Chronic HBV infection disproportionately affects people living with HIV, who are often excluded from functional cure studies. This study investigates CD8+ T cell profiles in HBV mono-infection versus HBV/HIV co-infection, examining the impact of long-term therapy on virus-specific responses with the goal of informing therapeutic strategies for immune restoration.

We analysed CD8+ T cell responses in 61 participants (HBV n=20, HBV/HIV n=20, HIV n=21), on suppressive antiviral therapy. We assessed transcriptomic and proteomic profiles, focusing on exhaustion markers alongside virus-specific functional capabilities.

Transcriptomic analysis revealed a distinct signature in co-infection, with upregulation of genes associated with TCR signaling, inhibitory pathways and progenitor-exhausted markers (XCL2, TCF7, PDCD1, IL7R). This gene profile scored highly for a precursor exhausted (Tpex) CD8+ T cell signature, reflecting a "stemness" programme that maintains plasticity despite chronic antigen exposure. Proteomic analysis confirmed higher frequencies of precursor exhausted TCF-1+CD127+PD-1+ CD8+ T cells in co-infection, while HBV mono-infection showed predominance of terminally exhausted ToxhighTCF-1-CD127- cells. These differences correlated with more robust, polyfunctional HBV-specific responses in co-infection against surface and core antigens. Lower HBsAg levels and longer treatment duration in co-infection associated positively with Tpex populations and functional responses and inversely with terminal exhaustion.

Our findings demonstrate that individuals with well-controlled HBV/HIV co-infection maintain more robust CD8+ T cell responses with preserved stem-like properties supporting ongoing antiviral function. These results underscore the benefits of early antiretroviral intervention and the need for tailored immune-modulatory therapies to restore antiviral functionality in these diverse patient populations.

Several studies have reported that combination antiretroviral therapy (cART) enhances the hepatitis B surface antigen (HBsAg) clearance rate in Human Immunodeficiency Virus-1/Hepatitis B Virus (HIV/HBV) coinfected patients, yet the associated immunological characteristics remain unclear.

Global and specific immune phenotypic profiles were examined in 48 patients with HIV/HBV coinfection before cART and at 1-year, and 3-year after cART using flow cytometry. In addition, 61 patients with HBV monoinfection were included for comparison.

HBsAg response (sAg-R) was defined as > 0.5 log decrease within six months of cART initiation, and 16 patients achieved it. Patients with sAg-R (the sAg-R group) exhibited distinct immune phenotypes compared to those of HBsAg-retained patients (the sAg-NR group). Notably, patients with sAg-R had lower CD4+ T cell counts and a higher number of HBcAg-specific T cells. Further, the sAg-R group exhibited upregulation of HLA-DR, Ki67, and PD-1 in CD4+ T cells and heightened HLA-DR and T-bet in CD8+ T cells. However, the sAg-R group had fewer TEMRA cells but more TEM and Th17 cells than those in the sAg-NR group. Expression of various markers, including HLA-DR+CD4+, Ki67+CD4+, PD-1+CD4+, CD38+CD8+, HLA-DR+CD8+, TIM-3+CD8+, HBV-specific CD4+ T cell secreting IFN-γ and IL-2, and specific CD8+ T cell secreting IFN-γ and IL-2, correlated with HBsAg decrease.

The decline in HBsAg levels during cART in HIV/HBV coinfection involves significant alterations in CD4+ and CD8+ T cells phenotypes, offering a novel perspective on a functional HBV cure.

Hepatitis B virus (HBV) has a detrimental effect on human immunodeficiency virus (HIV) natural course, and HBV vaccination is less effective in the HIV infected. We examine the protective effect of dually active antiretroviral therapy (DAART) for HIV/HBV (tenofovir, lamivudine, and emtricitabine) in a large cohort encompassing heterosexuals, men who have sex with men, and intravenous drug users who are HIV infected yet susceptible to HBV, with comprehensive follow-up data about risky behavior and immunological profiles.

We defined an incident HBV infection as the presence of any of HBV serological markers (hepatitis B surface antigen, anti-hepatitis B core antibodies, or HBV DNA) after a negative baseline test result for anti-hepatitis B core antibodies. Patients with positive anti-hepatitis B surface antigen serology were excluded. Cox proportional hazards models were used, with an incident case of HBV infection as the outcome variable.

