Title: Occult hepatitis B virus HBV and hepatitis C virus HCV viremia in women with and atrisk for HIVAIDS
1Occult 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
2Background
- 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
3Limits 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
4Objectives
- 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
- Examine demographic, behavioral, serological
characteristics associated with OHBV and OHCV -
5Methods
- 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
6Methods
- 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
7Analyzed Data from 3 Timepoints
- 1st Baseline serologies
- HBcAb, HBsAg for HBcAbs
- 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
8Methods
- 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
9OHBV Prevalence
4.7 HIV (95 CI 3.1-6.9) 3.1 cohort (95 CI
2.0-4.5)
BASELINE
845 HBcAb
400 cAb-
445 cAb
423 sAg-
22 sAg
VISIT 4
16 cAb-/DNA
12 DNA
10 DNA-
47 cAb/DNA
376 DNA-
384 DNA-
HBsAg aviremic carrier
Exposure with viremia
Prior exposure without viremia
No exposure
HBsAg Viremia
44
VISIT 5
20 DNA-/sAg-
2 DNA/sAg
12 DNA-
4 DNA
22 DNA/sAg-
HBsAg viremia
Resolved viremia
Resolved viremia
OHBV cAb-
OHBV cAb
10OHBV vs. HBsAg viremia
all significant p lt 0.05
11OHBV vs. HBcAb aviremia
12Analysis 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
13Prevalence OHCV
HCV Ab available 840
BASELINE
459 HCVAb
381 HCVAb-
VISIT 4
36 HCV RNA
345 HCV RNA -
97 HCV RNA -
362 HCV RNA
Exposure with spontaneous clearance viremia
HCV Ab viremia
No exposure
33 HCV Ab-/HCV RNA
VISIT 5
24 Ab, RNA
1 Ab-, RNA
8 Ab-, RNA-
Spontaneous clearance
without seroconversion
HCV Ab viremia
OHCV 0.12
14Conclusions
- 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
15Acknowledgements
Delong A
Wands J
Cu-Uvin S
Gholam P
Carpenter C
Klein R, Rompalo A, Schuman P, Gardner L Stacey
Chapman RN Women of HER Study
This research was funded by a 2007 developmental
grant from the Lifespan/Tufts/Brown Center for
AIDS Research, P30AI042853.