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HIV/HBV coinfection in HIV-infected children

HIV/HBV coinfection in HIV-infected children. Pope Kosalaraksa, M.D. Department of Pediatrics Faculty of Medicine Khon Kaen University. Outline. Epidemiology – prevalence Coinfection and risk of transmission Natural history of HBV infection perinatally/adults HBV/HIV coinfection: clinical

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HIV/HBV coinfection in HIV-infected children

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  1. HIV/HBV coinfectionin HIV-infected children Pope Kosalaraksa, M.D. Department of Pediatrics Faculty of Medicine Khon Kaen University

  2. Outline • Epidemiology – prevalence • Coinfection and risk of transmission • Natural history of HBV infection perinatally/adults • HBV/HIV coinfection: clinical • HBV vaccine: seroprotection, booster • Treatment

  3. Hepatitis B infection • Asymptomatic >>> Symptomatic • Recover (immune) >> carrier >> >> cirrhosis >> cancer • HIV-infected children more rapid/severe than adult/non HIV children?

  4. HBV/HIV co-infection In adults: • higher level of HBV viremia • increase hepatotoxicity • increase liver-related morbidity and mortality In children: • little information • unique population (immune tolerant) • liver-related morbidity, mortality

  5. Epidemiology • 350 million: chronic HBV infection • 0.5–1.2 millions: die each year • Pregnant women (Africa) - prevalence : HBV monoinfection 4.0 - 17.1% : HBV/HIV coinfection 0.4 - 7.1%

  6. HIV/HBV co-infection in children Healy SA, et al. Expert Rev Anti Infect Ther 2013;11:251-63.

  7. HBV and HIV • Common transmission routes : perinatal : horizontal : parenteral : sexual • Higher prevalence of HBV infection in HIV than non-HIV population

  8. Risk of developing chronic HBV • Age at time of infection : Neonate (mother HBeAg+) up to 90% : After neonate – 5 years 20-30% : Immunocompetent adults < 5-10% • Maternal HBeAg/anti-HBe status : < 10% - HBeAg -ve/anti-HBe +ve

  9. HBV vaccine in HIV children • may have less protection : less robust initial immune response : waning of anti-HBs • After cART : poor restore anti-HBs : 1-40% had protective Ab >10 IU/ml

  10. Immune response to HBV vaccine in HIV children • International Maternal Pediatric Adolescent AIDS Clinical Trial group : 204 HIV children with cART : mean age - 9 years : history of 3 doses of a primary HBV vaccination : 24% had protective anti-HBs antibody : 45%- seropositive at 8 weeks after a booster Abzug MJ, et al. J Infect Dis 2009:200:935-46.

  11. Booster response in HIV children • 64 HIV-infected children : median age - 10 years : median cART - 31 months : complete HBV vaccination : no seroprotective Ab – 87% • Seroprotective Ab after booster : 17.0% after 1st dose : 82.5% after 2nd dose : 92.0% after 3rd dose Lao-Araya M, et al. Vaccine 2011;29:3977-81.

  12. Extrapolating from adults’ studies • HBV/HIV co-infected children : more active liver disease : more rapid progression to hepatic fibrosis and cirrhosis

  13. HBV infection perinatally

  14. Phases of chronic HBV infection

  15. Treatment of HBV in children • Not cytopathic • Immune response: hepatic damage • Immune tolerant phase - not recommended : high HBV DNA, normal ALT • Immune active phase - recommended : elevated ALT, mod-sever liver inflam. : non-invasive measures – transient elastography

  16. Treatment of HBV in HIV children • Concern: high risk progression to hepatic fibrosis • Hepatic foundation expert: treat all regardless phase of infection • Other group: same as non HIV children • No published guideline: indication for Rx. • Antiviral drugs (HBV) : IFN-α, nucleos(t)ide anlogue

  17. Antiviral drugs • IFN-α – preferred treatment, 26% efficacy - poor tolerant: flu-like symptom • Lamivudine (3TC), FTC - good safety profile - risk of resistance (monotherapy) • Adefovir - increase in serum creatinine • Entecavir, Tenofovir - high genetic barrier - high efficacy(78-86%)

  18. HBV monotherapy in HIV • Lamivudine (3TC) resistance1 : 50% within 2 years : >90% at 4 years • In children2 : 69% HBV DNA > 105copies/ml : rtM204V/I mutation – 75% 1. Healy SA, et al. Expert Rev Anti Infect Ther 2013;11:251-63. 2. Aurpibul L, et al. Pediatr Infect Dis J 2012;31:943-7.

  19. Antiviral agents for HBV

  20. Treatment strategy: HIV/HBV • Not require HBV treatment : use lamivudine sparing ART • Require HBV treatment : use tenofovir/lamivudine • Hepatic flare after starting ART : 25% in adults : in children – immunetolerant (unknown)

  21. HIV/HBV: summary • Similar transmission route, drugs • Effect of HBV disease progression • HBV vaccine response rate : low, need reimmunization • Choice of ARV – depend on HBV status • Long survival in HIV children : long-term effect of HBV?? • Screening and Prevention****

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