We analyzed 1716 eligible patients from the Swiss HIV Cohort Study with 177 incident HBV cases. DAART was negatively associated with incident HBV infection (hazard ratio [HR], 0.4; 95% confidence interval [CI], .2-.6). This protective association was robust to adjustment (HR, 0.3; 95% CI, .2-.5) for condomless sex, square-root-transformed CD4 cell count, drug use, and patient demographics. Condomless sex (HR, 1.9; 95% CI, 1.4-2.6), being a man who has sex with men (2.7; 1.7-4.2), and being an intravenous drug user (3.8; 2.4-6.1) were all associated with a higher hazard of contracting HBV.

Our study suggests that DAART, independently of CD4 cell count and risky behavior, has a potentially strong public health impact, including pre-exposure prophylaxis of HBV coinfection in the HIV infected.

Understanding the impact of hepatitis B virus (HBV) in human immunodeficiency virus (HIV) coinfection has been limited by heterogeneity of HIV disease. We evaluated HBV coinfection and HIV-related disease progression in a cohort of HIV seroconverters.

Participants with HIV diagnosis seroconversion window of ≤ 3 years and serologically confirmed HBV infection (HB) status were classified at baseline into 4 HB groups. The risk of clinical AIDS/death in HIV seroconverters was calculated by HB status.

Of 2352 HIV seroconverters, 474 (20%) had resolved HB, 82 (3%) had isolated total antibody to hepatitis B core antigen (HBcAb), and 64 (3%) had chronic HB. Unadjusted rates (95% confidence intervals [CIs]) of clinical AIDS/death for the HB-negative, resolved HB, isolated HBcAb, and chronic HB groups were 2.43 (2.15-2.71); 3.27 (2.71-3.84); 3.75 (2.25-5.25); and 5.41 (3.41-7.42), respectively. The multivariable risk of clinical AIDS/death was significantly higher in the chronic HB group compared to the HB-negative group (hazard ratio [HR], 1.80; 95% CI, 1.20-2.69); while the HRs were increased but nonsignificant for those with resolved HB (HR, 1.17; 95% CI, .94-1.46) and isolated HBcAb (HR, 1.14; 95% CI, .75-1.75).

HBV coinfection has a significant impact on HIV outcomes. The hazard for an AIDS or death event is almost double for those with chronic HB compared, with HIV-monoinfected persons.

To assess the association of hepatitis B virus (HBV) vaccination with risk of HBV infection among HIV-infected patients and HBV infection risk factors among vaccinees.

Observational cohort study.

Participants enrolled from 1986 through 2004, unvaccinated and serologically negative for HBV infection at the time of HIV diagnosis, were followed longitudinally through 2007 for the occurrence of HBV infection. Risk factors for HBV infection were evaluated using time to event methods, including Kaplan-Meier survival curves and Cox proportional hazards models.

During 11 632 person-years of follow-up, the rate of HBV infection was 2.01 (95% CI 1.75-2.27)/100 person-years. Receipt of at least one dose of vaccine was not associated with reduced risk of HBV (unadjusted hazard ratio 0.86, 95% CI 0.7-1.1; adjusted hazard ratio 1.08, 95% CI 0.8-1.4). Receipt of three or more doses of vaccine was also not associated with reduced risk (hazard ratio 0.96; 95% CI 0.56-1.64). Among 409 vaccinees with HBsAb less than 10 IU/l, 46 (11.2%) developed HBV infection compared with 11 of 217 (5.1%) vaccinees with HBsAb > or =10 IU/l (hazard ratio 0.51; 95% CI 0.3-1.0). In participants with initial HBsAb less than 10 IU/l, 16 of 46 (35%) infections were chronic, compared with none of 11 in those with initial HBsAb at least 10 IU/l (P = 0.02).

Overall, HBV vaccination was not associated with reduced risk of HBV infection in our cohort of HIV-infected individuals. However, the small subset of vaccinees with a positive vaccine response may have had reduced HBV infection risk, including chronic disease. Improvements in vaccine delivery and immunogenicity are needed to increase HBV vaccine effectiveness in HIV-infected patients.

