HIV and Hepatitis Co-infection. Martin Fisher Brighton and Sussex University Hospitals, UK

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1 HIV and Hepatitis Co-infection Martin Fisher Brighton and Sussex University Hospitals, UK

2 Useful References British HIV Association hiv_781.pdf European AIDS Clinical Society 2009

3 Overview Scope of the problem Epidemiology of co-infection HIV/HBV co-infection Impact on natural history Management of HBV in co-infected HIV/HCV co-infection Impact on natural history Management of HCV in co-infected Management of HIV in co-infected Other patient management issues

4 HIV/HBV/HCV Epidemiology Common routes of transmission Infected blood products Sharing needles Sexual contact High rates of co-infection 6-10% of European HIV patients HBV sag positive 10-50% of European HIV patients HCV infected

5 Natural History Of HBV Infection Exposure (Acute phase) 10% * HIV and Alcohol Resolved 90% * Stable Chronic 80% Slowly Progressive 75% 5-20% Cirrhosis 25% HCC Transplant Death (1-5%) * Very age dependent: 90% become chronic if infected vertically; 30% if <5yrs

6 Impact of HIV on HBV Impaired vaccine response Less spontaneous clearance Faster and more frequent progression to: Cirrhosis End-stage liver disease Hepatocellular carcinoma Death Increased development of resistance to HBV therapy

7 Natural History Of HCV Infection Exposure (Acute phase) 55-85% HIV and Alcohol Resolved 15% Stable Chronic 80% Slowly Progressive 75% 5-20% Cirrhosis 25% HCC Transplant Death (1-5%)

8 Impact of HIV on HCV? Increased susceptibility to infection Less spontaneous clearance Faster and more frequent progression to: Cirrhosis End-stage liver disease Hepatocellular carcinoma Death Impaired response to HCV treatment

9 Screening for HCV All HIV positive patients should be screened for HCV at diagnosis HCV antibody If HCV antibody positive: HCV RNA HCV genotype Also, if unexplained abnormal LFTs and risk of HCV (IVDU, MSM) and negative HCV antibody HCV RNA

10 Screening for HAV and HBV All HIV positive patients should be screened for HAV and HBV HAV IgG HBV sag and cab eag and HBV DNA if sag positive HBV DNA if abnormal LFTs and sag negative Delta antibody if sag positive

11 Vaccination All HIV positive patients should be considered for vaccination against HAV and HBV HAV if HAV IgG negative HBV if HBV cab negative, or if Cab positive and sabs < 10 Vaccination may be deferred until after initiation of HAART if CD4 < 200 If insufficient sab response (<10), consider Re-vaccination (and repeat when higher CD4 count) Double-strength vaccine Monitor sabs annually and re-vaccinate if <10 If failure to respond, check sag annually

12 Aims of treatment HIV: Long-term viral suppression Prevention of opportunistic complications HBV: (clearance) Long-term viral suppression Prevention of long-term consequences of liver damage HCV: Clearance Prevention of long-term consequences of liver damage

13 Management of HBV Immunomodulatory therapy: Interferon alpha Antiviral therapy: Lamivudine* Adefovir Entecavir * Tenofovir * (emtricitabine * ) (telbivudine?* ), (clevudine) Single or dual therapy? Hepatologists undecided. * Active against HIV at HBV dose

14 Management of the HBV/HIV coinfected patient Interferon therapy: Less effective +++ Ineffective at lower CD4 counts Little data in era of HAART Suppressive therapy:?use agents against HIV or not If yes, need to ensure full HIV suppression dual therapy against HBV recommended

15

16 Aim for undetectable HBV DNA by months Monitor HBV annually

17 Assessment of the HCV Coinfected patient Hepatitis C: HCV RNA and genotype? Assessment of liver damage Liver biopsy (or fibroscan) HIV: CD4 count HAART regimen (if on HAART) Patient readiness for treatment Mental health and psychosocial issues Ongoing drug use / risk behaviour

18 Patterns of Viral Response to IFN and Ribavirin Baseline Treatment Follow-up Nonresponder HCV RNA Partial Nonresponder Relapse Relapse HCV RNA Undetectable 12 weeks Time Sustained Responder

19 When to start HCV Treatment Ensure CD4 count > 350 If on HAART, ensure appropriate ART Modify if potential drug interactions If genotype 2/3 (i.e. favourable response: 45-75%) Offer treatment to all Biopsy not usually performed If genotype 1/4 (i.e. poorer response: 15-45%) Consider treatment in all May chose to defer treatment if minimal fibrosis (F0/1) If treatment deferred, monitor fibrosis every 3 years

20 Duration of HCV Therapy

21 Management of the HCV/HIV coinfected patient Avoid drug-drug interactions ddi toxicity (absolute contraindication) d4t - toxicity AZT toxicity abacavir reduced ribavirin levels Pegylated interferon and weight-based ribavirin Laboratory monitoring FBC every 4 weeks CD4 every 12 weeks Anticipate significant reduction (though % stable) LFTs at baseline and every 12 weeks Monitor and support mental health

22 Management of HCV nonresponders Suboptimal initial treatment: Inadequate regimen: Standard interferon Short duration Lower dose of ribavirin Toxicity or adherence Optimal initial treatment: Relapse RNA ve at end of Rx Non-response No negative RNA Re-treat with: -optimal dosing -Treatment support Consider re-treatment;?72 weeks Wait for newer anti-hcv agents Optimise HIV management

23 Management of End Stage Liver Disease All patients with cirrhosis should have 6 monthly assessment to exclude HCC: Ultrasound scan Alpha fetoprotein All patients with cirrhosis should have endoscopic evaluation for oesophageal varices at baseline and every 1-2 years All patients with ESLD should be assessed by an experienced hepatologist Transplantation may be considered if HIV well-controlled

24 Acute HCV Ongoing transmissions in IDU where needle exchange not available Recent outbreaks of sexual transmission amongst men who have sex with men Almost all HIV infected Diagnosis: usually by investigation of routine abnormal LFTs as part of HIV monitoring Spontaneous clearance rate around 15% Management: Monitor HCV RNA monthly for 3-6 months If no suggestion of clearance offer early treatment (within 6 month of infection) weeks of pegylated interferon and ribavirin Clearance rates of 70-90% reported

25 Impact of HBV and HCV on HIV HBV: No effect on HIV progression No effect on response to HAART HCV: No effect on HIV progression No effect on virological response to HAART? Impaired CD4 response to HAART HBV and HCV: Increased hepatotoxicity to HAART

26 Treating HIV in the co-infected patient When to start HIV Treatment? Treat earlier may slow progression of HBV and HCV May improve response to treatment of HBV and HCV? Treat later reduces risk of hepatotoxicity reduces risk of drug-drug interactions (if treating HCV) Risk of immune reconstitution disease

27 Treating HIV in the co-infected What to start with patient avoid ARV drugs with highest rates of hepatotoxicity (HBV and HCV) avoid ARV drugs with drug-drug interactions (if treating HCV) Use ARV drugs with dual activity (if treating HBV) What to switch to As above, plus Continue HBV active drugs even if HIV resistance

28 Summary High rates of co-infection Hepatitis progression increased by HIV Treatment is complex Ideally shared expertise with HIV and hepatology specialists Prevention, vaccination, alcohol

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