HBV/ HCV COI NFECTI ONS I N PATI ENTS WI TH HI V Dr Reena Harania - - PowerPoint PPT Presentation

HBV/ HCV COI NFECTI ONS I N PATI ENTS WI TH HI V

Dr Reena Harania MBBS, MRCP, MSc Infectious Disease

Adults and children estimated to be living with HI V as of end 2005

Total: 40.3 million 25.8 million in Sub-Saharan Africa Kenya Prevalence 6.7%

Western & Central Europe

720 000

[570 000 – 890 000]

North Africa & Middle East

510 000

[230 000 – 1.4 million]

Sub-Saharan Africa

25.8 million

[23.8 – 28.9 million]

Eastern Europe & Central Asia

1.6 million

[990 000 – 2.3 million]

South & South-East Asia

7.4 million

[4.5 – 11.0 million]

Oceania

74 000

[45 000 – 120 000]

North America

1.2 million

[650 000 – 1.8 million]

Caribbean

300 000

[200 000 – 510 000]

Latin America

1.8 million

[1.4 – 2.4 million]

East Asia

870 000

[440 000 – 1.4 million]

HBsAg Prevalence

≥8% - High 2-7% - Intermediate <2% - Low

Geographic Distribution of Chronic HBV Infection

CDC

United States 3-4 M Americas 12-15 M Africa 30-40 M Southeast Asia 30-35 M Australia 0.2 M

World Health Organization. Weekly epidemiological record. 1999;74:421-428.

Western Europe 5 M

170-200 Million (M) Carriers Worldwide

Hepatitis C: A Global Health Problem

Eastern Europe 10 M Far East Asia 60 M

HI V/ HBV/ HCV TRANSMI SSI ON

Virus Means of transmission

HIV Sexual, Vertical, Blood transfusion, IDU, traditional procedures Hepatitis B Sexual, mother-to-child, blood exposure (transfusion, IDU, tattoo) Hepatitis C Blood exposure (transfusion, IDU, tattoo); sexual, mother-to-child less common

Karuru, Lule et al

SUB GROUP HCV HI V HI V-HCV co- infection

Blood donors

0.79% 1.07% 0.02%

Clinical Hosp Staff

5.2%

• Non-clinical Hosp

Staff

2.5%

• HI V/ AI DS patients

3.7% 3.7%

HI V-ve patients

4.4%

• VCT clients

0% 9.3% 0%

HCV

 Lule et al in 1995 found the prevalence rate

• f HCV to be 2.8% among patients with

chronic liver disease in Kenyatta National Hospital.

 Mwangi (1998), found a prevalence rate of

1.8% in blood donors.

Pregnant women in Kenya HBV

 2241 pregnant women enrolled  9.3%

HepBsAg + ve (205)

 8.8%

HepBeAg + ve

 Okoth FA, Mbuthia J et al EAMJ, 2006

HBV

 Ogotu et al, in 1990, found that 12.2% of 40

consecutive patients with AIDS were HBsAg positive, 24.4% were HBsAb positive and 75.6% were HBcAb positive

 This is in comparison with 6-10% HBsAg

positivity in the general population.

A OTEDO

 Screened patients with jaundice-519  Excluded 185

• ther causes

 Recruited 334

47% HBV + ve HIV-ve



53% HBV + ve HIV+ ve

 HBV infection is much more common than

HCV in Kenya and globally

OBJECTI VES

• To determine the prevalence of HCV and HBV

infection among HIV/AIDS patients presenting to AKUH, Nairobi

• To identify possible risk factors
• To assess response of Co-infections to

HAART

WHY?

 Share transmission routes  Interactions of viruses  Treatment decisions  Drug interactions

Hepatitis C

HI V/ HCV CV CO COI NFECT CTI ON

 10% -30% w HIV also have HCV (Western

data)

 Rate of HCV depends on risk factor

– Hemophiliacs – > 90% – IDUs – 70% -90% – MSM – 5% -10%

HCV/ HI V Coinfection

 HIV accelerates Hep C liver disease (may

cut time to cirrhosis in half!)