Up to one in four patients infected with human immunodeficiency virus type 1 and given antiretroviral therapy (ART) experiences inflammatory or cellular proliferative disease associated with a preexisting opportunistic infection, which may be subclinical. These immune restoration diseases (IRD) appear to result from the restoration of immunocompetence. IRD associated with intracellular pathogens are characterized by cellular immune responses and/or granulomatous inflammation. Mycobacterial and cryptococcal IRD are attributed to a pathological overproduction of Th1 cytokines. Clinicopathological characteristics of IRD associated with viral infections suggest different pathogenic mechanisms. For example, IRD associated with varicella-zoster virus or JC polyomavirus infection correlate with a CD8 T-cell response in the central nervous system. Exacerbations or de novo presentations of hepatitis associated with hepatitis C virus (HCV) infection following ART may also reflect restoration of pathogen-specific immune responses as titers of HCV-reactive antibodies rise in parallel with liver enzymes and plasma markers of T-cell activation. Correlations between immunological parameters assessed in longitudinal sample sets and clinical presentations are required to illuminate the diverse immunological scenarios described collectively as IRD. Here we present salient clinical features and review progress toward understanding their pathogeneses.

To determine the seroprevalence of hepatitis C virus (HCV) and its co-infection with hepatitis B virus (HBV), hepatitis delta agent (HDV) and human immunodeficiency virus (HIV) among liver disease patients of south Tamil Nadu.

A total of 1012 samples comprising 512 clinically diagnosed cases of liver disease patients and 500 apparently healthy age and sex matched individuals were screened for Hepatitis C virus (anti HCV and HCV RNA), Hepatitis B virus (HBsAg), Hepatitis delta agent (anti HDV) and Human immuno virus (antibodies to HIV-1 and HIV-2) using commercially available enzyme linked immunosorbent assay kits. HCV RNA was detected by RT-PCR. Liver function tests like ALT, AST, GGT, ALP, bilirubin and albumin were also studied.

The seroprevalence of HCV was found to be 5.6% among liver disease patients by ELISA. 27/512, 49/512 and 12/512 patients were positive for HIV, HBV & HDV respectively. Co-infection of HCV & HBV was found in 8 patients, with 6 for HCV & HIV and 4 for HCV, HBV & HIV co-infections. Sex-wise analysis showed that HIV, HCV & HBV and HCV & HIV co-infection was high among females whereas for HBV it was high in males. The mean ALT and AST in HCV positive cases were 42.1 ± 8.3 and 49 ± 10.1. In people co-infected with HCV & HBV or HCV & HIV or HCV, HBV & HIV the mean ALT of 58.0 ± 03.16, 56.78 ± 4.401 and 64.37 ± 4.01 respectively.

We strongly recommend routine test of the blood for HCV in addition to HBV and HIV. We also recommend individualized counseling to identify those at risk and testing for those who want it. Improved surveillance and periodic epidemiological studies will have to be undertaken to monitor and prevent these blood-borne viruses.

Factors associated with serologic hepatitis B virus (HBV) outcomes in HIV-infected individuals remain incompletely understood, yet such knowledge may lead to improvements in the prevention and treatment of chronic HBV infection.

HBV-HIV co-infected cohort participants were retrospectively analyzed. HBV serologic outcomes were classified as chronic, resolved, and isolated-HBcAb. Chronic HBV (CHBV) was defined as the presence of HBsAg on two or more occasions at least six months apart. Risk factors for HBV serologic outcome were assessed using logistic regression. Of 2037 participants with HBV infection, 281 (14%) had CHBV. Overall the proportions of HBV infections classified as CHBV were 11%, 16%, and 19% for CD4 cell count strata of > or =500, 200-499, and <200, respectively (p<0.0001). Risk of CHBV was increased for those with HBV infection occurring after HIV diagnosis (OR 2.62; 95% CI 1.78-3.85). This included the subset with CD4 count > or =500 cells/microL where 21% of those with HBV after HIV diagnosis had CHBV compared with 9% for all other cases of HBV infection in this stratum (p = 0.0004). Prior receipt of HAART was associated with improved HBV serologic outcome overall (p = 0.012), and specifically among those with HBV after HIV (p = 0.002). In those with HBV after HIV, HAART was associated with reduced risk of CHBV overall (OR 0.18; 95% CI 0.04-0.79); including reduced risk in the subsets with CD4 > or =350 cells/microL (p<0.001) and CD4 > or =500 cells/microL (p = 0.01) where no cases of CHBV were seen in those with a recent history of HAART use.

