Presentation on theme: "2014: HIV, HCV, and HBV Update David Spach, MD Professor of Medicine, Division of Infectious Diseases University of Washington Last Updated: June 12,"— Presentation transcript:
1 2014: HIV, HCV, and HBV UpdateDavid Spach, MD Professor of Medicine, Division of Infectious Diseases University of WashingtonLast Updated: June 12, 2013
2 Chronic Viral Diseases and Mortality in United States Which one of the chronic viral diseases was responsible for the most number of deaths in the United States in 2007? A. Hepatitis A virus B. Hepatitis B virus C. Hepatitis C virus D. HIV
3 Age-Adjusted Mortality Rates from HBV, HCV, & HIV United States, 1999-2007 654Hepatitis CRate per 100,000 PY32Hepatitis B1199920002001200220032004200520062007YearSource: Ly KN, et al. Ann Intern Med. 2012:156:271-8.
4 Forecasted Annual HCV-Related Deaths in the United States Persons with Chronic Hepatitis C and no Cirrhosis in 2005NumberYear2010Deaths20142018202220262030203420382042204620502054205840,00035,00030,00025,00020,00015,00010,0005,00045,000PeakSource: Rein DR, et al. Dig Liver Dis. 2011:43:66-72.
16 Sofosbuvir + PEG + RBV: Treatment-Naive HCV GT 1,4,5,6 NEUTRINO Trial: Design Week1224Sofosbuvir + PEG + RBVN =327SVR12Drug Dosing Sofosbuvir: 400 mg once daily Peginterferon alfa-2a: 180 µg once weekly Ribavirin (weight-based and in 2 divided doses): 1000 mg/day if < 75 kg or 1200 mg/day if ≥ 75 kgSource: Lawitz E, et al. N Engl J Med ;368:
17 NUTRINO: SVR 12 by Genotype Sofosbuvir + PEG + RBV: Treatment-Naive HCV GT 1,4,5,6 NEUTRINO Trial: ResultsNUTRINO: SVR 12 by Genotype261/292206/22554/6634/35GT = genotypeSource: Lawitz E, et al. N Engl J Med ;368:
18 Hepatitis C TreatmentAccording to 2014 AASLD/IDSA/IAS-USA guidance, which on of the following regimens is recommended for initial treatment of patients with genotype 1 chronic HCV? Assume the patient is eligible to receive interferon A. Peginterferon + Ribavirin + Telaprevir x 12 weeks B. Peginterferon + Ribavirin + Sofosbuvir x 12 weeks C. Peginterferon + Ribavirin + Sofosbuvir x 12 weeks D. Sofosbuvir + Simeprevir x 24 weeks
19 AASLD/IDSA/IAS-USA 2014 HCV Treatment Recommendations Initial Recommended Therapy for Patients with Chronic HCVHCV: Recommended Initial Treatment & Retreatment of Relapsers*GT1Interferon EligibleSofosbuvir + Peginterferon + Ribavirin x 12 weeksNot Interferon EligibleSofosbuvir + Simeprevir +/- Ribavirin x 12 weeksGT2Sofosbuvir + Ribavirin x 12 weeksGT3Sofosbuvir + Ribavirin x 24 weeksGT4Interferon Eligible Sofosbuvir + Peginterferon + Ribavirin x 12 weeks*Patients who experienced relapse after Peginterferon plus Ribavirin therapySource: AASLD/IDSA/IAS-USA (www.hcvguidelines.org).
