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Hepatitis B and Hepatitis C Co-infections with HIV in Vietnam: Now – And Tomorrow’s Cures

This article explores the background, importance, burden, interventions, and current/pipeline treatments for hepatitis B and hepatitis C co-infections with HIV in Vietnam.

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Hepatitis B and Hepatitis C Co-infections with HIV in Vietnam: Now – And Tomorrow’s Cures

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  1. Hepatitis B and Hepatitis C Co-infections with HIV in Vietnam: Now – And Tomorrow’s Cures Siobhán O’Connor, MD, MPH Senior Medical Officer for Global Health Division of Viral Hepatitis U.S. Centers for Disease Control and Prevention

  2. Outline Background and importance, Vietnam context Burden, Vietnam context Interventions: Integrated HIV programs and treatment as prevention Current and pipeline treatments for hepatitis C virus and hepatitis B virus Conclusions

  3. Hepatitis B Virus Co-infection with HIV Factors and Effect 1Thio, AIDS 2012. 2Thio, Lancet2002. 3Konopnicki, AIDS 2005. 4Hoffmann, AIDS 2009. 5The Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Study Group, AIDS 2010. 6Dore, AIDS.2010. 7Chun, J Infect Dis, 2012. 8De Vries-Sluijs, Gastroenterology 2010. 9Mendes-Correa, BMC Infect Dis 2011. 10Martín-Carbonero, AIDS 2011. 11Avihingsanon, AIDS Res Ther 2012. 12Zoutendijk, J Infect Dis 2012. 13De Vries-Sluijs, Gastroenterology 2010. 14Tsuchiuya, Epidemiol Infect 2013. 15Stockdale, Clin Infect Dis 2015. 16Soriano, AIDS 2015.

  4. Hepatitis C Virus Co-infection with HIVFactors and Effect 1Sereno L, J Int Assoc Physicians AIDS Care 2012. 2Sulkowski M. Hepatology 2014.

  5. High Risk Groups Hepatitis B VirusPopulation Prevalence Influences Risk Vietnam Population ~10-12% HBV-infected + ~15-40% Susceptible to HBV S HIV+ ~48-75% immune to HBV I HIV– The 6th National Scientific Conference on HIV/AIDS

  6. High Risk Groups Hepatitis B VirusPopulation Prevalence Influences Risk Vietnam Population ~10-12% HBV-infected + ~15-40% Susceptible to HBV S HIV+ ~48-75% immune to HBV I + SS IIII HIV– The 6th National Scientific Conference on HIV/AIDS

  7. Hepatitis C VirusInfluences on Risk Group Prevalence Vietnam Population High Risk Groups X% Susceptible to HCV S ~1-4% HCV + HIV+ HIV– The 6th National Scientific Conference on HIV/AIDS

  8. Hepatitis C VirusInfluences on Risk Group Prevalence Vietnam Population High Risk Groups X% Susceptible to HCV S ~1-4% HCV + HIV+ + SSS HIV– The 6th National Scientific Conference on HIV/AIDS

  9. Hepatitis B Virus and Hepatitis C VirusTransmission in High Risk Groups • Vietnam: people who inject/injected drugs (PWID), men who have sex with men (MSM), female sex workers • HCV transmission – Internal >>> External • HBV transmission – External & Internal PWID MSM HBV HBV FSW HCV HCV The 6th National Scientific Conference on HIV/AIDS

  10. HIV, HBV and HCV Among Male IDU Vietnam, 2009-10 IBBS*1, 10 provinces *Integrated Behavioral and Biologic Survey, conducted by NIHE. 1Nadol PJ, PLoS ONE 2015.

