Upload
reegan
View
39
Download
0
Tags:
Embed Size (px)
DESCRIPTION
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 - PowerPoint PPT Presentation
Citation preview
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, 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, 22-27 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: 736-745E. Rosenthal, et al. Journal of Viral Hepatitis, 2007, 14: 184-188
0
20
40
60
80
100Liver related deathsAIDS related deathsother causes of death
Increased propotion of deaths due to liver disease
% o
f to
tal d
eath
s
0
20
40
60
80
100HCVHBV
Motality distribution by hepatitis status
% o
f liv
er-r
elat
ed d
eath
s
Washington D.C., USA, 22-27 July 2012www.aids2012.org
Jialun Zhou, et al, Journal of Gastroenterology and Hepatology, 2007, 22: 1510-1518
Greub G, et al. Lancet. 2000 Nov 25;356(9244):1800-5.
HCV prevalence in people with HIV (TAHOD, TREAT Asia HIV Observational Database; &The Swiss HIV Cohort study)
Total Heterosexual Homosexual IDU others0
20
40
60
80
100
No. (n=3111) (n=835) (n=1035) (n=1108) (n=133)
The Swiss HIV Corhot Study
% o
f HC
V p
reva
lenc
e in
AID
S pa
tien
ts
Total Heterosexual Homosexual IDU Blood others0
20
40
60
80
100
No. (n=1469) (n=818) (n=372) (n=71) (n=44) (n=164)
TAHOD
% o
f HC
V p
reva
len
ce in
AID
S p
atie
nts
Washington D.C., USA, 22-27 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
LaosVietnam
Xinjiang(36.2%)
Washington D.C., USA, 22-27 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 collectionCD4 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, 22-27 July 2012www.aids2012.org
Recruitment of HIV/HCV co-infected patients
529 HIV infected patients47 HCV uninfected patients
24 newly infected HCV patients1 had invalid data
457 HCV infected patients
98 HCV cleared patients 359 HCV chronic infected patients
31 HBV uninfected43 resolved HBV24 chronic HBV
144 HBV uninfected187 resolved HBV28 chronic HBV
Washington D.C., USA, 22-27 July 2012www.aids2012.org
Demographic characteristics
Serum HCV RNA
Characteristic Total Negative Positive
Number of cases 457 (100) 98(21.4) 359 (78.6) Age, median (range) 33.00 (18-47) 34.00 (15-52)SexMale, n (%) 405 (88.6) 86 (87.7) 319 (88.8)Female, n (%) 52 (11.4) 12 (12.3) 40 (11.2)ManagementDali 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 groupIntravenous injection, n (%) 452 (98.9) 97 (98.9) 355 (98.9)Sex, n (%) 5 (1.1) 1 (1.1) 4 (1.1)
0
20
40
60
80
100
genotype 1 genotype 3 genotype 6
6v
6u
6n
6a
3b
3a
1b
1a
Genotype 6 43(18.6%)
6a 1(0.4%)
6n 36(15.6%)
6u 3(1.3%)
6v 3(1.3%)
Genotype 6 43(18.6%)
6a 1(0.4%)
6n 36(15.6%)
6u 3(1.3%)
6v 3(1.3%)
Genotype 3 143(61.9%)
3a 44(19.0%)
3b 99(42.9%)
Genotype 3 143(61.9%)
3a 44(19.0%)
3b 99(42.9%)
Genotype 1 45 (19.5%)
1a 7 (3.0%)
1b 38(16.5%)
Genotype 1 45 (19.5%)
1a 7 (3.0%)
1b 38(16.5%)
21.4%
78.6%HCV RNA-HCV RNA+
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 +
4.5% 8.9%
86.6%
anti-HCV- HCV RNA+anti-HCV-anti-HCV+
Variable Cleared HCV (%) Chronic HCV (%) OR (95%CI) PsexMale 86 (21.2) 319 (78.8) 1.00
0.7607Female 12 (23.1) 40 (76.9) 1.113 (0.559-2.213)Age groups (y)<=30 32 (26.2) 90 (73.8) 1.00
0.25910.0853