 Hep C may impair immune reconstitution

after HAART

 HCC may occur at an earlier age with

coinfection

Hepatitis C

HI V/ HCV CV CO COI NFECT CTI ON

 HCV liver disease is more severe in HIV+  HCV liver disease is now more important

– HIV deaths are decreasing – Deaths related to liver disease are increasing

 Effect of HCV infection on HIV/AIDS

progression is not known

Drug interactions in Co- infection

 ddI and d4T plus interferon/ribavirin

appear to cause mitochondrial toxicity

 result: lactic acidosis, peripheral

neuropathy

 Avoid starting these drugs if plan to treat

HCV later

Acute Hepatitis C Chronic Hepatitis 75%-85 % Cirrhosis 20 %

10-20 years

Hoofnagle JH Hepatology. 1997;26 (suppl 1): 15S-20S Di Bisceglie, Hepatology, 2000

Natural History of Hepatitis C

Most patients with chronic HCV infection are asymptomatic

Hepatitis B

 Acute and chronic forms

– 2-10% develop chronic disease over 5 years of age

 Asymptomatic or symptomatic

– Clinical illness < 5 yrs of age: < 10% (jaundice) > 5 yrs of age: 30% -50%

 Incubation: 45 – 180 days

– Average 60-90 days

 Most common cause of cirrhosis and

hepatocellular carcinoma worldwide

CDC

Risk of Chronic Disease if Untreated/Unvaccinated

 Neonates

90-100% HBsAg +

 Children

20- 40% HBsAg +

 Adults

< 5% HBsAg +

 Nearly 40% of children with chronic

hepatitis B will develop end-stage liver disease in 20-30 years

 Peters M 9th CROI Seattle, 2002

Hepatitis B Serologies

 HBsAg

– acute disease or – chronic carrier

 HBsAb:

– past infection or – vaccinated

 Hbcore Ab (HBcAb) IgM: acute infection  HBcore Ab total: past infection

– Combined IgM & IgG serology

Hepatitis B(e) Serologies

 HBe Ag: more infectious  HBe Ab: less infectious

– Marker of treatment response – Determines treatment duration

Symptoms HBeAg HBe Ab

Core Total Ab Core IgM HBs Ab HBs Ag

Weeks after Exposure Titer

4 8 12 16 20 24 28 32 36 52 100

Acute Hepatitis B Virus Infection: RECOVERY

CDC

Weeks after Exposure Titer

IgM anti-HBc Core Total Ab HBsAg Acute (6 months) HBeAg Chronic (Years) anti-HBe 4 8 12 16 20 24 28 32 36 52 Years

Chronic Hepatitis B Virus Infection

CDC

HIV Co-infection Increases the Risk

• f ESLD due to HBV

 MACS, 4,967 men

– HIV, 47% – HBV, 6% (n= 326) – HIV/HBV, 4.3% (n= 213)

 HIV/HBV: 17-fold higher

risk of liver death compared to HBV alone

– Alcohol – Low CD4 – Increased risk after 1996

Liver Mortaility by HIV and HBV Status

0.8 1.7 14.1 5 10 15 No HIV

• r HBV

HBV

• nly

HIV

• nly

HIV and HBV Thio C et al. Lancet 2002;360:9349.

Hepatitis B and HIV Co-infection

 Higher HBV DNA viral loads than with HBV

alone

 Higher mortality with HIV co-infection  Hepatic damage with uncontrolled HIV  Immune reconstitution increases hepatic

injury due to inflammatory response

– Peters M 9th CROI Seattle, 2002

Chronic Hepatitis B Treatment: FDA-approved

 Alfa interferon; pegylated interferon  Lamivudine (Epivir HB)

– HBV rebound possible if lamivudine stopped

 Adefovir (Hepsera) - active against lamivudine-

resistant HBV; pilot study

– N = 35; 5.15 log10 decrease in viral load – Mean CD4+ 423 cells/cmm – Benhamou Lancet 2001:358

 Entecavir (Baraclude)

– Active against lamivudine-resistant HBV

Dual Hepatitis B/HIV Co-infection Therapies

 Lamivudine (Epivir)  Off-label uses

– Emtricitabine (Emtriva) – Tenofovir DF (Viread) – active against lamivudine-resistant HBV – Truvada (emtricitabine/tenofovir)

METHODOLOGY

 HIV POSITIVE CONSECUTIVE PATIENTS  CONSENT OBTAINED  QUESTIONNAIRE FILLED RE-RISKS  BLOOD OBTAINED FOR FBC LFTs CD4 VL

HepBsAG HCVab

METHODOLOGY 2

HepBsAg + ve : HBV VL, HepBeAg HCV – Viral load Started on ARVs if required

TOTAL RECRUI TED – 378

 HIV ONLY

351 93%

 HIV/HBV

23

6%

 HIV/HCV

4

1%

Demographics: ALL PATI ENTS

Patients with HI V/ HBV Co infection

HI V/ HBV

 males being co-infected is 3 times that of

females, which is statistically significant 95% range of the odds ratio ranges from 1.1 to 8.3.