  11. 2010 Integrated Behavioral and Biologic Survey: Men Who Have Sex with Men1,2 Unpublished – Under review 1Nadol P, et al. High Hepatitis C Virus (HCV) Prevalence among Men Who Have Sex with Men (MSM) in Vietnam and Associated Risk Factors: 2010 Vietnam Integrated Behavioral and Biologic Survey [Under review]. 2Conducted by NIHE. The 6th National Scientific Conference on HIV/AIDS

  12. HBV and HCV amongHigh Risk Groups and HIV-infected • 2010 Integrated Behavioral and Biologic Survey* • 53% hepatitis B virus (HBV) load >20,000 IU/ml1 Genotypes B and C • 71% hepatitis C virus (HCV) Ag/Ab+ were RNA+1 Genotypes 1 >>> 6 > 3 > 2(consistent with published convenience samples2,3) – Implications for treatment • Data in-progress HCV among HCMC sex workers (FHI, MoH) Tenofovir-based ART impact: HIV, HBV, HCV in HCMC (Provincial AIDS Committee, Tropical Disease Hospital) *Integrated Behavioral and Biologic Survey, conducted by NIHE. 1Nadol P, et al. High Hepatitis C Virus (HCV) Prevalence among Men Who Have Sex with Men (MSM) in Vietnam and Associated Risk Factors: 2010 Vietnam Integrated Behavioral and Biologic Survey [ Under review]. 2Dunford L, PLoS ONE 2012. 3Wasitthankasem R, PLoS ONE 2014. The 6th National Scientific Conference on HIV/AIDS

  13. Hepatitis B Virus and Hepatitis C Virus Surveillance: High Risk Groups • Vietnam 2012-13 Integrated Biological and Behavioral Survey (Round III)*# People who inject(ed) drugs (PWID), men who have sex with men (MSM), female sex workers (FSW) Hanoi, Hai Phong, Ho Chi Minh City Active and past hepatitis B virus infection (HBV) • Still susceptible to HBV (not immune) Active HCV infection and past HCV infection • Hepatitis C core antigen replaces HCV RNA (novel) *Implemented by NIHE, with CDC assistance; #Analysis in-progress The 6th National Scientific Conference on HIV/AIDS

  14. Hepatitis B Virus and Hepatitis C VirusTransmission Among High Risk Groups • People who inject/injected drugs (PWID), men who have sex with men (MSM), female sex workers • HCV transmission – Mostly Internal • HBV transmission – External & Internal PWID X MSM HBV HBV X X FSW HCV INTERVENTION HCV X The 6th National Scientific Conference on HIV/AIDS

  15. Interventions to Prevent HIV and HCV Among Persons Who Inject Drugs ++ sufficient data; + tentative data; +: Inconclusive; * : no data 1MacArthur GJ, Int J Drug Policy 2014. The 6th National Scientific Conference on HIV/AIDS

  16. Hepatitis C Virus (HCV) DAA*Treatment as Prevention (TasP)1 1Martin, Hepatology 2013.. Prevalence in many US cities falls close to 50%-65% Treating just 8% of active injectors per year would reduce prevalence by 50% to 90% in 15 years *Direct Acting Antivirals

  17. Value of Comprehensive Prevention:TasP*, Syringe Access and Opioid Substitution1 *TasP = treatment as prevention, OST = opioid substitution treatment, HCNSP = syringe access programs 1Martin, Clinical Infectious Diseases, 2013.

  18. HCV Direct-acting Antivirals (DAA)Approved and in Clinical Trials *May require pegylated-Interferon Black = Approved by U.S. Food and Drug Administration and the European Commission. Blue = European Commission approved. 1Asselah T, Hepatology 2015 (Suppl 2, EASL 2015). The 6th National Scientific Conference on HIV/AIDS

  19. Hepatitis C Virus: Direct-acting Antivirals (DAAs)Treat to “Cure” (SVR) • All oral (interferon-free), well-tolerated (ribavirin-free) • High sustained viral response rates (SVR) >> interferon • <12-week to 24 week courses • Some once daily – improves adherence • New pan-genotypic combinations achieve SVR >90% in all genotypes (e.g., 1, 6, 3, 2) No genotyping?1-5 • Costs decreasing: India licensed generic cost of 4 weeks [sofosbuvir + ribavirin] may be USD150 1Universty of Washington, http://www.hepatitisc.uw.edu/. 2AASLD, http://www.hcvguidelines.org/full-report/unique-patient-populations-patients-hivhcv-coinfection). 3NIH, AIDSinfo (https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv-guidelines/26/hiv-hcv). 4Nelson DR, Hepatology 2015. 5Asselah T, Hepatology 2015 (Suppl 2, Abstract P1332, EASL 2015). The 6th National Scientific Conference on HIV/AIDS

