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Background We evaluated long-term trajectories of circulating hepatitis B virus (HBV) RNA and hepatitis B core–related antigen (HBcrAg) in persons with and without hepatitis B surface antigen (HBsAg) loss during tenofovir therapy in the Swiss HIV Cohort Study. Methods We included 29 persons with HIV with HBsAg loss and 29 matched persons with HIV without HBsAg loss. We compared HBV RNA and HBcrAg decline and assessed the cumulative proportions with undetectable HBV RNA and HBcrAg levels during tenofovir therapy using Kaplan-Meier estimates. Results HBsAg loss occurred after a median of 4 years (IQR, 1–8). All participants with HBsAg loss achieved suppressed HBV DNA and undetectable HBV RNA preceding undetectable quantitative HBsAg levels, whereas 79% achieved negative HBcrAg. In comparison, 79% of participants without HBsAg loss achieved undetectable HBV-RNA and 48% negative HBcrAg. After 2 years of tenofovir therapy, an HBV RNA decline ≥1 log10 copies/mL had 100% sensitivity and 36.4% specificity for HBsAg loss, whereas an HBcrAg decline ≥1 log10 U/mL had 91.0% sensitivity and 64.5% specificity. Conclusions HBV RNA suppression preceded undetectable quantitative HBsAg levels and had high sensitivity but low specificity for HBsAg loss during tenofovir therapy in persons with HIV. HBcrAg remained detectable in approximately 20% of persons with HBsAg loss and 50% of persons without HBsAg loss. [ABSTRACT FROM AUTHOR]

We compared the ability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike-specific antibodies to induce natural killer cell-mediated antibody-dependent cellular cytotoxicity (ADCC) in patients with natural infection and vaccinated persons. Analyzing plasma samples from 39 coronavirus disease 2019 (COVID-19) patients and 11 vaccinated individuals, significant induction of ADCC could be observed over a period of more than 3 months in both vaccinated and recovered individuals. Although plasma antibody concentrations were lower in recovered patients, we found antibodies elicited by natural infection induced a significantly stronger ADCC response compared to those induced by vaccination, which may affect protection conferred by vaccination. [ABSTRACT FROM AUTHOR]

Background: Despite high hepatitis C virus (HCV) treatment rates, HCV incidence among human immunodeficiency virus (HIV)-infected men who have sex with men (HIV-infected MSM) in Germany rose before HCV direct-acting antivirals (DAAs). We model what intervention can achieve the World Health Organization (WHO) elimination target of an 80% reduction in HCV incidence by 2030 among HIV-infected MSM in Berlin.Methods: An HCV transmission model among HIV-diagnosed MSM was calibrated to Berlin (rising HCV incidence and high rates of HCV testing and treatment). We modeled the HCV incidence among HIV-diagnosed MSM in Berlin until 2030 (relative to 2015 WHO baseline) under scenarios of DAA scale-up with or without behavior change (among HIV-diagnosed MSM and/or all MSM).Results: Continuing current treatment rates will marginally reduce the HCV incidence among HIV-diagnosed MSM in Berlin by 2030. Scaling up DAA treatment rates, beginning in 2018, to 100% of newly diagnosed HCV infections within 3 months of diagnosis and 25% each year of previously diagnosed and untreated HCV infections could reduce the HCV incidence by 61% (95% confidence interval, 55.4%-66.7%) by 2030. The WHO target would likely be achieved by combining DAA scale-up with a 40% reduction in HCV transmission among HIV-diagnosed MSM and a 20% reduction among HIV-undiagnosed or HIV-uninfected MSM.Discussion: HCV elimination among HIV-infected MSM in Berlin likely requires combining DAA scale-up with moderately effective behavioral interventions to reduce risk among all MSM. [ABSTRACT FROM AUTHOR]

