2014 IAS-USA Treatment Guidelines

Transcription

1 NORTHWEST AIDS EDUCATION AND TRAINING CENTER 2014 IAS-USA Treatment Guidelines Brian R. Wood, MD Medical Director, NW AETC ECHO Assistant Professor of Medicine, University of Washington Presentation prepared by: Presenter Last Updated: 10/16/14

2 International Antiviral Society-USA Guidelines Updated July 2014 Prevention Guidelines Dr. Marrazzo will discuss 11/6/14 Treatment Guidelines

3 Rating Scale Strength of Recommendations: - A: Strong support - B: Moderate support - C: Limited support Quality of Evidence: - Ia: >1 RCTs published in peer-reviewed literature - Ib: >1 RCTs presented at peer-reviewed scientific meetings - IIa: non-rct s, cohort, or case-control studies published - IIb: non-rct s, cohort, or case-control studies presented - III: panel s analysis of accumulated available evidence

4 When to Start ART is recommended regardless of CD4 count CD4 count <500: AIa CD4 count >500: BIII Pregnancy: AIa Chronic hepatitis B: AIIa HIV-associated nephropathy: AIIa

5 What to Start: Recommended Initial Regimens Anchor Backbone Comments Dolutegravir Tenofovir-emtricitabine May increase serum creatinine Dolutegravir^ Abacavir-lamivudine Abacavir not inferior to tenofovir at high HIV RNA levels if given with dolutegravir Elvitegravir/ cobicistat^ Raltegravir Efavirenz^ Tenofovir-emtricitabine May increase serum creatinine; similar drug interactions as ritonavir Tenofovir-emtricitabine Raltegravir twice daily Tenofovir-emtricitabine CNS/psych SE s; no longer contraindicated in pregnancy but avoid in woman of child-bearing potential Efavirenz Abacavir-lamivudine Same as above Rilpivirine^ Tenofovir-emtricitabine Avoid if HIV RNA >100,000 copies or on PPI; taken with full meal Atazanavir/ritonavir Tenofovir-emtricitabine May cause cholelithiasis/nephrolithiasis; consider H2 blocker/ppi interactions Darunavir/ritonavir Tenofovir-emtricitabine Once-daily dosing for initial therapy ^Single tablet regimen (STR) option!

6 Additional Considerations Tenofovir: - Potential for renal and bone toxicity Abacavir: - Associated with cardiovascular events, though data conflicting - HLA-B*5701 must be negative Abacavir/lamivudine: - Less efficacious than tenofovir/emtricitabine when given with efavirenz or boosted atazanavir if baseline HIV RNA >100,000

7 What to Start: Alternatives Anchor Backbone Comments Raltegravir Abacavir not inferior to tenofovir at high HIV RNA levels if given with raltegravir Nevirapine 2 NRTI s Severe hepatotoxicity may occur if CD4 >250 in women or >400 in men; more severe rash than other NNRTI s Rilpivirine Atazanavir-cobicistat 2 NRTI s Not recommended if HIV RNA >100,000 copies Atazanavir levels equivalent with cobicistat or ritonavir Darunavir-cobicistat 2 NRTI s Darunavir levels equivalent with cobicistat or ritonavir Lopinavir-ritonavir 2 NRTI s May be less tolerable and have increased CV toxicity Darunavir-ritonavir Abacavirlamivudine Abacavirlamivudine Abacavirlamivudine Single randomized study available Darunavir-ritonavir Raltegravir Inferior if CD4 <200 or HIV RNA >100,000 copies Lopinavir-ritonavir Raltegravir Single study available with significant limitations Lopinavir-ritonavir Lamivudine Single study available with significant limitations

8 Estimated Patent Expiration Dates for Branded Antiretrovirals Year Antiretrovirals 2012 Zidovudine, lamivudine, stavudine, didanosine, saquinavir, nevirapine 2013 Ritonavir, efavirenz, zidovudine/lamivudine 2016 Abacavir, lopinavir/ritonavir (softgel) 2017 Tenofovir, atazanavir, darunavir 2019 Etravirine, abacavir/lamivudine 2024 Tenofovir/emtricitabine 2025 Raltegravir 2026 Tenofovir/emtricitabine/efavirenz, tenofovir/emtricitabine/rilpivirine, dolutegravir

9 Initiating ART in Special Circumstances Acute HIV: ART should be offered to all individuals with acute infection and should be started as early as possible to maximize benefit (BIII) Benefits: reduction of proviral DNA and plasma viral load, lower viral set point, robust immune reconstitution Elite Controllers: The data for initiating ART in elite controllers is stronger than before but still insufficient to recommend routine therapy

10 Initiating in Setting of an Acute OI or Tuberculosis Acute OI: Start within first 2 weeks of diagnosis (AIa) Includes other AIDS-defining illnesses likely lymphoma or HPV-related cancer (AIa-BIII) Timing less certain for crypto meningitis (COAT trial) Tuberculosis: Within 2 weeks if CD4 count <50 (AIa) By 8-12 weeks if higher CD4 count (AIa) TB meningitis: optimal timing less certain, but likely should be started within 2-8 weeks (BIII)

11 ART Monitoring HIV RNA 4 weeks after ART initiation or change, then every 3 mo (AIa) Evaluate for cause of virological failure if HIV RNA >200 copies (AIIa) CD4 Once HIV RNA suppressed for >2 years and CD4 consistently >500, monitoring CD4 count is optional (CIII) There are insufficient data to make general recommendations for the management of patients with sustained viremia of 50 to 200 copies/ml.!