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To understand the problem of persistent Hepatitis B virus (HBV) viraemia in HIV/HBV co-infected patients on HBV-active antiretroviral therapy (ART), we assessed the rate of HBV virological response in patients on HBV-active ART in KwaZulu-Natal, South Africa, and analysed factors associated with persistent HBV viraemia. One hundred and fifty eligible participants with a chronic HBV diagnosis, with or without HIV coinfection, were enrolled and followed up after 6 months. The HBV pol gene was sequenced by next-generation sequencing and mutations were determined using the Stanford HBVseq database. Logistic regression analysis was used to assess factors associated with HBV viraemia at 6-month follow-up. The mean duration of HBV-active ART was 24 months. Thirty-seven of one hundred and six (35%) participants receiving HBV-active ART for longer than 6 months had virological failure. Advanced immunosuppression with CD4+ cell counts <200 cells/μL was independently associated with persistent HBV viraemia, aOR 5.276 (95% CI 1.575–17.670) p = 0.007. A high proportion of patients on HBV-active ART are unsuppressed, which will ultimately have an impact on global elimination goals. Better monitoring should be implemented, especially in HIV-coinfected patients with low CD4+ cell counts and followed by early HBV drug-resistance testing. [ABSTRACT FROM AUTHOR]

Abstract Background Hepatitis B virus (HBV), Human Immunodeficiency virus (HIV) and Tuberculosis (TB) are common infections in South Africa. We utilized the opportunity of care provision for HIV-TB co-infected patients to better understand the relationship between these coinfections, determine the magnitude of the problem, and identify risk factors for HBV infection in HIV infected patients with and without TB in KwaZulu-Natal, South Africa. Methods This retrospective cohort analysis was undertaken in 2018. In-care HIV infected patients were included in the analysis. Results from clinical records were analysed to determine the prevalence, incidence, persistence and factors associated with HBsAg positivity in HIV-infected patients with or without TB co-infection. Results A total of 4292 HIV-infected patients with a mean age of 34.7 years (SD: 8.8) were included. Based on HBsAg positivity, the prevalence of HBV was 8.5% (363/4292) [95% confidence interval (CI): 7.7–9.3] at baseline and 9.4% (95%CI: 8.6–10.3%) at end of follow-up. The HBV incidence rate was 2.1/100 person-years (p-y). Risk of incident HBV infection was two-fold higher among male patients (HR 2.11; 95% CI: 1.14–3.92), while severe immunosuppression was associated with a greater than two-fold higher risk of persistent infection (adjusted risk ratio (RR) 2.54; 95% CI 1.06–6.14; p = 0.004. Additionally, active TB at enrolment was associated with a two-fold higher risk of incident HBV infection (aHR 2.38; 95% CI: 0.77–7.35). Conclusion The provision of HIV care and treatment in high HBV burden settings provide a missed opportunity for HBV screening, immunization and care provision.

We studied the characteristics of immune activation and investigated the underlying mechanisms in patients with human immunodeficiency virus‐1/hepatitis B virus (HIV/HBV) coinfection after receiving HBV‐active antiretroviral therapy. Forty patients with HIV/HBV coinfection, 38 patients with HIV monoinfection and 20 healthy controls were enrolled. CD4+ count, HIV load, HBV load, markers of immune activation and regulatory T‐cell (Treg cell) frequency were assessed and compared between HIV‐monoinfected and HIV/HBV‐coinfected patients at week 0 (baseline), 12, 24, 36 and 48 after the onset of HBV‐active antiretroviral therapy. Before antiretroviral therapy, frequencies of CD4+HLADR+CD38+, CD8+HLADR+CD38+, and Treg cells, and sCD163 and sCD14 levels were significantly higher in both HIV/HBV‐coinfected patients and HIV‐monoinfected patients, compared with healthy controls. Frequencies of CD4+HLADR+CD38+ and CD8+HLADR+CD38+ cells decreased following antiretroviral therapy in both groups. sCD163 levels did not change significantly in both groups and no significant difference was observed between the two groups at each time point during the 48‐week antiretroviral therapy. In week 24, levels of sCD14 and frequencies of Treg cells appeared significantly higher in HIV/HBV‐coinfected patients than in HIV‐monoinfected patients, in which sCD14 levels and Treg cell frequencies declined to those in healthy controls. The Treg cell frequency was consistent with that of sCD14 levels in HIV/HBV‐coinfected patients. Coinfection with HBV significantly increases sCD14 levels in HIV‐infected patients during HBV‐active antiretroviral therapy, which may potentially contribute to liver inflammation. [ABSTRACT FROM AUTHOR]