Recently, we showed chronic hepatitis C to be associated with increased expression of HLA-E and identified peptide hepatitis C virus (HCV) core amino acids 35-44 as a ligand for HLA-E that stabilizes HLA-E expression, favoring inhibition of natural killer cell cytotoxicity. Here we describe HLA-E-restricted recognition of peptide HCV core amino acids 35-44 by CD8+ T cells. Frequency of HLA-E-restricted responses was significantly higher in patients homozygous for the HLAER allele (60% vs 38%; P = .038). Moreover, we found that the HLA-ER allelic variant confers protection against chronic infection with HCV genotypes 2 and 3. Taken together, our data indicate an important immunomodulating function of HLA-E in hepatitis C. [ABSTRACT FROM AUTHOR]

Objective. To assess hepatitis C virus (HCV) antibody prevalence in the Euro SIDA cohort, along with survival, human immunodeficiency virus (HIV)-1 disease progression, virologic response (plasma HIV-1 RNA load of <500 copies/mL), and CD4 cell count recovery by HCV serostatus in patients initiating highly active antiretroviral therapy (HAART). Results. HCV serostatus at or before enrollment was available for 5957 patients; 1960 (33%) and 3997 (67%) were HCV seropositive and seronegative, respectively. No association between an increased incidence of acquired immunodeficiency syndrome-defining illnesses or death and HCV serostatus was seen after adjustment for other prognostic risk factors known at baseline (adjusted incidence rate ratio [IRR], 0.97 [95% confidence interval {CI}, 0.8 1-1.16]). However, there was a large increase in the incidence of liver disease-related deaths in HCV-seropositive patients in adjusted models (IRR, 11.71 [95% CI, 6.42-2 1.34]). Among 2260 patients of known HCV serostatus initiating HAART, after adjustment, there was no significant difference between HCV-seropositive and -seronegative patients with respect to virologic response (relative hazard [RH], 1.13 [95% CI, 0.84-1.51]) and immunologic response, whether measured as a ⩾50% increase (RH, 0.94 [95% CI, 0.77-1.16]) or a ⩾50 cells/μL increase (RH, 0.92 [95% CI, 0.77-1.11]) in CD4 cell count after HAART initiation. Conclusions. HCV serostatus did not affect the risk of HIV-1 disease progression, but the risk of liver disease- related deaths was markedly increased in HCV-seropositive patients. The overall virologic and immunologic responses to HAART were not affected by HCV serostatus. [ABSTRACT FROM AUTHOR]

T cell recruitment to the infected liver is an essential step for the efficient elimination of hepatitis viruses. The surface expression of CC chemokine receptor (CCR) 1, CCR4, and CCR5 on peripheral blood T lymphocytes and their responsiveness to the chemokines macrophage inflammatory proteins (MIP)-lα, MIP-1β, and RANTES (regulated on activation, normally T cell-expressed and secreted) was analyzed in patients with chronic hepatitis C and hepatitis B infection and compared with healthy subjects. Although CCR4 surface expression was not altered, hepatitis C virus (HCV)-infected patients had lower proportions of CD8 T cells with CCR1 and CCR5 surface expression (P < .05). Migration of CD8 T cells in response to MIP-lα, MIP-1β, and RANTES was significantly reduced in HCV-infected patients (P < .05). Intracellular CCR1 and CCR5 protein and messenger RNA levels in peripheral blood T cells did not indicate reduced chemokine receptor biosynthesis in hepatitis C infection. Thus, chronic hepatitis C, but not hepatitis B, infection alters surface expression of distinct CCRs, resulting in lower CC chemokine responsiveness. [ABSTRACT FROM AUTHOR]

