Marion Peters August 2020 ARS Question 1 Which statement is true about HCVHIV Treatment of HIV HCV coinfection differs from HCV monoinfection HCV Ab protects against reinfection with HCV Spontaneous clearance is common after acute HCV infection in PLWH ID: 1038209
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1. Breakout sessionRyan WhiteMarion PetersAugust 2020
2. ARS Question 1:Which statement is true about HCV/HIVTreatment of HIV/ HCV coinfection differs from HCV monoinfectionHCV Ab protects against reinfection with HCVSpontaneous clearance is common after acute HCV infection in PLWHHCC occurs after cure of HCV
3. Case 163 AA male with HTN, hyperlipidemia and HIV referred for abnormal LFTsExam and key labs:AST 63 ALT 52 Cr 0.8 PLT 78 ALB 3.4 INR 1.1 Tbili 0.9 Meds:omeprazole 20 mg QD, HCTZ, rosuvastatin 5mgDolutegravir, TAF and 3TC
4. Evaluation of Abnormal LFTs in PLWHLiver Tests: -Function: Albumin, bilirubin, INR -Inflammation: AST, ALT -Cholestasis: Alk Phos, bilirubin -portal HTN: platelets, WBCCommon liver diseases:HBV: HBsAg, anti-HBs, anti-HBc -alcoholHCV: HCV Ab, HCV RNA -drug toxicityNAFLD: Fasting glucose, TG, cholesterol, Hgb A1cLess commonMetabolic: Iron, Tsat, ferritin (hemochromatosis), Ceruloplasmin (Wilson Disease)Autoimmune diseases: AMA, IgM (for PBC), ASMA, ANA, IgG (for AIH)A1AT phenotypeHepatotoxicityVaccination status for HAV (IgG) and HBVLiver imaging and fibrosis assessmentFibrosis: APRI: AST/Platelet ratio;FIB-4 (AST, ALT, plt, age);Fibroscan, ARFI (ultrasound)Liver biopsyImaging –only if PHTN
5. Fibrosis AssessmentAPRI: AST/Platelet ratio; 2.02= cirrhosisFIB-4 (AST, ALT, plt, age); 7.06 = cirrhosisFibroscan, ARFI (ultrasound)Liver biopsy not neededImaging –only useful to diagnose fibrosis severity if PHTNUltrasound: nodular liver with splenomegalyHCV RNA 5 million
6. Case 163 AA male HTN, hyperlipidemia HIV and HCV GT1aCirrhosis based on FIB-4 and nodular liver on imaging with splenomegalyHCV RNA 5 millionExam and key labs:Abd: No ascites. No asterixisPLT 78 ALB 3.4 INR 1.1 Tbili 0.9 AST 63 ALT 52 Cr 0.8 (CTP A6)Meds:omeprazole 20 mg QD, HCTZ, rosuvastatin 5mgDolutegravir, TAF and 3TC
7. Treatment-Naive Genotype 1a with HIV and Compensated CirrhosisRecommended regimens listed by evidence level and alphabeticallyDaily fixed-dose combination of elbasvir (50 mg)/grazoprevir (100 mg) for patients without baseline NS5A RASsb for elbasvir12 weeksI, ADaily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg)12 weeksI, ADaily fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg)12 weeksI, ADaily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg)c8 (12) weeks (HIV)I, Bb Includes genotype 1a RASs at amino acid position 28, 30, 31, or 93 known to confer antiviral resistance. If 1 or more RASs are present, another recommended regimen should be used.c Dosing is 3 coformulated tablets (glecaprevir [100 mg]/pibrentasvir [40 mg]) taken once daily.
8. Recommended treatment HCV simplified without cirrhosis- not for HIV HCV coinfected Genotype 1-6:Glecaprevir (300 mg) / pibrentasvir (120 mg) to be taken with food for a duration of 8 weeks Genotype 1, 2, 4, 5, or 6Sofosbuvir (400 mg) / velpatasvir (100 mg) for a duration of 12 weeksNOTE: Patients with genotype 3 require baseline NS5A resistance-associated substitution (RAS) testing. Those without Y93H can be treated with 12 weeks of sofosbuvir/velpatasvir. If Y93H is present, see HCV guidance for treatment recommendations.
