Occult hepatitis B virus (HBV) and hepatitis C virus (HCV)

viremia in women with and at-risk for HIV/AIDS

Taylor L, Gholam P, Delong A, Rompalo A, Klein R, Schuman P, Gardner L, Carpenter C

for the HIV Epidemiology Research (HER) Study Group

Background• Sensitive nucleic acid detection methods

reveal low levels HBV DNA in serum in absence HBsAg– Occult HBV viremia (OHBV) =

‘hidden’ HBV viral replication – HBcAb typically only detectable serological

marker of prior exposure though serologically negative cases reported

• Occult HCV viremia (OHCV) = HCV viremia in absence HCV Ab+

Limits of Knowledge To Date• Single time point analyses

– May misclassify acute infection with viremia prior to development HBsAg or HCV Ab, as occult infection

– May misclassify HBV during viral clearance with HBsAg loss, near clearance of HBV DNA, as OHBV

• Different assays, varied sensitivities – Reported OHBV 0 - 89%, OHCV 0 -13%

• HIV+ women understudied

Objectives

1. Assess prevalence OHBV and OHCV in women with and at-risk for HIV/AIDS

– To confirm true occult infections with persistent viremia, no serologic markers, repeat nucleic acid and serologic testing 2 distant time points

2. Examine demographic, behavioral, serological characteristics associated with OHBV and OHCV

Methods• HIV Epidemiology Research (HER) Study

• Multi-center, prospective, longitudinal study natural history HIV in women

• 1993 - 2000

• Enrolled 871 HIV+, 439 demographically matched HIV(-) at-risk women

• Ages 16 – 55

• Interviews conducted, plasma obtained semiannually

MethodsStudy population: subset with stored plasma• 845 (65%), 549 HIV+, 296 HIV(-) • Representative of entire cohort at baseline

– HIV+ (65% vs. 67%)– HCV Ab+ (54% vs. 57%)– HBcAb+ (52% vs. 54%)– HBsAg+ (2.6% vs. 2.5%)– All other demographic, biochemical,

serological characteristics comparable• 60% Black, 15% Latina, 1% Other, 22% White

Analyzed Data from 3 Timepoints 1st: Baseline serologies

– HBcAb, HBsAg for HBcAb+s

– HCV Ab

2nd: Visit 4 samples HBV DNA/HCV RNA

– Real-time PCR assays– COBAS TaqMan system, Roche Diagnostics – LOD 15 IU/ml HBV, 11 IU/ml HCV

3rd: Visit 5 HBcAb, sAg, HCVAb, HBV DNA/HCV RNA– Subjects viremic 2nd timepoint, HBsAg-, HCV Ab- – Potentially had occult infection based on single point

or infected after baseline serologic testing

Methods• Calculated prevalence

OHBV/OHCV 3rd time point• Univariate, multivariate analyses for

associations between OHBV/OHCV and covariates–Demographic–HIV-related, Liver-related –STIs, drug and sexual behavior

845 HBcAb400 cAb-

384 DNA-16 cAb-/DNA+

12 DNA-4 DNA+

445 cAb+

423 sAg-22 sAg+

12 DNA+ 10 DNA- 47 cAb+/DNA+ 376 DNA-

22 DNA+/sAg- 20 DNA-/sAg- 2 DNA+/sAg+

BASELINE

VISIT 4

VISIT 5

OHBVcAb+

Resolved viremia HBsAg+ viremia OHBVcAb-

Resolved viremia

HBsAg+ Viremia HBsAg+ aviremic carrier

Exposure with viremia

Prior exposure without viremia

No exposure

44

OHBV Prevalence 4.7% HIV+ (95% CI 3.1-6.9%)3.1% cohort (95% CI 2.0-4.5%)

OHBV vs. HBsAg+ viremia

OHBV Chronic HBV

*HIV+ 100% 79%

*IDU ever 88% 57%

*HCV Ab+ 88% 43%

*HCV viremia 77% 29%

*all significant p < 0.05

OHBV vs. HBcAb+ aviremia

OHBV HBV-exposed

*HIV+ 100% 69%

*heavy ETOH 23% 11%

*HPV-Ab+ 76% 50%

*Hx gonorrhea 23% 42%

Analysis Restricted to HIV+ women

• OHBV vs. HBcAb+ aviremia:– lower median CD4+ count (205 vs. 326 cells/mm3)

– higher median HIV RNA (36,725 vs. 4,480 c/ml)

– more likely currently inject drugs (54% vs. 32%)

– more likely to drink alcohol heavily (23% vs. 9%) – predictor OHBV: higher HIV VL

• OHBV vs. HBV-unexposed: predictors OHBV

– IDU

– higher HIV viral load

HCV Ab available = 840

459 HCVAb+ 381 HCVAb-

BASELINE

VISIT 4

97 HCV RNA - 362 HCV RNA + 36 HCV RNA + 345 HCV RNA -

HCV Ab+ viremia Exposure with spontaneous clearance viremia

No exposure

33 HCV Ab-/HCV RNA+

24 Ab+, RNA+ 1 Ab-, RNA+ 8 Ab-, RNA-

HCV Ab+ viremia OHCV0.12%

Spontaneous clearance without seroconversion

VISIT 5

Prevalence OHCV

Conclusions

• OHBV is associated with HIV – 4.7% of HIV+ women had OHBV

– May be larger problem for women with poor control of HIV

• OHBV may be parenterally transmitted

• OHCV occurs rarely

Acknowledgements

Cu-Uvin S

This research was funded by a 2007 developmental grant from the Lifespan/Tufts/Brown Center for AIDS Research, P30AI042853.

Klein R, Rompalo A, Schuman P, Gardner L

Stacey Chapman RN

Women of HER Study

Carpenter C

Gholam P

Delong A Wands J