Clinical indicators of immunologic status in HIV-infected individuals, such as CD4 cell count, are associated with HBV serologic outcome. These data suggest that immunologic preservation through the increased use of HAART to improve functional anti-HBV immunity, whether by improved access to care or earlier initiation of therapy, would likely improve HBV infection outcomes in HIV-infected individuals.

Following treatment of hepatitis B virus (HBV) monoinfection, HBV-specific T-cell responses increase significantly; however, little is known about the recovery of HBV-specific T-cell responses following HBV-active highly active antiretroviral therapy (HAART) in HIV-HBV coinfected patients. HIV-HBV coinfected patients who were treatment naïve and initiating HBV-active HAART were recruited as part of a prospective cohort study in Thailand and followed for 48 weeks (n = 24). Production of gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) in both HBV- and HIV-specific CD8(+) T cells was quantified using intracellular cytokine staining on whole blood. Following HBV-active HAART, the median (interquartile range) log decline from week 0 to week 48 for HBV DNA was 5.8 log (range, 3.4 to 6.7) IU/ml, and for HIV RNA it was 3.1 (range, 2.9 to 3.5) log copies/ml (P < 0.001 for both). The frequency of HIV Gag-specific CD8(+) T-cell responses significantly decreased (IFN-gamma, P < 0.001; TNF-alpha, P = 0.05). In contrast, there was no significant change in the frequency (IFN-gamma, P = 0.21; TNF-alpha, P = 0.61; and IFN-gamma and TNF-alpha, P = 0.11) or magnitude (IFN-gamma, P = 0.13; TNF-alpha, P = 0.13; and IFN-gamma and TNF-alpha, P = 0.13) of HBV-specific CD8(+) T-cell responses over 48 weeks of HBV-active HAART. Of the 14 individuals who were HBV e antigen (HBeAg) positive, 5/14 (36%) lost HBeAg during the 48 weeks of follow-up. HBV-specific CD8(+) T cells were detected in 4/5 (80%) of patients prior to HBeAg loss. Results from this study show no sustained change in the HBV-specific CD8(+) T-cell response following HBV-active HAART. These findings may have implications for the duration of treatment of HBV in HIV-HBV coinfected patients, particularly in HBeAg-positive disease.

Co-infection of HIV with hepatitis B virus or hepatitis C virus is common. Hepatotoxicity (grade 3 or 4 transaminitis) after highly active antiretroviral therapy occurs more frequently in either hepatitis B virus or hepatitis C virus co-infection. The cause of abnormal alanine aminotransferase following the initiation of highly active antiretroviral therapy is often multifactorial, and may include immune restoration disease. Since the widespread use of highly active antiretroviral therapy, liver disease secondary to viral hepatitis has become one of the most common causes of death in HIV infected individuals. A better understanding of the immunopathogenesis, diagnosis and treatment of hepatitis immune restoration disease is urgently needed, therefore.

Our current understanding of the immunopathogenesis of hepatitis immune restoration disease is limited but it is likely that hepatic damage is secondary to recruitment of both antigen-specific and nonantigen-specific mononuclear cells to the liver, possibly mediated by IFN-gamma. HIV-hepatitis B virus co-infected individuals with low CD4 T-cells and elevated hepatitis B virus DNA and alanine aminotransferase prior to initiation of highly active antiretroviral therapy are at increased risk of hepatitis B virus immune restoration disease. Risk factors for hepatitis C virus immune restoration disease are less well defined. Although clinical deterioration can occur, hepatitis immune restoration disease has also been associated with successful clearance of both hepatitis B virus and hepatitis C virus.

Further randomized clinical trials are needed to develop improved management strategies for hepatitis immune restoration disease.

Coinfection with human immunodeficiency virus-1 (HIV) and hepatitis B virus (HBV) is common; worldwide, an estimated 10% of HIV-infected persons have chronic hepatitis B. Because the incidence of traditional acquired immunodeficiency syndrome-related opportunistic infections has decreased with successful anti-HIV therapy, liver disease has emerged as a leading cause of morbidity and mortality in HIV-infected individuals. HIV infection negatively impacts all phases of the natural history of hepatitis B leading to increased rates of persistent infection, higher HBV DNA levels, lower rates of hepatitis B e antigen loss, increased cirrhosis and liver-related mortality, and increased risk of hepatocellular carcinoma at lower CD4+ T cell counts. The management of hepatitis B in HIV infection is complicated by the dual activity of several nucleoside analogs, the more rapid development of lamivudine-resistant HBV in patients who are HIV-positive, and the paucity of studies in this population. Until further research emerges on the optimal treatment for this population, data from HBV monoinfected persons will need to be extrapolated to the HIV-HBV coinfected population. Further research is also needed to determine the mechanism(s) for the increased liver disease progression and optimal treatment goals.