9. Drug drug interactionsOmeprazole with SOF/LED (take together on empty stomach)Omeprazole with SOF/VEL (take DAA with food then PPI 4 hours later)Rosuvastatin- do not use with SOF/LED or SOF/VEL/VOXYou don’t need to remember, you only need to CHECKHCVguidelines.orgUniversity of Liverpool: https://www.hep-druginteractions.org/checker
10. How to follow upNo liver follow upFollow up for concommitant diseaseFollow up for cirrhosis
11. Case 1 HCV Cured but still a liver problemCirrhotic so needs q6 monthly AFP and imagingFibroscan 29kPA and CAP 380So cirrhotic with portal HTN and steatosisObesity, HTN, HLD, steatosisHgb A1c 6.5% fasting glucose 125- borderline diabetesControl weight (diet and exercise), diabetes, cholesterolHealthy life style, limit alcohol, THC not daily
12. ARS Question 2:Which statement is true in NAFLD and PLWHFatty liver disease is uncommon in PLWHLiver Fibrosis is uncommon in PLWH with NAFLDFibroscan can measure fat and fibrosis ART does not lead to weight gain
13. Transient Elastography
14. Elastography: Fibroscan2.5 kPaAffected by weight, access of probe (2 cm), steatosis
15. TimeMotionAmplitudeVCTE: Probe Selection Guidance31 mmSkin To Capsule DistanceXL XLProbe Selection Tool
16. Problems with VCTE (Fibroscan)False positiveAcute inflammation (ALT>100)RejectionCholestasisHepatic congestionNon fasting stateAlcoholHard to estimateToo fatToo thinVessels False negativeHCV after cureVuppalanchi, Hepatology, 2017Requires adequate experience to produce reliable resultsAt least 50 scans reviewed by expert
17. What Does CAP Measure?Controlled attenuation parameterUltrasound Attenuation Rate(signal reduction rate)Unit: dB/M(decibels per meter)
18. ARS Question 3Which statement is true IN PLWH/HBVHBeAg positivity is lower in PLWHAfter acute HBV, loss of HBsAg is more common in PLWH than HIV negCurrent HBV therapies usually lead to loss of HBsAg ART initiation leads to loss of HBsAg in PLWH
19. Case 224 yo MSM HIV diagnosed 1990HBsAg positive 1997 (HBV DNA 9.62 log c/mL)ART with LAM became anti-HBc positive alone2004 diffuse large B cell lymphoma treated with steroids and CHOPIssues to considerJournal of Clinical Virology 39 (2007) 48–50
20. HAART: lamivudine, efavirenz, lopinavir/ritonavirJournal of Clinical Virology 39 (2007) 48–50SteroidCHOPHBcAb+++++HBsAg--+++HBeAg--+++HBsAb-----HBeAb-----HIV load (log10 copies/mL)<1.69<1.69<1.69CD4+ (/mm3)307270390SadefovirNHL DgHBV DNANHL recurrenceLODALT
21. Lymphoma in HIV HBV patient24 yo MSM HIV diagnosed 1990HBsAg positive 1997 (HBV DNA 9.62 log c/mL)ART with LAM became anti-HBc positive alone2004 diffuse large B cell lymphoma treated with steroids and CHOP6 weeks later he reverse seroconverted to HBsAg positiveDelay in chemotherapyAdefovir added with dramatic decline in HBV DNA load and a normalisation of hepatic enzyme levels.Journal of Clinical Virology 39 (2007) 48–50
22. Reactivation of HBV in HIVHigh rate of reactivation in immunosuppressed patients ChemotherapyHIV after immune reconstitutionPost organ transplant Biologic response modifiers: rituximab (anti-CD20), TNF- inhibitorsLymphoma increased in HIV patientsEven in those who have lost HBsAg and are positive for anti-HBc +/- anti-HBs
23. ERBuddingPlus strandsynthesisMinus strandsynthesisRNApackaging(encapsidation)TranslationTranscriptionRepair RecyclingEntrycccDNANucleusHost RNA polReverse transcriptase P proteinpre-genomic RNAS, C, P,e synthesisHBsAg posViral Life Cycle
24. ERcccDNANucleusHBsAg negAnti-HBsAnti-HBcImmune system considers this “recovered” BUT cccDNA is template for viral replicationViral Life Cycle- “latent or recovered” HBV
25. Strategies to Eradicate HBVVirologic approachesEntry inhibitorsBlock cccDNATranscription inhibitorsRNA interferenceHBV capsid inhibitorPolymerase inhibitorsSecretion inhibitorsHost immune approachesInterferonsRIG-I agonists- d/c hepatotoxicityTLR 7/8PD-1/ PDL-1IL-7Therapeutic vaccinesImmune complex vaccinesNasal HBV (NASVAC) vaccinesDNA vaccinesT cell vaccinesAdenovirus based vaccines (TG1050)Yeast based vaccines
26. Peters and Locarnini Gastro and Hep 2017MYRPreclinsiRNAs Ph1-2CpCAMNAPNAP