To understand the problem of persistent Hepatitis B virus (HBV) viraemia in HIV/HBV co-infected patients on HBV-active antiretroviral therapy (ART), we assessed the rate of HBV virological response in patients on HBV-active ART in KwaZulu-Natal, South Africa, and analysed factors associated with persistent HBV viraemia. One hundred and fifty eligible participants with a chronic HBV diagnosis, with or without HIV coinfection, were enrolled and followed up after 6 months. The HBV pol gene was sequenced by next-generation sequencing and mutations were determined using the Stanford HBVseq database. Logistic regression analysis was used to assess factors associated with HBV viraemia at 6-month follow-up. The mean duration of HBV-active ART was 24 months. Thirty-seven of one hundred and six (35%) participants receiving HBV-active ART for longer than 6 months had virological failure. Advanced immunosuppression with CD4+ cell counts p = 0.007. A high proportion of patients on HBV-active ART are unsuppressed, which will ultimately have an impact on global elimination goals. Better monitoring should be implemented, especially in HIV-coinfected patients with low CD4+ cell counts and followed by early HBV drug-resistance testing.

Background The aim of this study was to investigate the impact of anti-HBc (HBcAb) positivity on the progression of liver fibrosis (Fibrosis-4 score >3.25) in the Italian cohort of HIV-infected individuals naïve to antiretroviral treatment (ICONA). Methods All patients with FIB-4 <3.25 at baseline were evaluated prospectively: 6966 people with HIV (PWH) were screened and classified based on hepatitis B virus (HBV) and hepatitis C virus (HCV) serology. Results Patients who were HBcAb+/HCV-/HBs antigen (HBsAg)- and HCV+/HBcAb+/HBsAg- or HBsAg+/HBcAb+/HCV- had CD4+ cell counts below the nadir and significantly higher prevalence of AIDS diagnosis at baseline than the other groups (P <.0001). A Cox regression model adjusted for age, HIV transmission mode, country of birth, and alcohol consumption showed a higher relative risk (HR) of progression to FIB-4 >3.25 in HCV+/HBcAb+/HBsAg- patients (HR, 7.2; 95% CI, 3 8–13.64). Conclusions HBcAb+ contributes to liver damage in HIV+/HCV+/HBcAb+/HBsAg- subjects. A careful monitoring for signs of previous HBV infection is needed in this kind of patients. [ABSTRACT FROM AUTHOR]

Several cohorts have shown that long‐term tenofovir‐containing combination antiretroviral therapy (cART) leads to higher HBsAg seroclearance rates in HIV/HBV coinfected patients vs HBV‐monoinfected patients under tenofovir disoproxil fumarate (TDF)‐based therapy. We have analysed data on determinants of HBsAg loss in a retrospective multicentric cohort of 359 HIV/HBV coinfected patients. Median CD4 T‐cell count at baseline was 359/ul (321‐404), CDC stage was C in 20% (n = 70). Most patients (68%) were ART‐naïve when TDF‐ or tenofovir alafenamide (TAF)‐containing cART was initiated (baseline). After a median follow‐up of 11 years HBsAg loss had occurred in 66/359 (18%) patients. However, patients with stage CDC C (P ≤.001), lower CD4 gain (P =.043) and not receiving TDF/FTC (P =.008) were less likely to lose HBsAg. Long‐term TDF‐containing cART appears to achieve higher rates of HBsAg seroclearance compared to published data for HBV monoinfected subjects. However, late presentation for HIV and poor immune recovery significantly impair HBV seroconversion rates. [ABSTRACT FROM AUTHOR]