Following treatment of hepatitis B virus (HBV) infection with nucleos(t)ide reverse transcriptase inhibitors (NRTIs), there is a biphasic clearance of HBV, similar to that seen following treatment of human immunodeficiency virus-1 (HIV-1) and hepatitis C virus. Little is known about the impact of combination NRTIs and HIV-1 coinfection on HBV viral kinetic parameters following the initiation of HBV-active highly active antiretroviral therapy (HAART). HIV-1-HBV coinfected patients (n = 21) were enrolled in a viral kinetics substudy of the Tenofovir in HIV-1-HBV Coinfection study (TICO). TICO was a randomized (1:1:1) trial of tenofovir disoproxil fumarate (TDF, 300 mg) versus lamivudine (LMV, 300 mg) versus TDF/LMV within an efavirenz based HAART regimen initiated in HIV-1-HBV coinfected antiretroviral naïve individuals in Thailand. HBV DNA was measured frequently over the first 56 days. To fit the viral load data, we used a model of HBV kinetics that allows the estimation of treatment effectiveness, viral clearance and infected cell loss. We observed a biphasic decline in HBV DNA in almost all patients. We did not observe any significant differences in HBV viral dynamic parameters between the three treatments groups. Overall, median (interquartile range) HBV treatment effectiveness was 98% (95%-99%), median HBV virion half-life was 1.2 days (0.5-1.4 days), and median infected cell half-life was 7.9 days (6.3-11.0 days). When we compared hepatitis B e antigen (HBeAg)-positive and HBeAg-negative individuals, we found a significantly longer infected cell half-life in HBeAg-positive individuals (6.2 versus 9.0 days, P = 0.02).

HBV viral dynamic parameters are similar following anti-HBV NRTI monotherapy and dual combination therapy in the setting of HIV-1-HBV coinfection. HIV-1 coinfection has minimal effect on HBV viral dynamics, even in the setting of advanced HIV-1-related immunosuppression.

Coinfection with hepatitis B virus (HBV) in human immunodeficiency virus (HIV)-infected patients is common. However, little is known about the natural history of chronic hepatitis B in HIV-infected populations, especially the impact of highly active antiretroviral therapy (HAART) on the outcome of HBV early antigen (HBeAg) and HBV surface antigen (HBsAg) status.

The characteristics of 92 patients coinfected with HIV and HBV were retrospectively assessed before and after HAART and lamivudine treatment to determine the impact of treatment on chronic hepatitis B and factors associated with HBeAg and/or HBsAg seroconversion.

During follow-up, 82 patients received antiretroviral therapy, 79 of whom received HAART. Twenty-eight of the 76 patients who were administered lamivudine therapy developed lamivudine resistance mutations. While receiving antiretroviral therapy, 10 of 59 HBeAg-positive patients developed antibody to HBeAg, 3 of 10 cleared HBsAg, and 2 of 3 developed antibody to HBsAg. Two of 23 HBeAg-negative patients cleared HBsAg and developed antibody to HBsAg. HBeAg and/or HBsAg seroconversion combined with an undetectable HBV DNA level (i.e., an HBV response) correlated with a sustained HIV response (P=.001), shorter duration of antiretroviral therapy (P=.058), and more-severe disease, as evaluated by Centers for Disease Control and Prevention staging (for stage B vs. stage A, P=.029; for stage C vs. stage A, P=.069). For patients with elevated baseline alanine aminotransferase levels, the HBV response correlated significantly with a greater increase in CD4 cell count while receiving HAART.

In HIV-HBV-coinfected patients, HBV response correlated with a sustained HIV response to antiretroviral therapy, usually HAART including lamivudine.

The common occurrence of hepatitis B virus (HBV) infection in patients who carry the human immunodeficiency virus (HIV) demands that both viruses be recognized, evaluated, and treated when appropriate.

