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Multicenter Study
. 2012;7(8):e43143.
doi: 10.1371/journal.pone.0043143. Epub 2012 Aug 15.

Hepatitis B surface antigen concentrations in patients with HIV/HBV co-infection

Jerzy Jaroszewicz  1 , Thomas Reiberger, Dirk Meyer-Olson, Stefan Mauss, Martin Vogel, Patrick Ingiliz, Berit Anna Payer, Matthias Stoll, Michael P Manns, Reinhold E Schmidt, Robert Flisiak, Heiner Wedemeyer, Markus Peck-Radosavljevic, Jürgen Rockstroh, Markus Cornberg
Affiliations
Multicenter Study

Hepatitis B surface antigen concentrations in patients with HIV/HBV co-infection

Jerzy Jaroszewicz et al. PLoS One. 2012.

Abstract

HBsAg clearance is associated with clinical cure of chronic hepatitis B virus (HBV) infection. Quantification of HBsAg may help to predict HBsAg clearance during the natural course of HBV infection and during antiviral therapy. Most studies investigating quantitative HBsAg were performed in HBV mono-infected patients. However, the immune status is considered to be important for HBsAg decline and subsequent HBsAg loss. HIV co-infection unfavorably influences the course of chronic hepatitis B. In this cross-sectional study we investigated quantitative HBsAg in 173 HBV/HIV co-infected patients from 6 centers and evaluated the importance of immunodeficiency and antiretroviral therapy. We also compared 46 untreated HIV/HBV infected patients with 46 well-matched HBV mono-infected patients. HBsAg levels correlated with CD4 T-cell count and were higher in patients with more advanced HIV CDC stage. Patients on combination antiretroviral therapy (cART) including nucleos(t)ide analogues active against HBV demonstrated significant lower HBsAg levels compared to untreated patients. Importantly, HBsAg levels were significantly lower in patients who had a stronger increase between nadir CD4 and current CD4 T-cell count during cART. Untreated HIV/HBV patients demonstrated higher HBsAg levels than HBV mono-infected patients despite similar HBV DNA levels. In conclusion, HBsAg decline is dependent on an effective immune status. Restoration of CD4 T-cells during treatment with cART including nucleos(t)ide analogues seems to be important for HBsAg decrease and subsequent HBsAg loss.

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Conflict of interest statement

Competing Interests: The authors have the following conflicts: Lamivudine, GlaxoSmithKline (GSK); Tenofovir and Emtricitabine Gilead; HBsAg test, Abbott, Roche, Siemens. Dr. Jaroszewicz received lecture fees or travel grants from Roche, Gilead and Abbott. Dr. Reiberger received support from Roche (travel grant, lecture fee, grant support), MSD (travel grant, lecture fee) and Gilead (travel grant, grant support). Dr. Meyer-Olson received lecture fees or travel grants from Abbott, Bristol Myers-Squibb, Boehringer Ingelheim, Chugai, Pfizer, Roche. Dr. Mauss received lecture fees Abbott, BMS, Gilead, Janssen, MSD, Roche, advisory board BMS, Gilead, Janssen, Roche. Dr. Vogel has been employed at Janssen-Cilag since June 2011. Dr. Ingiliz has received lecture fees/consultancy fees from Roche, MSD, Gilead, BMS, Abbott, Tibotec. Dr. Payer received support from Roche (grants, lecture fees), MSD (travel grants) and Janssen (travel grants). Dr. Stoll received lecture fees and/or consult fees by Abbott, BMS, Boehringer-Ingelheim, Glaxo-Smith-Kline, ViiV-Healthcare, Roche, Gilead, Janssen-Cilag, Tibotec, Pfizer, and Merck, Sharp & Dohme. Dr. Manns received grants, lectural fees and/or consult fees from GSK, Gilead, Novartis, BMS, and Abbott. Dr. Schmidt received grants lecture fees or consult fees from Gilead, Abbott and Roche. Dr. Flisiak received advisory Board fee from Gilead; Lecture fees from Gilead, Abbott and Roche. Dr. Wedemeyer received grants, lectural fees and/or consult fees from Gilead, Novartis, BMS, and Abbott. Dr. Wedemeyer is also Academic Editor of PLoS ONE. Dr. Peck-Radosavljevic received lecture fee/advisory board from Roche, BMS, Gilead, speaker fees/consulting fees from MSD and grant support from Roche and MSD. Dr. Rockstroh received lecture fees and consult fees from Abbott, BMS, Boehringer, Gilead, GSK, Janssen, Merck, Roche Tibotec, and ViiV. Dr. Cornberg received lecture fees and/or consult fees from GSK, Gilead, Novartis, BMS, Roche, MSD and grant support from Roche and MSD. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials.

Figures

Figure 1
Figure 1. HBsAg levels in overall HIV/HBV cohort.
a) Correlation of HBsAg levels with current CD4 T-cell count in all HIV/HBV co-infected patients. b) HBsAg levels in patients with different CDC stages. c) HBsAg levels in patients with CD4 T-cell counts <200 and ≥200/mm3 and d) in patients with undetectable HBV DNA (lower limit of quantification = LLOD) versus detectable HBV DNA. P-values obtained by Spearman correlation, U-Mann Whitney and Kruskall-Wallis ANOVA tests.
Figure 2
Figure 2. HBsAg levels in HIV/HBV patients receiving cART.
a) Comparison of HBsAg levels in HIV/HBV co-infected patients receiving cART and not undergoing antiviral therapy. Lack of association between HBsAg levels and b) cART duration and c) cART regimen. d) HBsAg levels in patients receiving cART with current CD4 T-cell counts <200 and ≥200/mm3. P-values obtained by Spearman correlation, U-Mann Whitney and Kruskall-Wallis ANOVA tests.
Figure 3
Figure 3. HBsAg levels and CD4 T-cell count dynamics.
a) The correlation between CD4 T-cell count increase on cART (ΔCD4) and HBsAg levels (open circle denote outlier patients with delta CD4 T-cell >600/mm3 but high HBsAg concentrations. 5/6 HBeAg positive, 3/6 (50%) had initially very low nadir CD4 T-cell count (9, 38 and 95 cells/µL). b) Differences in HBsAg levels in HIV/HBV co-infected patients with ΔCD4 T-cell counts <200 and ≥200/mm3 in patients receiving cART and c) in HBeAg positive and HBeAg negative disease. P-values obtained by Spearman correlation and U-Mann Whitney tests.
Figure 4
Figure 4. HBsAg levels in HIV/HBV patients not receiving cART.
Comparison of HBsAg and HBV-DNA levels a) and HBsAg/HBVDNA b) in HIV/HBV co-infected patients not receiving cART with HBV mono-infected individuals without anti-HBV therapy matched for age, gender, HBeAg status and HBV DNA. HBsAg levels in HIV/HBV co-infected patients without cART in c) different CDC stages and d) in patients with CD4 T-cell counts <200 and ≥200/mm3. P-values obtained by U-Mann Whitney and Kruskall-Wallis ANOVA tests.
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