HBV screening and management in HIV-infected children and adolescents

Transcription

1 HBV screening and management in HIV-infected children and adolescents Linda Aurpibul M.D. Research Institute for Health Sciences, Chiang Mai University

2 8% HIV and Hepatitis B Co-infection Among Perinatally HIV-infected Thai Adolescents 521 perinatally HIV-infected children and adolescents were screened Their mean current age was 14.8 years (SD 2.1) Hepatitis B serostatus Total Prevalence (95% CI) -Chronic Hepatitis B ( ) -Isolated core antibody ( ) -Resolved natural HBV infection ( ) -Having seroprotection from previous immunization ( )

3 Concern in HIV-infected adolescents with HBV co-infection Risk of transmission via sexual activity, IDU Risk of liver disease progression Long duration on ART It s time for transition to adult care sooner or later we need to let them go!

4 Case One HBs Ag positive in perinatally HIV-infected child on ART

5 History A 14.7 years old adolescent boy has been initiated on antiretroviral therapy (nevirapine-based regimen) since the year Date Wk Age (yr) Wt (kg) Ht (cm) CD4(%) VL (cp/ml) ART regimen 6 Aug (1) 167,605 GPO vir 20 Jan (6) < 50 (3TC+d4T+NVP) 25 Sep (25) < 50 GPO vir Z 15 Nov (20) <40 (3TC+ZDV+NVP)

6 History (cont ) On 15 Nov 2010 he participated in hepatitis B screening program. The following hepatitis B profile was obtained; HBs Ag positive Anti-HBs negative Anti-HBc positive

7 Q1: What is your advice for this boy? A. He has no immune against hepatitis B; hepatitis B vaccination is needed. B. He has to see hepatologist for further management C. Another blood draw to confirm HBsAg status is needed

8 Discussion Answer A is not appropriate as the boy might have chronic hepatitis B infection. Thus, he would not get any benefit from re-immunization. Answer B is not the good option, we might be able to do some more thing for him before making a consultation with other subspecialty Answer C is the best choice, he should be re-tested in order to determine hepatitis B serostatus (Chronic hepatitis B is defined as having HBs Ag positive for > 6 Mo)

9 Why mention HBV-HIV co-infection? In HIV-infected patients, HBV symptoms usually mild or asymptomatic. Rate of hepatitis B clearance is lower 20-40% of patients progress to chronic hepatitis B infection (HBs Ag positive for > 6 Mo) Could progress to liver cancer more rapidly than general population

10 Four phase of chronic hepatitis B (as described in HIV negative patients) HBeAg positive negative Liver inflammation determined by: -ALT level, -liver fibroscan, -liver biposy yes no Immune active Immune tolerant Chronic active Inactive carrier In HIV-positive patients, utility of this classification and frequency of each type are not yet known. British HIV Association guidelines for the management of co-infection with HIV-1 and hepatitis B or C virus HIV Med 2010;11:1-30

11 Immune tolerant phase is general seen in people infected in childhood

12 History (cont ) He was appointed to come to clinic on 7 Feb2011, but he did not appear due to his school activities. His uncle came to pick up ARV drugs for him and promised to bring him in for subsequent visit on 2 May May2011 HBs Ag positive Anti-HBe negative HBe Ag positive 2 May2011 AST 15 ALT 32 Note: Specimen left over was sent for HBeAg, anti Hbe, and liver transaminase

13 Q2: Will you modify ARV regimen for this boy? A No, there is no need as lamivudine is a potent anti-hbv agent, and he is currently HIV viral suppressed B Yes, his ARV regimen should compose of 2 drugs active against both HIV and HBV. C I am not sure what to do.

14 Discussion Answer A is not the best option according to the current knowledge. Answer B is the right answer If your answer is C.WAKE UP please! 3TC resistant HBV is observed in approximately 40% of patients after 2 years on 3TC and in 90% of patients after 4 years when it is used as the only active drug for HBV in coinfected patients. M204V develops at a rate of 25% per year (Benhamou, 1999)

15 Discussion What drug should be added? Drugs with anti-hbv and HIV activity Lamivudine Emtricitabine Tenofovir Entecavir (weak against HIV) Drugs with anti- HBV activity only Interferon Adefovir Telbivudine Tenofovir is effective at suppressing HBV DNA and may induced HBeAg seroconversion.

16 Q3: Any more test(s) to be performed at the time of treatment modification? A. yes, HBV DNA PCR ± HBV resistance testing B. yes, liver ultrasonography and/or fibroscan C. yes, anti-hav, anti-hcv, and delta virus D. no, none is necessary

17 Discussion HBV DNA measurement Arbitrary cut-off value 20,000 IU/mL (10 5 copies/ml) is associated with risk of progressive liver disease, and accepted threshold for treatment consideration is > 2,000 IU/mL Help in distinguish replicative from non-replicative chronic hepatitis B Essential in subsequent disease monitoring Liver fibrosis assessment (not recommended by gastroenterologist at our site) Could be done sometime later during follow-up period HBV resistance testing May be considered (if feasible) as a baseline evaluation for those previously exposed to anti-hbv drugs

18 Q4: How to determine efficacy of HBV treatment? A. Measure HBV DNA PCR level B. Look for HBe Ag seroconversion C. Follow ALT level D. Perform HBV resistant testing to see if there is a resistance mutation or not

