1. 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

2. 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+

3. 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

4. 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

5. 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

6. Methods Study 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

7. Analyzed Data from 3 Timepoints 1 st : Baseline serologies –HBcAb, HBsAg for HBcAb+s –HCV Ab 2 nd : 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 3 rd : Visit 5 HBcAb, sAg, HCVAb, HBV DNA/HCV RNA –Subjects viremic 2 nd timepoint, HBsAg-, HCV Ab- –Potentially had occult infection based on single point or infected after baseline serologic testing

8. Methods Calculated prevalence OHBV/OHCV 3 rd time point Univariate, multivariate analyses for associations between OHBV/OHCV and covariates –Demographic –HIV-related, Liver-related –STIs, drug and sexual behavior

9. 845 HBcAb 400 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 OHBV cAb+ Resolved viremia HBsAg+ viremia OHBV cAb- 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%)

10. OHBV vs. HBsAg+ viremia OHBVChronic HBV *HIV+100%79% *IDU ever88%57% *HCV Ab+88%43% *HCV viremia77%29% *all significant p < 0.05

11. OHBV vs. HBcAb+ aviremia OHBVHBV-exposed *HIV+100%69% *heavy ETOH23%11% *HPV-Ab+76%50% *Hx gonorrhea23%42%

12. 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

13. 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 OHCV 0.12% Spontaneous clearance without seroconversion VISIT 5 Prevalence OHCV

14. 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

15. 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