HI V/ HCV

ETHNI C GROUPS

HBV/ HI V CO I NFECTI ON BY ETHNI CI TY

Distribution of the HCV patients by ethnic group.

Kikuyu Luo Kamba Ugandan

Sum m ar ary HI V posit ive an and co-infect ion ( H ( HI V and HBsAg posit ive)

HIV+ve, HBsAg-ve HIV+ve, HBsAg+ve Total P-value

• No. of patients

351 23 374 <.0001 Age (yrs) Mean (±SD) 39.2(±8.15) 42.7(±9.13) 39.5(±8.30) 0.05

HI V/ HBV BY GENDER

20 40 60 80 100 120 140 160 180 200 MALE FEMALE HIV ONLY HIV/HBV P=0.024

HI V ONLY VERSUS HI V/ HBV

 NO DIFFERENCE IN THE 2 GROUPS IN

TERMS OF

 VIRAL LOAD

P= 0.25

 CD4 COUNTS

P= 0.405

 LFTS

P= 212

HI V ONLY VERSUS HI V/ HVC

 ONLY 4 PTS HAD HIV/HCV COINFECTION  M:F

1:3

 Deranged LFTs

3

 Patients with HIV/HCV infections were

fewer, more females (75% ), were more likely to have abnormal LFTs although none

• f these were statistically significant.

 Only 1 patient admitted – homosexual  No intravenous drug users



• nly HIV

HBV co-infection HCV co-infection P-value

• No. of patients

351 (93%) 23 (6%) 4 (1%) <.0001 Age (yrs) Mean (±SD) 39.2(±8.15) 42.7(±9.13) 42.5(±14.01) 0.128

Logarithm of HI V Viral Load

9.3(±3.47) 9.6(±2.71) 11.0(±2.03) 0.591

CD4

230.1(±237) 180.6(±174.9) 292.0(±125) 0.529 Gender Female 161 ( 45.87%) 5 ( 21.74%) 3( 75.00%) 0.037 Male 190 ( 54.13%) 18 ( 78.26%) 1( 25.00%) Liver Function Normal 137 ( 39.03%) 12 ( 52.17%) 1( 25.00%) 0.383 Abnormal 214 ( 60.97%) 11 ( 47.83%) 3( 75.00%)

CD4 counts by HBV- versus HBV+ status

HIV Viral Load by HIV only and HIV/HBV infections

• nly HIV

HBV co-infection P-value Circumcision No 215( 61.43%) 13( 56.52%) 0.640 yes 135( 38.57%) 10( 43.48%) Education primary 31( 9.54%) 0( 0.00%) 0.343 secondary 105( 32.31%) 6( 31.58%) tertiary 189( 58.15%) 13( 68.42%) HepB_vaccination no 286( 81.71%) 23(100.00%) 0.024 yes 64( 18.29%) 0( 0.00%) Transfusion No 293( 83.95%) 20( 86.96%) 0.703 Yes 56( 16.05%) 3( 13.04%)

Comparing only HIV infection and HBV co-infection by the risk factors

Comparing only HIV infection and HCV co-infection by the risk factors

• nly HIV

HCV co-infection P-value Circumcision No 215 ( 61.43%) 3( 75.00%) 0.579 yes 135 ( 38.57%) 1( 25.00%) Education primary 31 ( 9.54%) 0( 0.00%) 0.189 secondary 105 ( 32.31%) 3( 75.00%) tertiary 189 ( 58.15%) 1( 25.00%) HepB_vaccination no 286 ( 81.71%) 4(100.00%) 0.345 yes 64 ( 18.29%) 0( 0.00%) Transfusion No 293 ( 83.95%) 2( 50.00%) 0.068 Yes 56 ( 16.05%) 2( 50.00%)

HEPBsAG+ ve 23

 HEPBeAG+ ve

17% (4)

 HEPBeAG-ve

83% (19) (p = 0.0018).

 70 % of HEPBsAG (HBV+ ) patients used

ARVs: 16

ARVs USED BY PATI ENTS HI V/ HBV CO I NFECTI ON

4% 40% 26% 30% CBV/NVP CBV/STO TRU/STO Other

HBV viral load before and after treatment p = 0.0031

Before After Frequency <60 60-10,000 >10,000 Total <60 1 1 60-10,000 2 6 8 >10,000 3 1 4 Total 5 7 1 13

Before After Frequency <60 60-10,000 >10,000 Total <60 1 1 60-10,000 1 1 >10,000 3 1 4 Total 3 2 1 6

TRU/STO had marked improvement in HBV viral load (p = 0.0828).

