART  Adequate response: CD4 increase 50-150 cells/µL per year *10
    • 11. Studies in patients CD4>500 Favor Treatment  Neutral on Treatment  NA-ACCORD  ART-CC  CASCADE11
    • 12. ART in Treatment Recommended forAll PatientsCD4 count Strength of the Evidence for the Recommendation Recommendation<350 Strong Data from randomized clinical trials350-500 Strong Data from non-randomized clinical trials>500 Moderate Expert Opinion12
    • 13. Use of HIV RNA Levels to Guide Therapy Decisions  HIV RNA  May influence choice of ART  Critical in monitoring response to ART  Goal of ART: HIV RNA below limit of detection (ie, <20-75 copies/mL, depending on assay)13
    • 14. Use of HIV RNA Levels to Guide Therapy Decisions (2)  RNA monitoring  Check at baseline  Before initiating ART  2-4 weeks (not more than 8 weeks) after start or change of ART, then every 4-8 weeks until suppressed to <200 copies/mL  Every 3-4 months with stable patients; may consider every 6 months for stable adherent patients with VL suppression >2-3 years  Isolated “blips” may occur (transient low-level RNA, typically <400 copies/mL), are not thought to predict virologic failure  ACTG defines virologic failure as confirmed HIV RNA >200 copies/ mL14
    • 15. When to Start ART Potent ART may improve and preserve immune function in most patients with virologic suppression, regardless of baseline CD4 count  ART indicated for all with low CD4 count or symptoms  Earlier ART may result in better immunologic responses and better clinical outcomes  Reduction in AIDS- and non-AIDS-associated morbidity and mortality  Reduction in HIV-associated inflammation and associated complications  Reduction in HIV transmission  Recommended ARV combinations are considered to be durable and tolerable15
    • 16. When to Start ART Exact CD4 count at which to initiate therapy not known, but evidence points to starting at higher counts Current recommendation: ART for all patients with CD4  Randomized control trial (RTC) data support benefit of ART if CD4 count ≤350 cells/µL  No RTC data on benefit of ART at CD4 counts of >350 cells/µL, but observational cohort data exist Currently available ARVs are effective and well tolerated16
    • 17. Potential Benefits of Early Therapy (CD4 count >500 cells/µL) Cohort study data show survival benefit if ART initiated at CD4 count >500 cells/µL Earlier ART may prevent HIV-related end organ damage; deferred ART may not reliably repair damage acquired earlier  Increasing evidence of direct HIV effects on various end organs and indirect effects via HIV-associated inflammation  End organ damage occurs at all stages of infection17
    • 18. Potential Benefits of Early Therapy (CD4 count >500 cells/µL) (2) Potential decrease in risk of many complications, including:  HIV-associated nephropathy  Liver disease progression from hepatitis B or hepatitis C  Cardiovascular disease  Malignancies (AIDS defining and non-AIDS defining)  Neurocognitive decline  Blunted immunological response owing to ART initiation at older age  Persistent T-cell activation and inflammation18
    • 19. Potential Benefits of Early Therapy (CD4 count >500 cells/µL) (3) Prevention of sexual and blood borne transmission of HIV Prevention of mother-to-child transmission of HIV Prevention of transmission to a sexual partner19
    • 20. Potential Limitations of Early Therapy (CD4 count >500 cells/µL)  ARV-related toxicities  Drug resistance  Non-adherence to ART  Cost20
    • 21. Recommendations for Initiating ART (3) Patients may choose to postpone ART Providers may elect to defer ART, based on patients’ clinical or psychosocial factors  caveat: do we really know who is ready?21
    • 22. Consider More Rapid Initiation of ART(e.g. before the genotype is available) Pregnancy Acute opportunistic infection Lower CD4 count (eg, <200 cells/µL) Rapid decline in CD4 Higher viral load HIV Associated Nephropathy HBV coinfection when HBV treatment is indicated22
    • 23. Consider Deferral of ART Clinical or personal factors may support deferral of ART  If CD4 count is low, deferral should be considered only in unusual situations, and with close follow-up When there are significant barriers to adherence If comorbidities complicate or prohibit ART “Elite controllers” and long-term nonprogressors23
    • 24. Initial ART Regimens: DHHS Categories Preferred  Randomized controlled trials show optimal efficacy and durability  Favorable tolerability and toxicity profiles24
    • 25. Initial Treatment: Choosing Regimens  3 main categories:  1 Non-nucleoside Reductase Inhibitor + 2 Nucleside Reductase Inhibitor (NRTI)  1 Protease Inhibitor + 2 NRTIs  1 Integrase Inhibitor + 2 NRTIs  Combinations preferred for most patients  (Bias: Once Daily Preferred by patients)25
    • 26. Initial Therapy: Fixed Dose CombinationsPreferred:  Once-daily dosing  High virologic efficacyTDF/FTC  Active against HBV(Truvada)  Potential for renal toxicityAlternative:  Once-daily dosing  Risk of hypersensitivity reaction if positive forABC/3TC HLA-B*5701(Epzicom)  Possible inferior efficacy if baseline HIV RNA >100,000 copies/mL  Active against HBVAcceptable:  Twice-daily dosing  Preferred for pregnant womenZDV/3TC  More toxicities than TDF/FTC or ABC/3TC(Combivir)26
    • 27. Initial Regimens: PreferredNNRTI based EFV/TDF/FTC (Atripla) 1,Protease ATV/r (Reyataz/Norvir) + TDF/Inhibitor FTC (Truvada) based DRV/r (Prezista/Norvir) + TDF/ FTC (Truvada)²Integrase RAL (Isentress BID) +Inhibitor based TDF/FTC (Truvada)Pregnant women LPV/r (Kaletra BID) + ZDV/3TC (Combivir)² 1. EFV should not be used during the first trimester of pregnancy or in women trying to conceive or not using effective and consistent27 contraception.
    • 28. Drug-Drug InteractionsToo CommonAlways check new medicationsResources: Guidelines, Uptodate, Epocrates October 2011 www.aidsetc.org
    • 29. Websites to Access the Guidelines  http://www.aidsetc.org  http://aidsinfo.nih.gov29

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