We identified 357 HIV- and hepatitis B surface antigen-positive patients who underwent testing from 1999 to 2003; 155 patients who were new to our clinic and who initiated therapy for HIV and HBV coinfection were considered for inclusion in the study. The frequency of HIV testing (to determine HIV load and CD4+ cell count) performed during the first year of therapy was compared with the frequency of HBV measurements (to determine hepatitis B e antigen, antibody to hepatitis B e antigen, and HBV load), abdominal ultrasound examination, and measurement of levels of alpha-fetoprotein in serum.

HBV load data were obtained for only 16% of patients before initiation of antiretroviral therapy (ART), whereas HIV load was determined for 99% of patients before initiation of ART. The total number of HIV load measurements obtained during the first year after ART initiation was 497 (median number of HIV load measurements per patient, 3.0), compared with 85 measurements of HBV load (median number of HBV load measurements per patient, <1; P<.001). The percentage of patients who received any level of HBV monitoring (i.e., tests to determine hepatitis B e antigen, antibody to hepatitis B e antigen, and HBV load) after ART initiation increased from 7% in 1999 to 52% in 2001 (P<.001), whereas the percentage of patients who underwent HIV load testing remained at 80%-90% during the same period.

Health care providers treating patients with HIV infection during the period 1999-2003 infrequently monitored HBV response in coinfected patients, but they systematically monitored HIV response after ART initiation. Improved physician adherence to guidelines that better delineate HBV treatment and monitoring for patients with HIV-HBV coinfection is needed.

Chronic hepatitis B is an important clinical problem often leading to severe complications. In this review, the results obtained in the last few years with the use of current drugs, such as interferon and nucleo(t)side analogues, are summarized and the problems of obtaining a sustained remission, which is only achieved in a small number of patients, are discussed. The new approaches, such as the use of combinations of drugs, to optimize long-term tolerable treatment are also considered.

The immune suppression caused by HIV infection accelerates the course of liver disease caused by chronic hepatitis B virus (HBV) infection. We assessed the outcome of HIV/HBV-coinfected patients exposed to highly active antiretroviral therapy (HAART) including anti-HBV active drugs. Baseline and follow-up plasma HBVDNA and HIV-RNA levels, HBV serological markers, and CD4 counts were longitudinally evaluated in all HBsAg(+) individuals with HIV infection on regular follow-up at an urban HIV reference clinic. Out of 79 HBsAg(+) chronic carriers identified, 39 (50%) were HBeAg(+). Lamivudine (3TC) alone had been received by 37% of patients, while 3TC plus tenofovir (concomitantly or consecutively) had been taken by 58% of them. The median follow-up was of 52 months. Loss of HBeAg or HBsAg occurred in 28% (10/36) and 13% (10/75) of patients, respectively. In multivariate analysis, only undetectable plasma HIV-RNA levels [OR 4.58 (95% CI 1.25-16.78); p = 0.02] and greater CD4 gains on HAART [OR 1.003 (95% CI 1.000-1.006); p = 0.03] were associated with undetectable serum HBV-DNA at the end of follow-up. Anti-HBV active HAART makes it possible to achieve HBsAg clearance, anti-HBe seroconversion, and suppression of HBV replication in a substantial proportion of HBV/HIV-coinfected patients, particularly in those with complete HIV suppression and greater immune recovery. Thus, HBV/HIV-coinfected patients might benefit from an earlier introduction of HAART.

In patients co-infected with HIV and HBV viral load monitoring allows comparison of the efficacy of different antiviral drugs and determination of the initial response to therapy. Usually, the decline in viral load is associated with an improvement in ALT levels and liver histology scores, but some patients show transient elevations in ALT levels due to the restoration of the specific anti-HBV immune response. Analysis of liver histology is useful to determine the improvement of the inflammatory activity of the disease and liver fibrosis, and to make an accurate diagnosis when drug hepatotoxicity is suspected. HBe seroconversion and HBs loss have been described in some patients during anti-HBV therapy with lamivudine, adefovir or tenofovir, indicating that the control of viral replication by these agents may lead to a dramatic suppression of viral load. HBV drug resistant mutants can be diagnosed at an early stage with the monitoring of viral load. Future research directions include the determination of predictive factors of response, the effect of anti-HBV therapy on liver disease severity, the impact of long-term treatment on HBsAg clearance and intrahepatic cccDNA, the impact of HBV drug resistance on the liver disease, the role of cross-resistance testing of HBV strains in patients with HBV treatment failure.