Purpose of Review: Limited data exist on the prevalence, determinants, and outcomes of hepatitis delta virus (HDV) infection among HIV/hepatitis B virus (HBV)–coinfected persons. This review provides current evidence on the epidemiology, natural history, and treatment of HDV infection in patients with HIV/HBV coinfection and highlights future research needs. Recent Findings: Cross-sectional studies in Europe, Africa, South America, and Asia show that the prevalence of HDV among HIV/HBV-coinfected patients ranges from 1.2 to 25%. No studies have evaluated the prevalence of HDV infection among HIV/HBV-coinfected patients in the USA. HDV infection increases the risk of hepatic decompensation and hepatocellular carcinoma among HIV/HBV-coinfected patients. HDV treatment remains limited to pegylated interferon-alpha, which results in sustained virologic response in fewer than 25%. Summary: Data on the epidemiology, natural history, and treatment of HDV among HIV/HBV-coinfected persons remain limited. More research is needed to address these knowledge gaps in order to better manage HDV coinfection in HIV/HBV-coinfected patients. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B virus (HBV) is a leading cause of liver failure and hepatocellular carcinoma. Approximately 10% of people with HIV also have HBV and are at higher risk of liver disease progression than in HBV monoinfection. Antivirals, common to HIV and HBV, suppress HBV DNA levels but do not eradicate virus because the transcriptional template, covalently closed circular DNA (cccDNA), is long lived in infected hepatocytes.Methods: Using single-cell laser capture microdissection, we isolated >1100 hepatocytes from 5 HIV/HBV coinfected persons with increasing exposure to HBV antivirals (HB1-HB5; no exposure to >7 years exposure), quantifying cccDNA and pregenomic RNA (pgRNA) in each cell using droplet digital polymerase chain reaction.Results: The proportion of infected hepatocytes decreased with antiviral exposure from 96.4% (HB1) to 29.8% (HB5). Upper cccDNA range and median pgRNA decreased from HB1 to HB5 (P < .05 for both). The amount of pgRNA transcribed per cccDNA also decreased from HB1 to HB5 (P < .05). Cells with inactive pgRNA transcription were enriched from 0% (HB1) to 14.3% (HB5) of infected hepatocytes.Conclusions: cccDNA transcription is reduced in HIV/HBV coinfected people with longer antiviral duration. Understanding HBV transcriptional regulation may be critical to develop a functional cure. [ABSTRACT FROM AUTHOR]

Background: Incomplete hepatitis B virus (HBV) suppression during antiretroviral therapy (ART) in HIV and HBV coinfected patients is common, but underlying factors are not fully elucidated. We hypothesize that genetic factors that influence nucleoside analog pharmacokinetics will affect HBV treatment response. Methods: HIV/HBV coinfected patients on tenofovir disoproxil fumarate/lamivudine (TDF/3TC)-containing ART were enrolled. Selected ABCC4 single nucleotide polymorphisms (SNPs) with known effects on nucleoside pharmacokinetics were genotyped using TaqMan assays. Relationship between ABCC4 SNPs and unsuppressed HBV DNA (HBV DNA ≥20 IU/mL) were examined. Results: Of the 50 participants on TDF/3TC-containing ART for a median (range) of 1.5 (1-7.4) years, 20 (40%) had unsuppressed HBV DNA. Participants with unsuppressed compared with those with suppressed HBV DNA were more likely to have negative HBe antibody, lower body mass index, and lower CD4 count at enrollment. Carriers of ABCC4 rs11568695 (G3724A) variant allele were more likely than noncarriers to have unsuppressed HBV (61.1% vs. 29.0%, P = 0.038). Among 36 patients with suppressed HIV RNA (presumed good ART adherence), ABCC4 rs11568695 variant carriers were more likely than noncarriers to have unsuppressed HBV (58.8% vs. 20.0% P = 0.021). Logistic regression analysis that included genetic and nongenetic factors identified ABCC4 rs11568695 variant allele, body mass index, and male sex as predictors of unsuppressed HBV DNA. Conclusions: We identified a novel association between ABCC4 rs11568695 SNP and poor HBV treatment response. If confirmed in further studies, ABCC4 genotyping could be used to identify individuals who may need intensified HBV therapy. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate whether the presence of anti-hepatitis B (HBV) c antibodies (HBcAb positivity) could influence the control of Human Immunodeficiency Virus (HIV) viremia in patients living with HIV (PLWH) who switch a to two-drug antiretroviral therapy (2DR) containing lamivudine (3TC) (2DR-3TC). A retrospective observational multicenter study was conducted on 166 PLWH switching to the 2DR-3TC-based regimen: 58 HBcAb-positive and 108 HBcAb-negative patients. The HBcAb-positive PLWH group demonstrated a significantly higher percentage of subjects with very low-level viremia at all time points after switching (6th month: p = 0.047; 12th month 34% vs. 27.5%, p = 0.001; 24th month 37% vs. 34.2, p = 0.003 of the HBcAb-positive and HBcAb-negative groups, respectively) and a higher percentage of subjects with detectable HIV RNA greater than 20 copies/mL 12 and 24 months after switching (12 months 32% vs. 11%, p = 0.001; 24 months 37% vs. 13.9%, p = 0.003 of the HBcAb-positive and HBcAb-negative groups, respectively). Logistic regression analysis showed that an increase in age of ten years (OR 2.48 (95% CI 1.58–3.89), p < 0.0001) and the presence of HBcAb positivity (OR 2.7 (5% CI 1.05–6.9), p = 0.038) increased the risk of detectability of HIV RNA by nearly three-fold after switching to 2DR-3TC.

