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Background: Hepatitis B virus (HBV) co-infection in human immunodeficiency virus (HIV)-positive individuals increases the risk of overall mortality, especially when HBV DNA levels are high. The role of CD4 + cell counts in this association is poorly defined. We aimed to determine whether HIV-HBV co-infection influences changes in CD4 + cell count before and during antiretroviral therapy and whether it affects mortality risk at levels of CD4 + ., Methods: 2052 HIV-positive participants from Côte d'Ivoire in a randomized-control trial assessing early or deferred ART were included. HBV-status was determined by hepatitis B surface antigen (HBsAg). Changes in CD4 + cell levels were estimated using a mixed-effect linear model. The incidence rates of all-cause mortality were estimated at CD4 + counts ≤350, 351-500, >500/mm 3 and were compared between HBV-status groups as incidence rate ratios (IRR)., Results: At baseline, 190 (9%) were HBsAg-positive [135 (71%) with HBV DNA <2000 IU/mL, 55 (29%) ≥2000 IU/mL]. Follow-up was a median 58 months (IQR = 40-69). Between co-infection groups, there were no differences in CD4 + decline before ART initiation and no differences in CD4 + increase after ART initiation. After adjusting for sex, age, baseline HIV RNA level, and early/deferred ART arm, mortality rates were not significantly different between HBsAg-positive versus HBsAg-negative participants across strata of CD4 + levels. However, HBsAg-positive individuals with HBV-DNA ≥2000 IU/mL versus HBsAg-negative individuals had increased mortality rates at ≤350/mm 3 (adjusted-IRR = 3.82, 95% CI = 1.11-9.70) and 351-500/mm 3 (adjusted-IRR = 4.37, 95% CI = 0.98-13.02), but not >500/mm 3 (adjusted-IRR = 1.07, 95% CI = 0.01-4.91)., Conclusion: Despite no effect of HBV-infection on CD4 + levels, HIV-HBV co-infected individuals with high HBV replication are at higher risk of mortality when CD4 + is <500/mm 3 .

Background: In HIV-HBV-coinfected patients from sub-Saharan Africa, incidence of antiviral resistant HBV-mutations after initiating long-term antiretroviral therapy (ART) has only been evaluated in limited patient populations., Methods: In this nested, prospective cohort study from two randomized controlled trials in Côte d'Ivoire, 168 ART-naive HIV-HBV-coinfected patients, starting lamivudine (LAM, n=82) or tenofovir/emtricitabine (TDF/FTC, n=86) containing ART were included. HBV DNA viral load (VL) was quantified using an in-house assay (detection limit: <12 copies/ml) while pol and preS/S regions of positive samples were sequenced., Results: At ART-initiation, 39 (23.2%) were hepatitis B e antigen-positive, 53 (31.5%) had alanine or aspartate aminotransferase levels >40 IU/ml and 98/100 (98.0%) harboured genotype E. Among the 127 (75.6%) patients with detectable baseline HBV VL (median 4.27 log10 copies/ml, IQR 3.14-7.64), cumulative percentage achieving undetectable HBV DNA was 74.2% for patients undergoing LAM-containing ART and 94.2% for TDF/FTC-containing ART after a median 35.5 months (IQR 24.3-36.5). No baseline antiviral resistance mutations were observed. Among 28/127 (22.1%) patients with low-level persistent viraemia (last HBV VL: between 12 to <10(5) copies/ml), no incident amino acid changes associated with antiviral resistance were observed. Among 11/127 (8.7%) patients with high-level persistent viraemia (last HBV VL: ≥10(5) copies/ml), only two harboured incident LAM-resistance mutations at positions rtV173L+rtL180M+rtM204V with no patient exhibiting TDF/FTC-resistance. Two patients had transaminase flares >120 IU/ml (incidence rate =0.5/100 person-years)., Conclusions: Antiviral resistance, particularly to LAM, was remarkably rare in this cohort of HIV-HBV-coinfected patients. Further research is needed to determine which coinfected populations might benefit from LAM-containing ART with low risk of resistance.

Background: Viral kinetics during therapy provides information on how to individualize treatment. To determine the benefit of assessing positive predictive values (PPVs) and negative predictive values (NPVs) of rapid virological responses (RVRs) and early virological responses (EVRs), on-treatment outcomes in chronic hepatitis C patients were examined., Methods: A total of 408 patients (221 treatment-naive) treated with pegylated interferon-alpha2b and ribavirin were included. Hepatitis C virus (HCV) RNA was measured at baseline, 4 weeks and 12 weeks. RVR was defined as undetectable HCV RNA at 4 weeks and EVR as >/=2 log(10) decrease in HCV RNA at 12 weeks. The additive value of RVR on predicting sustained virological response (SVR) was assessed with receiver operating characteristic (ROC) curves., Results: SVR, RVR and EVR were observed in 46%, 23% and 78% of patients, respectively. PPVs of RVR were 96%, 100% and 100% in treatment-naive patients, relapsers and non-responders, respectively. NPVs of failure to achieve EVR were 97%, 75% and 91%, in treatment-naive patients, relapsers and non-responders, respectively. At 4 weeks, patients with RVR had the highest probability to achieve SVR (odds ratio 44.98 in the entire population and 32.95 in treatment-naive patients). ROC curves showed the area under the ROC curve to be 0.758 versus 0.832 in the entire population and 0.795 versus 0.858 in treatment-naive patients at baseline versus week 4, respectively., Conclusions: RVR is a strong predictor of SVR (PPV>96%) and failure to achieve EVR is a strong predictor of non-SVR (NPV>75%), independent of patients' pretreatment status. Added to baseline characteristics, RVR increased the accuracy to predict SVR. The combination of RVR and EVR provided complementary information, and thus provides a key opportunity to individualize treatment and improve the benefit/risk ratio of therapy.