19 Discussion Goal of treatment in HBV monotherapy: HBeAg seroconversion (from positive to negative, could be expected wk after HBV DNA become undetectable) Normalization of ALT Realistic goal in those with coinfection: To stop or delay progression of hepatic fibrosis by suppression of HBV replication to undetectable levels. HIV DNA testing is essential for monitoring of disease Response = undetectable HBV DNA within 48 weeks of treatment Primary nonresponse = having a < 1 log 10 IU/mL drop in HBV DNA level from baseline at 3 months on treatment ALT elevation is a less sensitive indicator of disease severity in patients with co-infection

20 Case Two All negative

21 History A 18.7 years old adolescent boy Perinatally HIV-infected, initiated on ART since 2002 Date Age (yr) Wt (kg) Ht (cm) CD4(%) VL (cp/ml) ART regimen 5 Nov (3) 516,619 GPO vir (3TC+d4T+NVP) 26 Apr Virologic failure 279(13) 9,905 IDV+LPV/r 4 Feb Simplify regimen 625(26) <50 Zilavir(3TC+ZDV) +LPV/r 11 Oct (24) <40

22 History (cont ) On 22 Nov 2010 he participated in hepatitis B screening program. He has a document of completed childhood vaccination including hepatitis B. 22 Nov 2010 HBs Ag negative Anti-HBs negative Anti-HBc negative

23 Q1: What is the most important message for this boy? A. Good news! He has no hepatitis B infection; there is nothing to be done now, but re-testing every years is advised once he becomes sexually active. B. He is at risk for hepatitis B infection as he has no immune against hepatitis B. HBV revaccination is recommended as his current CD4 is > 350 cells/ul C. He is considered as a HBV vaccine non responder, additional boosting would not be beneficial in this case. He should be counseled regarding the risk of HBV infection

24 Discussion Optimizing protection against hepatitis B is important in HIV-positive individual. Antibody responses to HBV vaccine are inferior and less likely to persist with time when compared to non-hiv population. Revaccination is recommended after being on ART and once the CD4 cell count is above 350 cells/ul

25 Q2: What is the HBV vaccine schedule will you advise for him? A. A single booster dose is sufficient B. 3 standard dose at 0, 2, 6 months, IM C. 3 standard dose at 0, 2, 6 months, ID D. 3 double doses at 0, 2, 6 months, IM

26 Discussion Additional HBV vaccine in HIV-infected adults with non-response to initial standard dose Study HBV vaccine Response rate Bloom 2009 C 1-3 standard dose, IM 29% Theodora 2008 D 3 double dose, IM 50.7% Cruciani 2009 E 1-2 double dose, IM 73% C JAIDS 2008;50: D JID2008;197: E Vaccine 2009;27:17-22.

27 Discussion HBV revaccination in HIV-infected children after immune recovery Study Age of participants HBV vaccine Response rate Lao-araya M 2007 A 10.1 ± 2.4 yrs 3 standard dose, IM 92.1% Bunupuradah T 2011 B 1-18 yrs 3 standard dose, ID 90.2% 3 standard dose, IM 92.3% Persistence of antibody was detected in approximately 70% of cases at 3 years after HBV re-vaccination. c Yearly anti-hbs level measurement and subsequent booster dose of HBV vaccine is advised if anti-hbv falls below 100 IU/L (BHIVA2010) A Vaccine 2007;25:5324-9, B Vaccine 2011; in press, c Vaccine 2011:29;

28 Case Three Antiretroviral naïve adolescent girl

29 History A 12 years old adolescent girl has just been diagnosed as HIV-positive after her presentation at a community hospital with severe pneumonia. She has a history of recurrent chronic otitis media since the age of 4. Failure to thrive (unexplained stunting) was documented. Her BW was 23.5 kg, Ht 131 cm, CD4 lymphocyte count 67 cells/mm 3 (2%), HIV RNA PCR 17,260 copies/ml She has been living with her aunt after her mother has passed away of unknown cause, her father had left for years without any contact.

30 Q1: Will you order hepatitis B profile for this case prior to ART initiation? A. no, it is not necessary at this moment B. yes, it will affect our decision on ARV regimen C. depends on her health care coverage

31 Discussion Rationale for HBV screening prior to ART initiation Uncertain history of hepatitis immunization Born to mother with hepatitis B carrier Older adolescents who might acquire both HIV and HBV via sexual transmission Population with high prevalence of hepatitis B infection

32 History (cont ) The following hepatitis B profile was obtained; 29 Nov2010 -HBs Ag positive Anti-HBs negative Anti-HBc positive

33 Q2: What should be the first line ARV regimen of choice for this girl? A. 3TC+d4T+NVP B. 3TC+TDF+EFV C. 3TC+TDF+LPV/r

34 Discussion A. nevirapine with potential hepatotoxicity could be used with caution! B two active drugs against both infection is advised C. PI-based regimen is not recommended to be used as a first regimen except for young children < 24 Mo who have been exposed to NNRTI (WHO2010)

35 Take home message Screen your new and old patients for Hepatitis B status For those with co-infection, provide 2 active agents against both infection to suppress both virus to undetectable levels, and reduce chance of developing viral resistance Follow those children for disease progression and liver outcome, AND don t forget to share with all of us whatever you learnt

36 Wat Chan,Chiang Mai, Thailand Thank you for your attention