Epidemiology, incidence and prevalence: About 5% of the world’s population has chronic hepatitis B virus (HBV) infection, and nearly 25% of carriers develop chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). The prevalence of chronic HBV infection in human immunodeficiency virus (HIV)-infected individuals is 5%-15%; HIV/HBV coinfected individuals have a higher level of HBV replication, with higher rates of chronicity, reactivation, occult infection, and HCC than individuals with HBV only. The prevalence of HBV genotype A is significantly higher among men who have sex with men (MSM), compared with the rest of the population. Molecular mechanisms of infection, pathology, and symptomatology: HBV replication begins with entry into the hepatocyte. Sodium taurocholate cotransporting polypeptide was identified in 2012 as the entry receptor of HBV. Although chronic hepatitis B develops slowly, HIV/HBV coinfected individuals show more rapid progression to cirrhosis and HCC. Transmission and protection: The most common sources of HBV infection are body fluids. Hepatitis B (HB) vaccination is recommended for all children and adolescents, and all unvaccinated adults at risk for HBV infection (sexually active individuals such as MSM, individuals with occupational risk, and immunosuppressed individuals). Although HB vaccination can prevent clinical infections (hepatitis), it cannot prevent 100% of subclinical infections. Treatment and curability: The goal of treatment is reducing the risk of complications (cirrhosis and HCC). Pegylated interferon alfa and nucleos(t)ide analogues (NAs) are the current treatments for chronic HBV infection. NAs have improved the outcomes of patients with cirrhosis and HCC, and decreased the incidence of acute liver failure.

Worldwide, approximately 10% of all human immunodeficiency virus (HIV)-infected people are also chronically coinfected with hepatitis B virus (HBV). HBV infection has a poor prognosis in HIV-positive people and has been documented by an increased risk of developing chronic HBV infection (CHB), progression to liver fibrosis and end-stage liver disease (ESLD) and evolution of hepatocellular carcinoma (HCC). Furthermore, in HIV patients, HBV-resolved infection is often associated with the appearance of HBV-DNA, which configures occult HBV infection (OBI) as a condition to be explored in coinfected patients. In this narrative review we summarize the main aspects of HBV infection in HIV-positive patients, emphasizing the importance of carefully considering the coinfected patient in the context of therapeutic strategies of antiretroviral therapy.

Background: In the era of combination therapy for human immunodeficiency virus (HIV), liver disease, and hepatocellular carcinoma (HCC) are major causes of death for patients coinfected with HIV and hepatitis B virus (HBV). This study compared HIV provider and hepatologist awareness of and adherence to the American Association for the Study of Liver Diseases (AASLD) practice guidelines for chronic HBV management. The primary endpoint of HIV provider adherence to HCC screening recommendations was compared to that of hepatologists at a large metropolitan academic medical center. Methods: Medical record database searches by ICD-9 codes were used to identify HIV/HBV coinfected (n = 144) and HBV monoinfected (n = 225) patients who were seen at least twice over a 2-year period in outpatient clinics. Adherence to AASLD guidelines was assessed by chart review. Provider awareness was evaluated through a voluntary anonymous survey with knowledge-based questions. Results: Over a 2-year period, only 36.0% of HIV/HBV coinfected patients seen in HIV practices completed HCC screening compared to 81.8% of HBV monoinfected patients in hepatology practices (P < .00001). Similarly, HIV providers less frequently monitored HBV viral load (P < .0001), HBeAg/anti-HBe (P < .00001), HBsAg/anti- HBs (P < .00001) than hepatologists but screened more often for hepatitis A immunity (P = .028). Self-reported adherence and knowledge scores were similar among 19 HIV providers and 16 hepatologists. Conclusions: HIV providers ordered significantly fewer HCC screening and HBV monitoring tests than hepatologists within a single academic medical center. In the setting of increased reliance on quality indicators for care, both patients and providers will benefit from greater adherence to established guidelines. [ABSTRACT FROM AUTHOR]

We investigated the relationship between microbial translocation, immune activation, and liver disease in human immunodeficiency virus (HIV)/hepatitis B virus (HBV) coinfection. Lipopolysaccharide (LPS), soluble CD14, CXCL10, and CCL-2 levels were elevated in patients with HIV/HBV coinfection. Levels of LPS, soluble CD14, and CCL-2 declined following receipt of HBV-active combination antiretroviral therapy (cART), but the CXCL10 level remained elevated. No markers were associated with liver disease severity on liver biopsy (n = 96), but CXCL10, interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor α, and interferon γ (IFN-γ) were all associated with elevated liver enzyme levels during receipt of HBV-active cART. Stimulation of hepatocyte cell lines in vitro with IFN-γ and LPS induced a profound synergistic increase in the production of CXCL10. LPS may contribute to liver disease via stimulating persistent production of CXCL10. [ABSTRACT FROM AUTHOR]