20 Hepatitis C Genotype 1 Costs of Different Regimens for Treatment of Genotype 1 Estimated Medication Cost for Treatment of Genotype 1 Chronic HCVRegimen and DurationRegimen CostSofosbuvir + Ribavirin + Peginterferon x 12 weeks$97,000Sofosbuvir x 12 weeks + [Ribavirin + Peginterferon] x 24 weeks$109,000Sofosbuvir + Ribavirin x 24 weeks$169,000Sofosbuvir + Simeprevir +/- Ribavirin x 12 weeks$150,000Simeprevir x 12 weeks + [Ribavirin + Peginterferon] x 24 weeks$79,000Simeprevir x 12 weeks + [Ribavirin + Peginterferon] x 48 weeks$104,000Note: sofosbuvir cost = $1000 per day of treatment
21 INVESTIGATIONALLedipasvir-Sofosbuvir +/- Ribavirin in Treatment-Naïve HCV GT 1 ION-1 Study: Study DesignWeek122436GT-1 Naiven = 214LDV-SOFSVR12n = 217LDV-SOF + RBVSVR12GT-1 Naiven = 217LDV-SOFSVR12n = 217LDV-SOF + RBVSVR12Drug Dosing Ledipasvir-sofosbuvir (90/400 mg): fixed dose combination; one pill once daily Ribavirin (weight-based and divided bid): 1000 mg/day if < 75 kg or 1200 mg/day if ≥ 75 kgN =14Abbreviations: LDV= ledipasvir; SOF = sofosbuvir; RBV = ribavirinSource: Afdhal N, et al. N Engl J Med. 2014;370:
22 ION-1: SVR 12 by Treatment Duration and Regimen INVESTIGATIONALLedipasvir-Sofosbuvir +/- Ribavirin in Treatment-Naïve HCV GT 1 ION-1 Study: ResultsION-1: SVR 12 by Treatment Duration and Regimen211/214211/217212/217215/21712-Week Regimen24-Week RegimenLDV= ledipasvir; SOF = sofosbuvir; RBV = ribavirinSource: Afdhal N, et al. N Engl J Med. 2014;370:
23 ION-1: SVR12 by Treatment Regimen and Liver Disease INVESTIGATIONALLedipasvir-Sofosbuvir +/- Ribavirin in Treatment-Naïve HCV GT 1 ION-1 Study: ResultsION-1: SVR12 by Treatment Regimen and Liver Disease179/17932/33178/17833/33181/18231/32179/17936/3612-Week Treatment24-Week TreatmentNote: subgroup results do not include patients who withdrew consent or were lost to follow-upSource: Afdhal N, et al. N Engl J Med. 2014;370:
24 INVESTIGATIONAL3D (ABT-450/r-Ombitasvir + Dasabuvir) + Ribavirin GT 1 and Compensated Cirrhosis: TURQUOISE-II StudyTURQUOISE II: SVR12Source: Poordad F, et al. N Engl J Med. 2014;370:
25 HCV Treatment: Key Concepts Very high SVR rates with new therapiesExcellent SVR rates regardless of cirrhosis, raceExcellent SVR rates in treatment experiencedGenotype 3 is most difficult to treatAll oral therapies wave of futureCost of new therapies is huge barrier
26 University of Washington: Hepatitis C Online Hepatitis C Online:
29 HIV TestingWhich one of the following best describes the initial recommended HIV screening test in the 2014 CDC recommendations?A. 4th generation p24 antigen-antibody assay B. Western blot C. HIV RNA
30 Traditional Approach to HIV Diagnostic Testing InitialSupplementalEIAWestern blot or IFAOptimized for SensitivityOptimized for SpecificityDrawbacks with Conventional HIV Diagnostic AlgorithmDoes not detect acute HIVDoes not differentiate HIV-1 and HIV-2Problems with indeterminate Western blot
31 Laboratory Diagnosis of Early HIV Infection HIV AntibodyHIV RNAHIV p24 antigenTiming of HIV RNA, HIV p24 antigen, and HIV Antibody
32 4th Generation HIV Ag/Ab Combination Assays HIV p24 AntigenHIV AntibodiesDetects HIV-1 p24 antigen and antibodies to HIV-1 and HIV-2
33 2014 CDC Recommendations Recommended Laboraatory HIV Testing Algorithm HIV-1/2 Antigen/Antibody Combination Immunoassay(+)(-)Negative for HIV-1 and HIV-2 antibodies and p24 AgHIV-1/HIV-2 Ab Differentiation ImmunoassayHIV-1 (+) HIV-2 (-)HIV-1 (-) HIV-2 (+)HIV-1 (+) HIV-2 (+)HIV-1 (-) or Indeterminate HIV-2 (-)HIV-1 antibodies detectedHIV-2 antibodies detectedHIV antibodies detectedHIV-1 NATHIV-1 NAT (+)HIV-1 NAT (-)Acute HIV-1 infectionNegative for HIV-1Source: Centers for Disease Control and Prevention
35 US Health and Human Services (HHS) May 1, 2014 Antiretroviral Therapy Guidelines Source: 2014 HHS Antiretroviral Therapy Guidelines. AIDS Info (www.aidsinfo.nih.gov)
36 HHS Antiretroviral Therapy Guidelines: 2013 Initiating Therapy in Treatment-Naïve Patients Antiretroviral therapy (ART) is recommended for all HIV-infected individuals to reduce the risk of disease progression.Recommend (BIII)500Strongly Recommend (AII)350Strongly Recommend (AI)Source: 2013 HHS Antiretroviral Therapy Guidelines. AIDS Info (www.aidsinfo.nih.gov)
37 HIV Prevention Trials Network (HPTN) Study 052 1,763 HIV Serodiscordant Couples (97% heterosexual)-++-n = 873n = 890Source: Cohen M, et al. N Engl J Med. 2011;36:
