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Challenges in HIV-HBV co-infection Dr Gail Matthews MBChB MRCP FRACP PhD Clinical Academic And Senior Lecturer, Kirby Institute, UNSW Australia & St Vincent’s.

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Presentation on theme: "Challenges in HIV-HBV co-infection Dr Gail Matthews MBChB MRCP FRACP PhD Clinical Academic And Senior Lecturer, Kirby Institute, UNSW Australia & St Vincent’s."— Presentation transcript:

1 Challenges in HIV-HBV co-infection Dr Gail Matthews MBChB MRCP FRACP PhD Clinical Academic And Senior Lecturer, Kirby Institute, UNSW Australia & St Vincent’s Hospital, Sydney Australia

2 Gilead: Advisory Board, Honoraria, Research Grants, Travel Sponsorship BMS: Speaker fee, Travel Sponsorship Abbvie: Advisory Board, Honoraia Merck: Speaker fee, Research Grants, Travel Sponsorship Roche: Travel Sponsorship, Speaker fee Disclosures

3 HIV-HBV: a huge global burden Kourtis AP et al. N Engl J Med 2012;366: HBV m HIV 35 m HIV-HBV ~2.6 million

4 13 years of tenofovir (TDF) Meta-analysis 23 studies 550 HIV-HBV patients on TDF Increasing suppression over follow-up in majority Little evidence of resistance Price et al, PLOs One 2013

5 All guidelines recommend TDF- containing ART as preferred regimen WHO ARV guidelines 2013

6 General agreement on when to start CD4< 500CD4 >500 DHSS (US) WHO Evidence of severe chronic liver disease EACS (Europe) If HBV DNA > 2000 IU/ml or ALT elevated BHIVA (UK) HBV DNA > 2000 IU/ml OR F=>2 by TE or biopsy

7 If the majority of HIV-HBV infected individuals can be treated with a highly potent drug with no resistance what are the challenges remaining?

8 Challenges remain …in resource limited settings …in resource rich settings

9 Challenges in resource limited settings Diagnosis and monitoring Access Mother-child transmission

10 Challenges in resource limited settings Diagnosis and monitoring Access Mother-child transmission

11 Lack of access to routine testing and monitoring >50% people live in countries with no free testing Only 4% low-income countries have ready access to testing Easterbrook et al Sem Liv Dis 2012 Testing accessible to >50% Testing anonymous Free to allFree to some Africa20%40%10%27% SE Asia29% 14% Europe86%55%27%55% World Hepatitis Alliance/WHO global survey 2009: Testing for HBV and/or HCV

12 Lack of access to routine testing and monitoring Limited access to HBsAg testing means many co-infected individuals not identified pre-ART Little understanding of natural history of co-infection in RLS Liver disease fibrosis assessment not readily available Widespread absence of virological monitoring by HBV DNA testing

13 Challenges in resource limited settings Diagnosis and monitoring Access Mother-child transmission

14 Access to TDF in LMIC is restricted First line ART in low and middle income countries 2008 Towards universal access. WHO progress report 2009

15 Although use is improving Trends in d4T, AZT and TDF use in first-line antiretroviral therapy regimens for adults in low- and middle-income countries, 2006–2011 Global update on HIV treatment WHO Tanzania: 3% HIV and 17% HIV/HBV on TDF regimen Hawkins IAC 2012

16 Challenges in resource limited settings Diagnosis and monitoring Access Mother-child transmission

17 Preventing mother-child transmission Screening of pregnant women for HBV is not routine in many countries Despite WHO Expanded Program of Immunisation universal infant vaccination is not ‘universal’ –56% in SE Asia –47% in India –57% Nigeria

18 Global and regional infant vaccination rates Thurz et al Nature Gastro 2012 ; 9; WHO/UNICEF estimates of third dose of HBV vaccine coverage

19 Preventing mother-child transmission Screening of pregnant women for HBV is not routine in many countries Universal infant vaccination is not ‘universal’ –56% in SE Asia –47% in India –57% Nigeria High HBV viral loads in HIV infected women increase the likelihood of perinatal transmission even in the setting of immunisation – TDF-containing ART should be prioritised

20 Challenges in resource rich settings Suboptimal efficacy Toxicity Eradication

21 Challenges in resource rich settings Suboptimal efficacy Toxicity Eradication

22 8-10% remain viraemic on tenofovir ? De Vries Slujis Gastroenterology 2010 Efficacy is never 100% 78% optimal suppression over 7 years Boyd et al Hepatology 2014

23 Persistent viraemia (n=25) Viral rebound (n=13) Blipper (n=24) Patterns of suboptimal response to TDF based therapy in HIV-HBV 165 HIV -HBV coinfected individuals followed for median of 4 years HBV DNA detectable in 20% study visits Matthews CID 2012

24 Factors associated with detectable HBV DNA On truvada based therapy at least 6 months Undetectable HIV RNA < 400 c/ml OR95% CIp-value Age (per 10 yrs) , HBeAg positive , 38.98< <95% adherent , HAART <2 yrs , CD4 < 200 cells/mm , Long term adherence is always a challenge Matthews CID 2012

25 Drivers of HBV viraemia on TDF? Neither genotypic or phenotypic resistance have been definitively described Replication or reservoir release? Virological (UDPS, SGA) and immunological studies may give insight

26 Challenges in resource rich settings Suboptimal efficacy Toxicity Eradication

27 TDF associated with bone and kidney toxicity Cooper R D et al. Clin Infect Dis. 2010;51: , Bedimo AIDS (7)

28 Strategies when TDF is contra-indicated? Reduce dose TDF Switch to entecavir (caution if LAM-R) Adefovir plus entecavir (?kidney disease) Peg-interferon (?advanced liver disease) ? Tenfovir Alafenamide (TAF)

29 Challenges in resource rich settings Suboptimal efficacy Toxicity Eradication

30 The final challenge Science 2014, 343,

31 Implications of persistent viraemia Management and incidence of flare Options for switch Cure strategies Virological Immunological New agents for cure Burden of disease Understanding natural history Role of GT Occult HBV HCC Access to drug National testing policies Universal and birth dose vaccination Challenges at many levels Epidemiology Clinical research Basic science Policy/ advocacy

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