The aim of this retrospective study was the identification of clinically useful viral determinants for the prediction of hepatitis B surface antigen (HBsAg) seroclearance and sustained virological response in hepatitis B virus/human immunodeficiency virus (HBV-/HIV)-coinfected patients receiving HBV-active combined antiretroviral therapy ( cART). Quantification of HBsAg, HBeAg and HBV DNA before and after initiation of HBV-active cART in a cohort of 59 HIV-/HBV-coinfected patients was performed. Calculations of receiver operating characteristics (ROC) and Kaplan-Meier analysis were used for the identification of predictors of HBsAg seroclearance for HBeAg-positive [HBeAg(+); n = 36] and HBeAg-negative [HBeAg(−); n = 23] patients. HBeAg(+) patients with an HBsAg on-treatment decline ≥1 log IU/mL per year achieved higher HBsAg loss rates ( P = 0.0294), whereas the quantification of HBeAg had no predictive value for HBsAg seroclearance. Among HBeAg(−) patients, a pretreatment baseline cut-off level of HBsAg ≤100 IU/mL was highly predictive for HBsAg seroclearance. No significant influence of the HBV genotype on HBsAg seroclearance was observed among the entire cohort. Quantitative determination of HBsAg provides a clinically useful viral parameter for the prediction of HBsAg seroclearance both in HBeAg(+) and HBeAg(−) HIV-/HBV-coinfected patients receiving HBV-active cART. [ABSTRACT FROM AUTHOR]

Abstract: Background: Factors associated with advanced liver disease have been incompletely explored in HIV/HBV coinfected patients. Objectives: To describe liver-related morbidity, mortality, and related risk factors, in HIV/HBV coinfected patients. Study design: We followed-up 107 consecutive HIV/HBV coinfected patients. Clinical, biological and virological data were collected every 3 months. Liver-related mortality and a composite score were used to define advanced liver disease. Results: The patients were mainly sub-Saharan Africans (61%) or Europeans (33%). Forty-four percent of patients had liver biopsy, 78% of patients received lamivudine. Advanced liver disease (ALD) was diagnosed in 19/107 patients during follow-up (mean 4.8 years): 10 extensive fibrosis, 5 cirrhosis, 3 hepatocellular carcinoma resulting from cirrhosis, and 1 fulminant hepatitis following lamivudine withdrawal. Eleven patients died, 4 from HBV-related liver disease. In univariate analysis, male gender, mean HIV and HBV viral loads, and raised AST/ALT transaminases were associated with increased risk of ALD. The strongest associations, in a multivariate model, were mean AST transaminase and cumulated time receiving lamivudine, with a favourable effect. 39% of patients with increased mean AST presented with ALD, versus 7% when normal mean AST (Relative Risk 5.5). Conclusions: During HIV/HBV coinfection, transaminase levels are strongly associated with ALD. Normal mean AST has a high negative predictive value, contrary to previously reported data in HIV/HCV patients. [Copyright &y& Elsevier]

Objectives The aim of the study was to identify and characterize hepatitis B virus (HBV) polymerase gene mutations associated with ongoing HBV replication in HIV/HBV-coinfected individuals receiving tenofovir (TDF). Methods This retrospective cross-sectional study identified 28 HIV/HBV-coinfected individuals who had received TDF for at least 3 months. All patients had samples available while receiving TDF (on-TDF), and 24 also had samples available prior to treatment (pre-TDF). Case records were reviewed to obtain clinical and virological data at the times of sampling (±3 months). The HBV DNA of all samples was amplified using polymerase chain reaction (PCR), and the polymerase region of PCR-positive samples was sequenced and compared with reference HBV data. Results Of the pre-TDF samples, 15 of 24 (63%) were HBV PCR positive. Of the on-TDF samples, four of 28 (14%) were HBV PCR positive (mean time on TDF 13.5 months; range 3–23 months). Lamivudine (3TC)-resistance mutations were detected in three of four (75%) of these viraemic samples. The previously identified putative TDF-resistance mutations, rtA194T+rtL180M+rtM204V, were not detected in any individual. Conclusions Unique mutations in the HBV polymerase gene associated with TDF resistance are rare in HIV/HBV coinfection. 3TC-resistance mutations persist and a significant proportion of patients are HBV PCR positive despite the addition of TDF. [ABSTRACT FROM AUTHOR]