38 HIV Prevention Trials Network (HPTN) Study 052 ++550Early Therapy CD cells/mm3350250Deferred Therapy CD4 < 250 cells/mm3 or AIDS Related EventSource: Cohen M, et al. N Engl J Med. 2011;36:
39 HIV Prevention Trials Network (HPTN) Study 052 96% ReductionP < 0.001Source: Cohen M, et al. N Engl J Med. 2011;36:
40 HHS Antiretroviral Therapy Guidelines: May 1, Recommended Regimens Regardless of Baseline HIV RNA or CD4 CountClassTherapyPill BurdenNNRTI-BasedEfavirenz-Tenofovir-EmtricitabinePI-BasedAtazanavir + Ritonavir + Tenofovir-EmtricitabineDarunavir + Ritonavir + Tenofovir-EmtricitabineINSTI-BasedRaltegravir + Tenofovir-Emtricitabine^Elvitegravir-Cobicistat-Tenofovir-EmtricitabineDolutegravir + *Abacavir-LamivudineDolutegravir + Tenofovir-Emtricitabine^Elvitegravir-Cobicistat-Tenofovir-Emtricitabine: only for patients with pre-ART CrCl ≥ 70 ml/min *Abacavir recommended only if HLA-B5701 negativeSource: 2014 HHS Antiretroviral Therapy Guidelines. AIDS Info (www.aidsinfo.nih.gov)
41 Single Tablet Antiretroviral Regimens Efavirenz-Tenofovir-EmtricitabineAtriplaRilpivirine-Tenofovir-EmtricitabineCompleraElvitegravir-Cobicistat-Tenofovir-EmtricitabineStribild
42 Dolutegravir Phase 3 Studies in Treatment-Naïve Subjects StudyARV HistoryComparisonResults1 SPRING-2ARV-NaïveDolutegravir QD versus RaltegravirNon-inferior (88% versus 85%)2 SINGLEDolutegravir QD versus EfavirenzDolutegravir superior (88% versus 81%)3 FLAMINGODolutegravir QD versus Darunavir-RTVDolutegravir superior (90% versus 83%)1 Raffi F, et al. Lancet 2013;381: Walmsley S. N Engl J Med. 2013:369: Clotet B, et al. Lancet March 31 [Epub ahead of print].
43 Future Single Tablet Regimen Dolutegravir-Abacavir-Lamivudine“Tri Pill”
45 2013Source: Kuhar DT, et al. Infect Control Hosp Epidemiol ;34:
46 Case History HIV Exposure in a Health Care Worker A 41-year-old male nurse has a needlestick injury on his left thumb. The site bled for about 2 minutes after the injury. The source patient has documented HIV infection, has never taken antiretroviral medications, and most lab studies showed HIV RNA level of 2,350 copies/ml and CD4 count of 658 cells/mm3.Based on USPHS 2013 Guidelines, what is recommended? A. 2 drugs: Zidovudine-lamivudine B. 2 drugs: Tenofovir-emtricitabine C. 3 drugs: Tenofovir-emtricitabine + Raltegravir D. 3 drugs: Tenofovir-emtricitabine + Darunavir + ritonavir
47 2013 USPHS Occupational PEP Guidelines Number of Antiretroviral Medications to Use “…the PHS working group recommends prescribing 3 (or more) tolerable drugs as PEP for all occupational exposures to HIV.”Source: Kuhar DT, et al. Infect Control Hosp Epidemiol ;34:
48 Raltegravir (Isentress) 400 mg twice daily 2013 USPHS Occupational PEP Guidelines Recommendations for Antiretroviral RegimensRecommended Antiretroviral Regimens for Occupational PEP (28-Day Duration)Preferred RegimenINSTINNRTIPill BurdenRaltegravir (Isentress) 400 mg twice dailyTenofovir-Emtricitabine (Truvada) 1 pill dailySource: Kuhar DT, et al. Infect Control Hosp Epidemiol ;34:
49 Post-Exposure Prophylaxis Line (PEPline) 888-448-4911
51 HBV Treatment and Entecavir Resistancne What percentage of patients with chronic HBV and long term entecavir treatment will develop resistance?
52 Resistance with Entecavir 222 nucleoside-naïve patients treated for 3 years - Cumulative -resistance to entecavir of 1.3% at 3 years Yuen MF, et al. Am J Gastroenterol. 2011;106:474 nucleoside-naïve treated for 4 years - Cumulative resistance to entecavir of 0.4% Ono A, et al. J Hepatol. 2012;57:508.Overall Estimates of Resistance Rates - Treatment naïve: < 1% at 5 years - Prior lamivudine failure: approximately 50% at 5 years
53 Duration of HBV Therapy with Entecavir Can you stop entecavir after long-term treatment (> 2 years) for patients with HBeAg- chronic HBV and HBeAg- and sustained virologic suppression?
54 Duration of HBV Therapy with Entecavir Background patients with HBeAg- chronic HBV - On entecavir for ≥ 2 years - Undetectable HBV DNA on ≥3 occasions 6 months apartFollowing Entecavir Cessation - Virologic relapse at 24 weeks: 74% - Virologic relapse at 48 weeks: 91% “…therapy should be continued indefinitely until the recognised treatment endpoint of HBsAg seroclearance.”Source: Seto WK, et al. Gut. 2014; May 15 [E pub Ahead of Print]
Your consent to our cookies if you continue to use this website.