HCV genotype and HBV co-infection associate with HCV clearance in HIV-positive subjects

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


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

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s


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


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%)


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)


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


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


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


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


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.


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


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

HCV genotype and HBV co-infection associate with HCV clearance in HIV-positive subjects

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