Objectives. A cross-sectional study was conducted to assess the prevalence of human immunodeficiency virus (HIV), hepatitis B virus (HBV), and their coinfection among blood donors at the National Blood Transfusion Center in Bamako, Mali, from November 2001 to July 2002. Methods. Enzyme-linked immunosorbent assay techniques with reagents from Bio-Rad (France) were used to test the blood samples. Results. 11 592 blood donors were tested for HIV and HBV surface antigens. The prevalence of HIV was 4.5% and the prevalence of HBV was 14.9%. The HIV/HBV coinfection rate was only 1.13% in this population. Conclusion. The coinfection rate was unexpectedly low in this blood donor population where monoinfection with HIV or HBV prevalence was high. [ABSTRACT FROM AUTHOR]

As therapy for human immunodeficiency virus (HIV) infection evolves, optimizing hepatitis B virus (HBV) treatment and identifying factors that impact its response in the HIV/HBV-coinfected population is critical. We identified retrospectively 45 HBV/HIV-coinfected patients with detectable HBV DNA by the Bayer VERSANT® HBV 3.0 bDNA assay (limit of quantification 2000 copies/mL) at baseline and/or year 1 of therapy. Patients were divided into three groups based on the active HBV agent in their antiretroviral regimen: group 1 ( n = 15) received lamivudine; group 2 ( n = 10), lamivudine plus tenofovir and group 3 ( n = 20), lamivudine followed by lamivudine plus tenofovir. HBV genotypes and resistance profiles were determined by the Bayer Trugene® HBV 1.0 assay. More patients in group 2 achieved HBV DNA suppression below 2000 copies/mL (80%), loss of HBe antigen (HBeAg) (40%) and loss of HBeAg and gain of anti-HBe (20%) than did patients in group 1 or 3. More patients with HBV genotype A, achieved HBV DNA suppression <2000 copies/mL than did patients with non-A genotypes [74% (26/35) vs 20% (2/10)], respectively ( P = 0.003). Risk for virological nonresponse was significant in those with non-A genotypes [odds ratio (OR) 11.1; 95% CI: 2.0–50], previous HIV therapy (OR 6.5; 95% CI: 1.2–35) and <90% compliance (OR 3.7; 95% CI: 0.99–14.3). Simultaneous therapy with lamivudine/tenofovir suppresses HBV DNA more effectively than lamivudine or tenofovir added to lamivudine. More patients infected with HBV genotype A responded than the non-A patients, regardless of therapeutic regimen, compliance or prior HIV therapy. [ABSTRACT FROM AUTHOR]

Direct-acting antivirals (DAA) have revolutionized the treatment of patients with chronic hepatitis C virus (HCV) infection, possibly leading to HCV elimination by 2030 as endorsed by the World Health Organization (WHO). However, some patients belonging to the so-called unique or special populations are referred to as difficult-to-treat due to unreached sustained virological response, potential drug side effects or interactions or co-morbidities. Several years after the DAA introduction and on the basis of excellent findings in terms of efficacy and safety, some doubts arise around the exact meaning of the special population designation and whether this group of patients actually exists. The aim of this review is to discuss and analyze current evidence on the management and treatment of the so-called "unique populations". We placed particular emphasis on patients with decompensated cirrhosis, chronic kidney disease (CKD), coinfections, rare genotypes, and previous treatment failure, in order to provide physicians with an updated overview of the actual problems and needs in the current scenario. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate whether the presence of anti-hepatitis B (HBV) c antibodies (HBcAb positivity) could influence the control of Human Immunodeficiency Virus (HIV) viremia in patients living with HIV (PLWH) who switch a to two-drug antiretroviral therapy (2DR) containing lamivudine (3TC) (2DR-3TC). A retrospective observational multicenter study was conducted on 166 PLWH switching to the 2DR-3TC-based regimen: 58 HBcAb-positive and 108 HBcAb-negative patients. The HBcAb-positive PLWH group demonstrated a significantly higher percentage of subjects with very low-level viremia at all time points after switching (6th month: <31% vs. 17.6%, p = 0.047; 12th month 34% vs. 27.5%, p = 0.001; 24th month 37% vs. 34.2, p = 0.003 of the HBcAb-positive and HBcAb-negative groups, respectively) and a higher percentage of subjects with detectable HIV RNA greater than 20 copies/mL 12 and 24 months after switching (12 months 32% vs. 11%, p = 0.001; 24 months 37% vs. 13.9%, p = 0.003 of the HBcAb-positive and HBcAb-negative groups, respectively). Logistic regression analysis showed that an increase in age of ten years (OR 2.48 (95% CI 1.58–3.89), p < 0.0001) and the presence of HBcAb positivity (OR 2.7 (5% CI 1.05–6.9), p = 0.038) increased the risk of detectability of HIV RNA by nearly three-fold after switching to 2DR-3TC. [ABSTRACT FROM AUTHOR]