Hepatitis C virus infection is a disease that disproportionately affects men more than women. After initial HCV infection, women are more likely to clear the virus spontaneously. Women also have slower rates of liver disease progression than men if they become chronically infected. However, this rate of disease progression changes over time in women. Postmenopausal women have increased rates of fibrosis compared with women of reproductive age because they have lost the protective effects of estrogen. Estradiol and estrogen receptors in the liver protect hepatocytes from oxidative stress, inflammatory injury, and cell death, which all contribute to fibrosis. As a consequence of the overall slower liver disease progression and increased viral clearance in women, the disease burden from HCV infection is found predominantly in men. Although some studies have suggested higher sustained virologic response rates in HCV-infected women receiving dual therapy for HCV infection, this seems to be less important in the direct-acting antiviral era, when response rates for HCV therapy have increased so substantially that baseline demographic factors seem to have less of an effect on overall rates of cure. [ABSTRACT FROM AUTHOR]

The mechanisms involved in HIV-associated natural killer (NK) cell impairment are still incompletely understood. We observed HIV infection to be associated with increased plasma levels of IFABP, a marker for gut epithelial barrier dysfunction, and LBP, a marker for microbial translocation. Both IFABP and LBP plasma concentrations were inversely correlated with NK cell interferon-γ production, suggesting microbial translocation to modulate NK cell functions. Accordingly, we found lipopolysaccharide to have an indirect inhibitory effect on NK cells via triggering monocytes' transforming growth factor-β production. Taken together, our data suggest increased microbial translocation to be involved in HIV-associated NK cell dysfunction., Competing Interests: Potential conflicts of interest . G. J. R. has received travel expenses and honoraria from Gilead. C. B. has received honoraria for consulting or speaking at educational events from AbbVie, Gilead, Janssen, MSD, and ViiV. J. O. has received research funding from Bayer, Biotest, CSL Behring, Octapharma, Pfizer, Swedish Orphan Biovitrum, and Takeda; consultancy, speakers bureau, honoraria, scientific advisory board, and travel expenses from Bayer, Biogen Idec, BioMarin, Biotest, Chugai Pharmaceutical Co, Ltd, CSL Behring, Freeline, Grifols, Novo Nordisk, Octapharma, Pfizer, F. Hoffmann-La Roche Ltd, Sanofi, Spark Therapeutics, Swedish Orphan Biovitrum, and Takeda. J. K. R. has received honoraria for consulting or speaking at educational events from Abivax, Gilead, Janssen, Merck, Theratechnologies, and ViiV. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Human immunodeficiency virus (HIV) infection is associated with impaired natural killer (NK) cell activity, which is only incompletely restored under antiretroviral therapy. Analyzing the bioenergetics profiles of oxygen consumption, we observed that several parameters were significantly reduced in HIV+ NK cells, indicating a mitochondrial defect. Accordingly, we found HIV+ CD56bright NK cells to display a decreased mitochondrial membrane potential and mitochondrial mass. Both parameters were positively correlated with interferon gamma (IFN-γ) production of NK cells. Finally, we demonstrated that stimulation of HIV+ NK cells with MitoTEMPO, a mitochondria-targeting antioxidant, significantly improved IFN-γ production. We identified mitochondrial dysfunction as a mechanism that contributes to impaired NK cell function., Competing Interests: Potential conflicts of interest. G. J. R. has received travel expenses and honoraria from Gilead. C. B. has received honoraria for consulting or speaking at educational events from AbbVie, Gilead, Janssen, MSD, and ViiV. J. K. R. has received honoraria for consulting or speaking at educational events from Abivax, Gilead, Janssen, Merck, Theratechnologies, and ViiV. All other authors report no potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Recently, we showed chronic hepatitis C to be associated with increased expression of HLA-E and identified peptide hepatitis C virus (HCV) core amino acids 35-44 as a ligand for HLA-E that stabilizes HLA-E expression, favoring inhibition of natural killer cell cytotoxicity. Here we describe HLA-E-restricted recognition of peptide HCV core amino acids 35-44 by CD8(+) T cells. Frequency of HLA-E-restricted responses was significantly higher in patients homozygous for the HLA-E(R) allele (60% vs 38%; P = .038). Moreover, we found that the HLA-E(R) allelic variant confers protection against chronic infection with HCV genotypes 2 and 3. Taken together, our data indicate an important immunomodulating function of HLA-E in hepatitis C.