Washington D.C., USA, 22-27 July 2012www.aids2012.org HCV genotype and HBV co-infection associate with HCV clearance in HIV- positive subjects Yuan Dong,

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Washington D.C., USA, July 2012www.aids2012.org HCV genotype and HBV co-infection associate with HCV clearance in HIV- positive subjects Yuan Dong, Chao Qiu, Xueshan Xia, Jing Wang, Haiyan Zhang, Yongheng Wang, Xiaoyan Zhang, Jianqing Xu Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Fudan University, Shanghai, China

Washington D.C., USA, July 2012www.aids2012.org Chronic liver disease is increasingly contributing to morbidity and mortality among people with HIV, particularly HCV- related liver disease Dominique Salmon-Ceron,et al. Journal of Hepatology, 2009, 50: E. Rosenthal, et al. Journal of Viral Hepatitis, 2007, 14:

Washington D.C., USA, July 2012www.aids2012.org Jialun Zhou, et al, Journal of Gastroenterology and Hepatology, 2007, 22: Greub G, et al. Lancet Nov 25;356(9244): HCV prevalence in people with HIV (TAHOD, TREAT Asia HIV Observational Database; &The Swiss HIV Cohort study)

Washington D.C., USA, July 2012www.aids2012.org Background It remains unknown the associations of HCV clearance in HIV-positive Chinese IDUs. Less is known about whether and how HCV genotypes affect its clearance.

HIV-HCV co-infection prevalence among IDUs in China 0 Yunnan (46.3%) Myanmar Thailand Laos Vietnam Xinjiang (36.2%)

Washington D.C., USA, July 2012www.aids2012.org Study Objectives To determine the prevalence of HCV infection, spontaneous clearance and genotype distribution among HIV-positive IDUs from Yunnan, a region with the highest HIV-HCV co-infection prevalence in China. To search for factors that may affect the clearance of HCV and whether HCV genotypes could exert different influences on those factors.

HIV-positive IDUs were recruited in Yunnan Province ( Dali CDC, Compulsory detoxification, Labor camp ) Interview Sociodemographic information, high-risk behaviors and history of HIV-infection and medication Blood collection CD4 T cell count (FACSAria flow cytometry; BD Bioscience), ALT,TB Anti-HCV Ab (ELISA; Kehua Company) HBsAb, HBsAg, HBeAg, HBeAb, HBcAb (ELISA; Wantai Company) HCV viral load (Realtime-PCR; PG Biotech Company) HCV genotyping (5’NCR/ NS5B/ E1–E2; ABI Prism 3100 genetic analyzer) Data analysis SPSS software (version 17.0)

Washington D.C., USA, July 2012www.aids2012.org Recruitment of HIV/HCV co-infected patients 529 HIV infected patients 47 HCV uninfected patients 24 newly infected HCV patients 1 had invalid data 457 HCV infected patients 98 HCV cleared patients359 HCV chronic infected patients 31 HBV uninfected 43 resolved HBV 24 chronic HBV 144 HBV uninfected 187 resolved HBV 28 chronic HBV

Washington D.C., USA, July 2012www.aids2012.org Demographic characteristics Serum HCV RNA CharacteristicTotalNegativePositive Number of cases457 (100)98(21.4)359 (78.6) Age, median (range)33.00 (18-47)34.00 (15-52) Sex Male, n (%)405 (88.6)86 (87.7)319 (88.8) Female, n (%)52 (11.4)12 (12.3)40 (11.2) Management Dali CDC, n (%)103 (22.5)20 (20.4)83 (23.1) Compulsory detoxification, n (%)259 (56.7)58 (59.2)201 (56.0) Labor camp, n (%)95 (20.8)20 (20.4)75 (20.9) Risk group Intravenous injection, n (%)452 (98.9)97 (98.9)355 (98.9) Sex, n (%)5 (1.1)1 (1.1)4 (1.1)

98/457(21.4) anti-HCV+ HIV+ subjects were HCV RNA- HCV prevalence, spontaneous clearance and genotype distribution 481/528 (91.1%) HCV infected among HIV+ 457/528 (86.6) anti-HCV+ among HIV +