Background: Chronic immune activation is one of the most widely recognized hallmarks of HIV infection. T-cells that express CD38+ and HLA-DR+ show poor proliferative potential, signal transduction, and increased apoptotic potential. This affects HIV pathogenesis and its outcome and further complicates with a coinfection like HBV., Methods: Study Design: cross-sectional. Blood samples were collected and analyzed for virological markers using ELISA for HBeAg and RT-PCR for HIV&HBV Viral load. Chronic immune activation markers of CD8+ and CD4+ T cells were measured by Flow cytometry for both HIV and HBV., Results: There was a significant increase in HBV replication shown by higher HBV DNA (p=0.002), a higher proportion of HBeAg (p=0.0049), and lower CD4 counts (p=0.04) among HIV/HBV coinfected individuals, compared to the monoinfected groups. The frequencies of CD4+ CD38+ HLA-DR+ and CD8+ CD38+ HLA-DR+ in the HIV/HBV coinfection were significantly higher than HBV monoinfected group (P< 0.0001) and in the HIV monoinfected group (P < 0.0001). The Liver fibrosis score APRI and FIB-4, were higher in the coinfected group compared with HBV monoinfected group (0.67 vs. 0.25, p = 0.0085; 3.48 vs. 0.98, p = 0.0026) respectively. The cytokine levels of IL-17, Fas-L,TNF -α, IL-10, IL-2 and Granzyme B were also measured and compared among the study groups., Conclusion: Our data suggest that HIV probably influences immune activation of CD4+ and CD8+ T cells and this may play a significant role in accelerating the disease outcome among HIV/HBV coinfected individuals., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Several cohorts have shown that long-term tenofovir-containing combination antiretroviral therapy (cART) leads to higher HBsAg seroclearance rates in HIV/HBV coinfected patients vs HBV-monoinfected patients under tenofovir disoproxil fumarate (TDF)-based therapy. We have analysed data on determinants of HBsAg loss in a retrospective multicentric cohort of 359 HIV/HBV coinfected patients. Median CD4 T-cell count at baseline was 359/ul (321-404), CDC stage was C in 20% (n = 70). Most patients (68%) were ART-naïve when TDF- or tenofovir alafenamide (TAF)-containing cART was initiated (baseline). After a median follow-up of 11 years HBsAg loss had occurred in 66/359 (18%) patients. However, patients with stage CDC C (P ≤ .001), lower CD4 gain (P = .043) and not receiving TDF/FTC (P = .008) were less likely to lose HBsAg. Long-term TDF-containing cART appears to achieve higher rates of HBsAg seroclearance compared to published data for HBV monoinfected subjects. However, late presentation for HIV and poor immune recovery significantly impair HBV seroconversion rates., (© 2020 The Authors. Liver International published by John Wiley & Sons Ltd.)

Background: The aim of this study was to investigate the impact of anti-HBc (HBcAb) positivity on the progression of liver fibrosis (Fibrosis-4 score >3.25) in the Italian cohort of HIV-infected individuals naïve to antiretroviral treatment (ICONA)., Methods: All patients with FIB-4 <3.25 at baseline were evaluated prospectively: 6966 people with HIV (PWH) were screened and classified based on hepatitis B virus (HBV) and hepatitis C virus (HCV) serology., Results: Patients who were HBcAb+/HCV-/HBs antigen (HBsAg)- and HCV+/HBcAb+/HBsAg- or HBsAg+/HBcAb+/HCV- had CD4+ cell counts below the nadir and significantly higher prevalence of AIDS diagnosis at baseline than the other groups ( P < .0001). A Cox regression model adjusted for age, HIV transmission mode, country of birth, and alcohol consumption showed a higher relative risk (HR) of progression to FIB-4 >3.25 in HCV+/HBcAb+/HBsAg- patients (HR, 7.2; 95% CI, 3 8-13.64)., Conclusions: HBcAb+ contributes to liver damage in HIV+/HCV+/HBcAb+/HBsAg- subjects. A careful monitoring for signs of previous HBV infection is needed in this kind of patients., (© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Worldwide, approximately 10% of all human immunodeficiency virus (HIV)-infected people are also chronically coinfected with hepatitis B virus (HBV). HBV infection has a poor prognosis in HIV-positive people and has been documented by an increased risk of developing chronic HBV infection (CHB), progression to liver fibrosis and end-stage liver disease (ESLD) and evolution of hepatocellular carcinoma (HCC). Furthermore, in HIV patients, HBV-resolved infection is often associated with the appearance of HBV-DNA, which configures occult HBV infection (OBI) as a condition to be explored in coinfected patients. In this narrative review we summarize the main aspects of HBV infection in HIV-positive patients, emphasizing the importance of carefully considering the coinfected patient in the context of therapeutic strategies of antiretroviral therapy. [ABSTRACT FROM AUTHOR]

