THE 6 TH NATIONAL SCIENTIFIC CONFERENCE ON HIV/AIDS 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
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THE 6 TH NATIONAL SCIENTIFIC CONFERENCE ON HIV/AIDS Hepatitis B and Hepatitis C Co-infections with HIV in Vietnam: Now – And Tomorrow’s Cures Siobhán O’Connor,
The 6 th National Scientific Conference on HIV/AIDS FactorEffect HBV endemic country ▬ Early infection, before HIV HIV/HBV co-infection rates ≥ population rates HIV risk behaviors Risk for new HBV infection the 20-40% of adults still susceptible to HBV HIV infection Hepatitis B disease progression, with HBV replication /2 as likely to clear new, acute HBV infection 3 Tenofovir/lamivudine ART HBV load, ± fibrosis – NOT cured Hepatitis B Virus Co-infection with HIV Factors and Effect 1 Thio, AIDS Thio, Lancet Konopnicki, AIDS Hoffmann, AIDS The Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Study Group, AIDS Dore, AIDS Chun, J Infect Dis, De Vries-Sluijs, Gastroenterology Mendes- Correa, BMC Infect Dis Martín-Carbonero, AIDS Avihingsanon, AIDS Res Ther Zoutendijk, J Infect Dis De Vries-Sluijs, Gastroenterology Tsuchiuya, Epidemiol Infect Stockdale, Clin Infect Dis Soriano, AIDS 2015.
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THE 6TH NATIONAL SCIENTIFIC CONFERENCE ON HIV/AIDS
Hepatitis B and Hepatitis C Co-infections with HIV in Vietnam:
Now – And Tomorrow’s Cures
Siobhán O’Connor, MD, MPHSenior Medical Officer for Global Health
Division of Viral Hepatitis U.S. Centers for Disease Control and Prevention
The 6th National Scientific Conference on HIV/AIDS
Outline
1. Background and importance, Vietnam context
2. Burden, Vietnam context
3. Interventions: Integrated HIV programs and treatment as prevention
4. Current and pipeline treatments for hepatitis C virus and hepatitis B virus
5. Conclusions
The 6th National Scientific Conference on HIV/AIDS
Factor EffectHBV endemic country▬Early infection, before HIV
HIV/HBV co-infection rates ≥ population rates
HIV risk behaviors Risk for new HBV infection the20-40% of adults still susceptible to HBV
HIV infection Hepatitis B disease progression, with HBV replication1-14
1/2 as likely to clear new, acute HBV infection3
Tenofovir/lamivudine ART HBV load, ± fibrosis15-16 – NOT cured
Hepatitis B Virus Co-infection with HIV Factors and Effect
1Thio, AIDS 2012. 2Thio, Lancet 2002. 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.
The 6th National Scientific Conference on HIV/AIDS
Factor EffectHCV rates vary in general population1
The 6th National Scientific Conference on HIV/AIDS
The 6th National Scientific Conference on HIV/AIDS
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.
2010 Integrated Behavioral and Biologic Survey: Men Who Have Sex with Men1,2
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.
Hepatitis C virus (HCV) exposure (past or current infection) and active hepatitis B virus infection rates among men who have sex with men (MSM) in four provinces
HCV Ag/Ab = Either antigen or antibody to hepatitis C virus (past or current HCV infection, cannot distinguish) HBsAg = Hepatitis B surface antigen (current HBV infection) Pos = positive (infected); Neg = negative (not infected)
Unpublished – Under review
The 6th National Scientific Conference on HIV/AIDS
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
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
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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 Direct-acting Antivirals (DAA)Approved and in Clinical Trials
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
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
Lamivudine/3TC Epivir-HBV GlaxoSmithKlinePhiladelphia, PA
FDA approved, 1998
Telbivudine Tyzeka Novartis,Switzerland
FDA approved 2006
Tenofovir disoproxil fumarate
Viread Gilead SciencesFoster City, CA
FDA approved, 2008
The 6th National Scientific Conference on HIV/AIDS
Hepatitis B Treatment: SuppressionU.S. Food and Drug Administration Approved
Hepatitis B Treatment: SuppressionIn Clinical Trials
1Adapted from Hepatitis B Foundation, Drug Watch, http://www.hepb.org/professionals/hbf_drug_watch.htm.
Nucleos(t)ide analogs – DNA polymerase inhibitors1
AGX-1009(Tenofovir ODE)
Prodrug of tenofovir Agenix, Australia
Phase I in China
Clevudine Inhibits DNA polymerase
Bukwang, S. KoreaEisai, Japan
Approved, S. Korea
CMX157 Prodrug of tenofovir ContraVir Pharmaceuticals,Edison, NJ
Phase II
Tenofovir alafenamide (TAF)
Prodrug of tenofovir Gilead SciencesFoster City, CA
Phase III
The 6th National Scientific Conference on HIV/AIDS
1Adapted from Hepatitis B Foundation, Drug Watch, http://www.hepb.org/professionals/hbf_drug_watch.htm.
Non-nucleoside antivirals1
Myrcludex B Entry inhibitor Hepatera, Russia with Phase II, EuropeARC-520 RNAi gene silencer Arrowhead Research Corp Phase II/IIINVR-1221 Capsid inhibitor Novira Therapeutics Phase IIaSB 9200 Small molecule nucleic
TKM-HBV HBsAg inhibitor Tekmira, Canada Phase IAlinia (Nitazoxanide) Small molecule Romark Labs Preclinicaldd-RNAi compound Gene silencing Benitec, Australia and
Biomics, ChinaPreclinical
BSBI-25 cccDNA inhibitor Baruch S. Blumberg Inst. PreclinicalCpAMS HBV core protein Assembly Biosciences PreclinicalMore…………..
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Hepatitis B Treatment PipelineProlonged Suppression, Eliminate Infection
Hepatitis B Treatment PipelineImmune Enhancers to Eliminate
1Adapted from Hepatitis B Foundation, Drug Watch, http://www.hepb.org/professionals/hbf_drug_watch.htm.
Non-interferon immune enhancersABX 203 Therapeutic vaccine ABIVAX, France Phase IIb/III
GS-4774 Therapeutic vaccine Gilead Sciences with Globe Immune
Phase II
GS-9620 TLR7 agonist Gilead Sciences Phase II
CYT107 Immune modulator Cytheris, France Phase I/IIa
TG 1050 Immunotherapeutic Transgene, China Phase I
INO-1800 Therapeutic vaccine Inovio Phase I
The 6th National Scientific Conference on HIV/AIDS
Care and Treatment CascadePrevents Morbidity and Transmission
(Treatment as Prevention [TasP])
Pipeline
Hepatitis B Cascade
InfectionEarly
diagnosis
Earlyentry
into careManage+/- Treat
Majority Suppress HIV and HBV
morbidity
CURECURE
Transmission
X
Tran
smiss
ion
The 6th National Scientific Conference on HIV/AIDS
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