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 Eastern Europe Western & Central & Central Asia Europe 1.6 million North America 720 000 East Asia 1.2 million [990 000 – 2.3 million] [570 000 – 890 000] 870 000 [650 000 – 1.8 million] North Africa & Middle East Caribbean [440 000 – 1.4 million] 510 000 300 000 South & South-East Asia [230 000 – 1.4 million] [200 000 – 510 000] 7.4 million Sub-Saharan Africa [4.5 – 11.0 million] Latin America 25.8 million Oceania 1.8 million [23.8 – 28.9 million] 74 000 [1.4 – 2.4 million] [45 000 – 120 000] Total: 40.3 million 25.8 million in Sub-Saharan Africa Kenya Prevalence 6.7%
Geographic Distribution of Chronic HBV Infection HBsAg Prevalence ≥ 8% - High 2-7% - Intermediate <2% - Low CDC
Hepatitis C: A Global Health Problem 170-200 Million (M) Carriers Worldwide Far East Asia 60 M Eastern Western Europe Europe 10 M United States 5 M 3-4 M Southeast Asia 30-35 M Africa Americas 30-40 M 12-15 M Australia 0.2 M World Health Organization. Weekly epidemiological record. 1999;74:421-428.
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 2.5% - - Staff 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 of 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 other 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
Natural History of Hepatitis C Most patients with chronic HCV infection are asymptomatic Acute Hepatitis C 10-20 years Chronic Hepatitis 75%-85 % Cirrhosis 20 % Hoofnagle JH Hepatology. 1997;26 (suppl 1): 15S-20S Di Bisceglie, Hepatology, 2000
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 9 th 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
Acute Hepatitis B Virus Infection: RECOVERY Symptoms HBe Ab HBeAg Core Total Ab Titer HBs Ab Core IgM HBs Ag 0 4 8 12 16 24 28 32 52 100 20 36 Weeks after Exposure CDC
Chronic Hepatitis B Virus Infection Acute Chronic (6 months) (Years) HBeAg anti-HBe HBsAg Core Total Ab Titer IgM anti-HBc Years 0 4 8 12 16 20 24 28 32 36 52 CDC Weeks after Exposure
HIV Co-infection Increases the Risk of ESLD due to HBV MACS, 4,967 men Liver Mortaility by HIV – HIV, 47% and HBV Status – HBV, 6% (n= 326) 14.1 – HIV/HBV, 4.3% (n= 213) 15 10 HIV/HBV: 17-fold higher risk of liver death 5 1.7 compared to HBV alone 0.8 0 0 – Alcohol No HIV HBV HIV HIV – Low CD4 or HBV only only and – Increased risk after 1996 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 9 th 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 log 10 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% 6% HIV/HBV 23 1% HIV/HCV 4
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, HIV+ve, Total P-value HBsAg-ve HBsAg+ve No. of patients 351 23 374 <.0001 39.2( ± 8.15) 42.7( ± 9.13) 39.5( ± 8.30) Age (yrs) Mean 0.05 ( ± SD)
HI V/ HBV BY GENDER 200 180 160 140 120 HIV ONLY 100 HIV/HBV 80 P=0.024 60 40 20 0 MALE FEMALE
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 of these were statistically significant.
Only 1 patient admitted – homosexual No intravenous drug users
only HIV HBV HCV P-value co-infection co-infection <.0001 No. of patients 351 (93%) 23 (6%) 4 (1%) Age (yrs) Mean ( ± SD) 39.2( ± 8.15) 42.7( ± 9.13) 42.5( ± 14.01) 0.128 9.3( ± 3.47) 9.6( ± 2.71) 11.0( ± 2.03) Logarithm of HI V 0.591 Viral Load 230.1( ± 237) 180.6( ± 174.9) 292.0( ± 125) CD4 0.529 Gender 161 ( 45.87%) 5 ( 21.74%) 3( 75.00%) 0.037 Female 190 ( 54.13%) 18 ( 78.26%) 1( 25.00%) Male Liver Function 137 ( 39.03%) 12 ( 52.17%) 1( 25.00%) 0.383 Normal 214 ( 60.97%) 11 ( 47.83%) 3( 75.00%) Abnormal
CD4 counts by HBV- versus HBV+ status
HIV Viral Load by HIV only and HIV/HBV infections
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