Use of TRU/ STO combination against any

• ther treatment for the HBV co-infected

(p= 0.0218)

DI SCUSSI ON

 HIV/HBV COMMON 6%  HIV/HBV MORE COMMON IN MALES AND

GREATER THAN 35 YEARS

 (MAYBE MISSED PTS WITH HEP B CORE

IGM + VE)

 HIV/HBV RESPONSE TO TREATMENT  HIV/HCV LESS COMMON 1%

Week 1 Week 2 Week 3 Week 4 Week 8 Week 12 Week 16 Week 20 Week 24 Lam for 24 wks then ADD TDF TDF 245 mgOD Lam and TDF 245 mgOD P=0.045 Error bars are 95% CI of the slope Using DAVG analysis

Change in log10 HBVDNA from baseline

• 1
• 2
• 3
• 4
• 5
• 6
• 7

TDF/3TC more effective than 3TC alone in drug-naïve HIV/HBV co-infected

Nelson M, et al. 13th CROI, Denver, CO, February 5-8, 2006. Abst. 831

Similar Anti-HBV Activity of Tenofovir and Adefovir in Coinfected Patients



Interim data from ACTG A5127: HBV/HIV-1 coinfected pts

– HBV DNA ≥ 100,000 – Stable antiretroviral therapy; HIV-1 RNA ≤ 10,000



Reduction in HBV DNA with tenofovir noninferior to adefovir

Peters M, et al. Abstract 124.

HBV DNA (log10)

2 4 6 8 10 20 40 60 80 90 Weeks 48 Adefovir Tenofovir DF

Recommendations

 TEST ALL HIV PAITENTS FOR HBV Co-

infection

 VACCINATE  ?HCV TESTING IN OUR SET UP (COST)  ?TREAT WITH TNF/FTC RATHER THAN

LAMIVUDINE ALONE.

THANK YOU

Only Hbcore Ab Positive (Total IgG + IgM)

 HBs antigen and HBs antibody negative  Common with HIV co-infection  IgM component negative with chronic

disease

 May be carrier (chronically infected),

despite negative HBsAg

– Can distinguish by hepatitis B DNA PCR

Where are we now in Hepatitis B

 No requirement for HAART-Pegylated Interferon 

• Adefovir



• Entecavir

 Requirement for HAART

Where are we now in Hepatitis B

 No requirement for HAART-Pegylated Interferon 

• Adefovir



• Entecavir

 Requirement for HAART  Lamivudine Failures

Current HBV status of HIV/HBV coinfected patients

1/11 6/19 12/21 18/21 4/28 12/38 24/41 33/42

20 40 60 80 100

HBV-DNA<1000 copies/mL ALT<45 U/L loss Hbe-antigen loss HBs-antigen

proportion of patients (%) TDF+3TC TDF

Criteria for Treatment

 American Association for the Study of Liver

Diseases

 AST/ALT > 2 times ULN  HBV DNA PCR > 100,000 c/ml  Liver histology showing moderate or

severe hepatitis

Lok A et al. Hepatology 2004;39,(3).

Rebound Hepatitis

 Associated with removal of hepatitis B

therapy

 Could occur inadvertently with change

in HIV therapy for virologic failure

– Consider maintaining HIV therapy with activity against HBV when changing ART

Incidence of LAM Resistance in HBV and HBV/HIV Patients

20% 49% 47% 67% 38% 90% 0% 20% 40% 60% 80% 100% 1 2 3 4 HIV negative HIV positive

Benhamou et al., Hepatology, 1999)

Hepatitis C

HI V/ HCV CV CO COI NFECT CTI ON

 HIV treatments can cause liver

problems/liver enzyme elevations

– In some studies these liver problems are increased in those w/HCV

 Some report worsening of HCV liver disease

after HIV treatment is started

Chronic Hepatitis B

 10-20% will develop cirrhosis  25% of these will develop decompensated liver

disease

 6-15% of those with chronic disease will

develop hepatocellular carcinoma

 HBV not directly cytopathic to hepatocytes  The host immune response causes much of the

damage

– Peters M 9th CROI Seattle, 2002

Risk factors for Hepatitis C infection

20% 10% 5% 55% 10% IVDU Cocaine Exposure to infected sex partner or multiple partners Occupational, hemodialysis, household, perinatal No recognized source

http://www.cdc.gov/ncidod/diseases/hepatitis/c_training/edu/transmission modes; 2000