Background:  There is limited information on antiviral therapy for hepatitis B virus (HBV) infection among pregnant women coinfected with human immunodeficiency virus (HIV) and HBV., Methods:  A phase 2 randomized, controlled trial of a regimen containing tenofovir (TDF)/lamivudine (3TC) and a regimen containing 3TC in HIV/HBV-coinfected pregnant women in China. The HBV virological response was compared in study arms., Results:  The median decline in the HBV DNA level was 2.60 log 10 copies/mL in the TDF/3TC arm and 2.24 log 10 copies/mL in the 3TC arm (P = .41). All women achieved HBV DNA levels of <6 log 10 copies/mL at delivery., Conclusions:  Initiation of either regimen led to achievement of HBV DNA levels below the threshold associated with perinatal HBV transmission., Clinical Trials Registration:  NCT01125696., (Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Epidemiology: incidence and prevalence: About 5% of the world's population has chronic hepatitis B virus (HBV) infection, and nearly 25% of carriers develop chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). The prevalence of chronic HBV infection in human immunodeficiency virus (HIV)-infected individuals is 5%-15%; HIV/HBV coinfected individuals have a higher level of HBV replication, with higher rates of chronicity, reactivation, occult infection, and HCC than individuals with HBV only. The prevalence of HBV genotype A is significantly higher among men who have sex with men (MSM), compared with the rest of the population. Molecular mechanisms of infection, pathology, and symptomatology: HBV replication begins with entry into the hepatocyte. Sodium taurocholate cotransporting polypeptide was identified in 2012 as the entry receptor of HBV. Although chronic hepatitis B develops slowly, HIV/HBV coinfected individuals show more rapid progression to cirrhosis and HCC. Transmission and protection: The most common sources of HBV infection are body fluids. Hepatitis B (HB) vaccination is recommended for all children and adolescents, and all unvaccinated adults at risk for HBV infection (sexually active individuals such as MSM, individuals with occupational risk, and immunosuppressed individuals). Although HB vaccination can prevent clinical infections (hepatitis), it cannot prevent 100% of subclinical infections. Treatment and curability: The goal of treatment is reducing the risk of complications (cirrhosis and HCC). Pegylated interferon alfa and nucleos(t)ide analogues (NAs) are the current treatments for chronic HBV infection. NAs have improved the outcomes of patients with cirrhosis and HCC, and decreased the incidence of acute liver failure., Competing Interests: Conflict of interest: Potential conflicts of interest: none reported.

Background.  Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) coinfection has emerged as an important cause of morbidity and mortality. We determined the response to Truvada-based first-line combination antiretroviral therapy (cART) in HIV/HBV-coinfected verus HIV-monoinfected patients in Botswana. Methods.  Hepatitis B virus surface antigen (HBsAg), HBV e antigen (HBeAg), and HBV deoxyribonucleic acid (DNA) load were determined from baseline and follow-up visits in a longitudinal cART cohort of Truvada-based regimen. We assessed predictors of HBV serostatus and viral suppression (undetectable HBV DNA) using logistic regression techniques. Results.  Of 300 participants, 28 were HBsAg positive, giving an HIV/HBV prevalence of 9.3% (95% confidence interval [CI], 6.3-13.2), and 5 of these, 17.9% (95% CI, 6.1-36.9), were HBeAg positive. There was a reduced CD4 + T-cell gain in HIV/HBV-coinfected compared with HIV-monoinfected patients. Hepatitis B virus surface antigen and HBeAg loss was 38% and 60%, respectively, at 24 months post-cART initiation. The HBV DNA suppression rates increased with time on cART from 54% to 75% in 6 and 24 months, respectively. Conclusions.  Human immunodeficiency virus/HBV coinfection negatively affected immunologic recovery compared with HIV-1C monoinfection. Hepatitis B virus screening before cART initiation could help improve HBV/HIV treatment outcomes and help determine treatment options when there is a need to switch regimens.