  20. Key Issues: Direct-acting Antiviral (DAA) HCV Treatment in Vietnam • HCV treatment IS EFFECTIVE with HIV co-infection1-3 Monitor ART* interactions: tenofovir toxicity (ledipasvir); other3 Review other ART interactions • >90% genotype 1 (GT1), GT6 and GT2 responses (major GT circulating in Vietnam) – GT3 was less responsive1-3 New pangenotypic regimens improve GT3 response: >90%1-5 • Cirrhotics need longer treatment, +/- ribavirin & treatment restrictions for HIV/HCV cirrhotics1-5 Early treatment is best!!!! *ART=HIV-suppressive antiretroviral therapy. ^SVR = sustained viral response. 1Universty of Washington, http://www.hepatitisc.uw.edu/. 2AASLD, http://www.hcvguidelines.org/full-report/unique-patient-populations-patients-hivhcv-coinfection). 3National Institutes of Health, AIDSinfo (https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv-guidelines/26/hiv-hcv ). 4Nelson DR, Hepatology 2015. 5Asselah T, Hepatology 2015 (Suppl 2, Abstract P1332, EASL 2015). The 6th National Scientific Conference on HIV/AIDS

  21. Care and Treatment CascadePrevents Morbidity and Transmission(Treatment as Prevention [TasP]) Hepatitis C Cascade Early entry into care Early DAA treatment Early diagnosis CURE Infection X Transmission Medicines Patent Pool (MPP, UNITAID) includes licensed generic HCV direct-acting antivirals (DAAs) HIV and HCV morbidity The 6th National Scientific Conference on HIV/AIDS

  22. Hepatitis B Treatment: SuppressionU.S. Food and Drug Administration Approved 1Adapted from Hepatitis B Foundation, Drug Watch, http://www.hepb.org/professionals/hbf_drug_watch.htm. The 6th National Scientific Conference on HIV/AIDS

  23. Hepatitis B Treatment: SuppressionIn Clinical Trials 1Adapted from Hepatitis B Foundation, Drug Watch, http://www.hepb.org/professionals/hbf_drug_watch.htm. The 6th National Scientific Conference on HIV/AIDS

  24. Hepatitis B Treatment PipelineProlonged Suppression, Eliminate Infection 1Adapted from Hepatitis B Foundation, Drug Watch, http://www.hepb.org/professionals/hbf_drug_watch.htm. The 6th National Scientific Conference on HIV/AIDS

  25. Hepatitis B Treatment PipelineImmune Enhancers to Eliminate 1Adapted from Hepatitis B Foundation, Drug Watch, http://www.hepb.org/professionals/hbf_drug_watch.htm. The 6th National Scientific Conference on HIV/AIDS

  26. Care and Treatment CascadePrevents Morbidity and Transmission(Treatment as Prevention [TasP]) Majority Suppress HIV and HBV morbidity Transmission Hepatitis B Cascade Early entry into care Early diagnosis Manage +/- Treat Infection CURE Pipeline X Transmission The 6th National Scientific Conference on HIV/AIDS

  27. ConclusionsHBV and HCV Mono-infections, Co-infections with HIV • Hepatitis C virus (HCV) / Hepatitis C Pangenotypic cure feasible now – costs declining • Hepatitis B virus (HBV) / Hepatitis B • First line tenofovir-based ART; care for HBV mono-infection • Similarities with HIV 90-90-90 EARLY test/diagnose – Early care/manage – Access treatment • Treatment as Prevention + prevention programs • Reduce HBV, HCV-associated HIV morbidity/mortality • Reduce HBV and HCV transmission The 6th National Scientific Conference on HIV/AIDS

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