HIV co-infection influences the course and natural history of hepatitis B virus (HBV) infection by impairing the quantity and quality of the innate and adaptive immune response. The rates of spontaneous resolution after acute infection and spontaneous anti-HBe and anti-HBs seroconversions are decreased, and levels of HBV replication are increased in HIV-infected patients. A more rapid progression of liver fibrosis and a higher rate of cirrhosis decompensation (but not hepatocellular carcinoma) have been demonstrated in co-infected patients. The risk of HBV-associated end-stage liver disease and liver-related mortality may be increased by HIV co-infection. Antiretroviral therapy may trigger spontaneous anti-HBe and anti-HBs seroconversion and/or a better immune control of HBV replication by restoring adaptive immunity, but can also increase hepatitis flares. Reactivation of chronic hepatitis B has been observed after suspension of anti-retrovirals with anti-HBV activity or after occurrence of HBV resistance to lamivudine. Future research should focus on: the impact of HIV-induced changes in innate and adaptive immune response and modifications induced by anti-retroviral therapy that may impact on progression of advanced chronic hepatitis B; the association between HBV genotype and clinical course of disease; and the role of occult HBV infection as a co-factor with other causes of liver injury.

Liver disease is a growing problem in HIV-infected persons. In those who are able to take antiretroviral therapy, the forms of liver disease have changed and their relative importance has increased. This review focuses on liver disease in HIV-infected persons, caused by hepatitis C virus, hepatitis B virus, or treatment of HIV infection.

Presented here is the first report of clinical reactivation of hepatitis B virus (HBV) in an HIV-infected patient who previously had anti-HBc as the only serological marker of past infection (anti-HBc alone). Reactivation occurred after lamivudine was removed from the patient's antiretroviral treatment regimen due to lack of virological response. HIV-infected patients frequently present anti-HBc alone, and in some cases this serological profile is associated with occult HBV infection. The current case demonstrates the importance of ruling out the possibility of occult infection in this patient group.

Coinfection with hepatitis B virus (HBV) or hepatitis C virus (HCV) is common in patients with HIV infection. HIV infection and immunosuppression alter the natural history of chronic viral hepatitis, and some patients experience accelerated progression to clinically significant liver disease. Therapies used in the treatment of HBV or HCV monoinfection have been applied to the treatment of HIV-coinfected patients. However, development of viral resistance and lack of virologic response remain significant areas of concern. Timely diagnosis and clinical staging of chronic hepatitis infection are critical in the management of HIV-coinfected patients.

Whether hepatitis B (HBV) coinfection affects outcome in HIV-1-infected patients remains unclear.

To assess the prevalence of HBV (assessed as HBsAg) coinfection and its possible impact on progression to AIDS, all-cause deaths, liver-related deaths and response to highly active antiretroviral therapy (HAART) in the EuroSIDA cohort.

Data on 9802 patients in 72 European HIV centres were analysed. Incidence rates of AIDS, global mortality and liver-related mortality, time to 25% CD4 cell count increase and time to viral load < 400 copies/ml after starting HAART were calculated and compared between HBsAg-positive and HBsAg-negative patients.

HBsAg was found in 498 (8.7%) patients. The incidence of new AIDS diagnosis was similar in HBsAg-positive and HBsAg-negative patients (3.3 and 3.4/100 person-years, respectively) even after adjustment for potential confounders: the incidence rate ratio (IRR) was 0.94 [95% confidence interval (CI), 0.74-1.19; P = 0.61]. The incidences of all-cause and liver-related mortalities were significantly higher in HBsAg-positive subjects (3.7 and 0.7/100 person-years, respectively) compared with HBsAg-negative subjects (2.6 and 0.2/100 person-years, respectively). The adjusted IRR values were 1.53 for global (95% CI, 1.23-1.90; P = 0.0001) and 3.58 for liver-related (95% CI, 2.09-6.16; P < 0.0001) mortality. HBsAg status did not influence viral or immunological responses among the 1679 patients starting HAART.

The prevalence of HBV coinfection was 9% in the EuroSIDA cohort. Chronic HBV infection significantly increased liver-related mortality in HIV-1-infected patients but did not impact on progression to AIDS or on viral and immunological responses to HAART.