31-39 56 (21.1) 210 (78.9) 0.750 (0.455-1.236)>=40 10 (15.2) 56 (84.8) 0.502 (0.229-1.101)HAARTNo 92 (21.0) 346 (79.0) 1.00 0.2188Yes 6 (33.3) 12 (66.7) 1.880 (0.687-5.145) HBV coinfectionuninfected 31 (17.7) 144 (82.3) 1.00Resolved 43 (18.7) 187 (81.3) 1.068 (0.641-1.779) 0.8001Chronic HBV 24 (46.2) 28 (53.8) 3.982 (2.039-7.775) <0.0001CD4 counts (cells/ul)
<400 39 (16.5) 197 (83.5) 1.00>400 53 (25.6) 154 (74.4) 1.738 (1.093-2.765) 0.0195
ALT(u/ml)<=40 59 (28.2) 150 (71.8) 1.0040-80 24 (13.7) 151 (86.3) 0.404 (0.239-0.683) 0.0007>=80 15 (20.5) 58 (79.5) 0.658 (0.346-1.250) 0.2010TB coinfectionUninfected, n(%) 92 (21.3) 340 (78.7) 1.00Infected, n(%) 6 (24.0) 19 (76.0) 1.167 (0.453-3.006) 0.7490
Univariate analysis of correlates of HCV clearance
Washington D.C., USA, 22-27 July 2012www.aids2012.org
Multivariate logistic regression model for HCV clearance
Variable OR (95% CI) P
CD4 counts (cells/ul)
<400 1.00
>400 1.881 (1.147-3.086) 0.0123
HAART
No 1.00
yes 2.865 (0.942-8.715) 0.0636
HBV coinfection
uninfected 1.00
Resolved HBV 0.977 (0.564-1.692) 0.9327
Chronic HBV 4.965 (2.419-10.192) <0.0001
ALT(u/ml)
<=40 1.00
40-80 0.370 (0.210-0.653) 0.0006
>=80 0.451 (0.218-0.935) 0.0321
The model was adjusted for age and gender
Washington D.C., USA, 22-27 July 2012www.aids2012.org
Clinical features of 231 HIV-infected patients with detectable
HCV genotypesHCV genotype
Variables Total 1 3 6 PCD4 counts (cells/μl)<400 131 32(24.4) 76(58.0) 23(17.6)>400 93 12(12.9) 63(67.7) 18(19.4) 0.1001HBV coinfectionUninfected 99 22(22.2) 65(65.7) 12(12.1)
Resolved HBV 106 15(14.2) 70(66.0) 21(19.8)
Chronic HBV 26 8(30.8) 8(30.8) 10(38.5) 0.0029ALT (u/ml)<=40 81 16(19.8) 48(59.3) 17(21.0)40-80 107 20(18.7) 69(64.5) 18(16.8)>=80 43 9(20.9) 26(60.5) 8(18.6) 0.9470HCV viral load<500000 159 31(19.5) 104(65.4) 24(15.1)>500000 72 14(19.4) 39(54.2) 19(26.4) 0.1103
HCV genotype
Variables Total 3 Non-3 PHBV coinfection Uninfected 99 65(65.7) 34(34.3)Chronic HBV 26 8(30.8) 18(69.2) 0.0013
Total 1 3 P
HBV coinfection
Uninfected 87 22(25.3) 65(74.7)Chronic HBV 16 8(50.0) 8(50.0) 0.0455
Total 6 Non-6 PHBV coinfection
Uninfected 99 12(12.1) 87(87.9)
Chronic HBV 26 10(38.5) 16(61.5) 0.0017
Total 6 Non-6 PHCV viral load
<500000 159 24(15.1) 135(84.9)
>500000 72 19(26.4) 53(73.6) 0.0411
The appearance rate of different HCV genotype among HBV uninfected / chronic infected subjects
Washington D.C., USA, 22-27 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, 22-27 July 2012www.aids2012.org
We thank all the patients and investigators!
Chao Qiu , Fudan UniversityXueshan Xia, Kunming University of Science and Technology Jing Wang, Fudan UniversityHaiyan Zhang, Dali CDCYongheng Wang, Dali CDCGuomei Sun, Fudan UniversityXiaoyan Zhang, Fudan UniversityJianqing Xu, Fudan University
This work was supported by 973 program (2012CB519005) and National Grand Program on Key Infectious Disease Control (2012ZX10001-006).
Acknowledgements
Washington D.C., USA, 22-27 July 2012www.aids2012.org
Washington D.C., USA, 22-27 July 2012www.aids2012.org
HCV genotype 1 infection stratified by CD4 counts
HCV genotype
Variables Total 1 Non-1 P
CD4 counts (cells/μl)
<400 131 32(24.4) 99(75.6)
>400 93 12(12.9) 81(87.1) 0.0324