VariableCleared HCV (%)Chronic HCV (%)OR (95%CI)P sex Male 86 (21.2)319 (78.8) Female 12 (23.1)40 (76.9) ( ) Age groups (y) <=3032 (26.2)90 (73.8) (21.1)210 (78.9)0.750 ( ) >=4010 (15.2)56 (84.8)0.502 ( ) HAART No 92 (21.0)346 (79.0) Yes 6 (33.3)12 (66.7) ( ) HBV coinfection uninfected31 (17.7)144 (82.3)1.00 Resolved43 (18.7)187 (81.3)1.068 ( ) Chronic HBV24 (46.2)28 (53.8)3.982 ( )< CD4 counts (cells/ul) <40039 (16.5)197 (83.5)1.00 >40053 (25.6)154 (74.4)1.738 ( ) ALT(u/ml) <=4059 (28.2)150 (71.8) (13.7)151 (86.3)0.404 ( ) >=8015 (20.5)58 (79.5)0.658 ( ) TB coinfection Uninfected, n(%)92 (21.3)340 (78.7) 1.00 Infected, n(%)6 (24.0)19 (76.0) ( ) Univariate analysis of correlates of HCV clearance

Washington D.C., USA, July 2012www.aids2012.org Multivariate logistic regression model for HCV clearance VariableOR (95% CI)P CD4 counts (cells/ul) < > ( ) HAART No1.00 yes2.865 ( ) HBV coinfection uninfected1.00 Resolved HBV0.977 ( ) Chronic HBV4.965 ( )< ALT(u/ml) <= ( ) >= ( ) The model was adjusted for age and gender

Washington D.C., USA, July 2012www.aids2012.org Clinical features of 231 HIV-infected patients with detectable HCV genotypes HCV genotype VariablesTotal136P CD4 counts (cells/μl) < (24.4)76(58.0)23(17.6) > (12.9)63(67.7)18(19.4) HBV coinfection Uninfected9922(22.2)65(65.7)12(12.1) Resolved HBV10615(14.2)70(66.0)21(19.8) Chronic HBV268(30.8) 10(38.5) ALT (u/ml) <=408116(19.8)48(59.3)17(21.0) (18.7)69(64.5)18(16.8) >=80439(20.9)26(60.5)8(18.6) HCV viral load < (19.5)104(65.4)24(15.1) > (19.4)39(54.2)19(26.4)0.1103

HCV genotype VariablesTotal3Non-3P HBV coinfection Uninfected9965(65.7)34(34.3) Chronic HBV268(30.8)18(69.2) Total13P HBV coinfection Uninfected8722(25.3)65(74.7) Chronic HBV168(50.0) Total6Non-6P HBV coinfection Uninfected9912(12.1)87(87.9) Chronic HBV2610(38.5)16(61.5) Total6Non-6P HCV viral load < (15.1)135(84.9) > (26.4)53(73.6) The appearance rate of different HCV genotype among HBV uninfected / chronic infected subjects

Washington D.C., USA, July 2012www.aids2012.org Conclusions The prevalence of HCV was 91.1% among HIV-infected IDUs, the spontaneous clearance rate was 21.4%. Our results suggested that the reserved host immune function (high CD4+T counts) and HBV co-infection (chronic HBV) could improve HCV clearance in HIV-infected IDUs whereas the damage in liver (high level of ALT) was associated with the non-clearance of HCV. We demonstrated that the clearance of different HCV genotypes might be facilitated by different factors. HBV chronic infection seemed to facilitate HCV genotype 3 clearance but not genotype 1 and 6. Further cohort studies are needed to determine the influences of HCV genotypes and HBV co-infection on the HCV spontaneous clearance.

Washington D.C., USA, July 2012www.aids2012.org We thank all the patients and investigators! Chao Qiu, Fudan University Xueshan Xia, Kunming University of Science and Technology Jing Wang, Fudan University Haiyan Zhang, Dali CDC Yongheng Wang, Dali CDC Guomei Sun, Fudan University Xiaoyan Zhang, Fudan University Jianqing Xu, Fudan University This work was supported by 973 program (2012CB519005) and National Grand Program on Key Infectious Disease Control (2012ZX ). Acknowledgements

Washington D.C., USA, July 2012www.aids2012.org

Washington D.C., USA, July 2012www.aids2012.org HCV genotype 1 infection stratified by CD4 counts HCV genotype VariablesTotal1Non-1P CD4 counts (cells/μl) < (24.4)99(75.6) > (12.9)81(87.1)0.0324