The humoral and cellular immune responses following booster vaccination with SARS-CoV-2 mRNA in people living with human immunodeficiency virus.

INTRODUCTION: People living with human immunodeficiency virus (PLWH) have higher mortality rates from COVID-19 than those without HIV. Additionally, the seroconversion rate of antibodies following a second dose of SARS-CoV-2 vaccine is lower in PLWH than non-infected individuals, indicating the need for booster vaccination. Here, we evaluated the humoral and cellular immune responses to booster SARS-CoV-2 vaccination in PLWH. METHODS: The dynamics of anti-spike IgG titers and antigen-specific interferon (IFN)-γ levels to SARS-CoV-2 vaccination were assessed over a 6-month period following a third vaccination of 34 PLWH. RESULTS: Antibody titers for humoral immunity were 50 % lower at 24 weeks post-vaccination than those at 12 weeks. However, those at 24 weeks after the booster vaccination were approximately eight times higher than before. Regarding cellular immunity, IFN-γ levels at 24 weeks after the third vaccination were lower than those at 12 weeks, but nearly 90 % of participants maintained a cut-off value of ≥0.15 IU/mL. A comparison between two groups with CD4+ T lymphocytes counts of <500/µL or ≥500/µL exhibited no statistically significant differences in antibody or IFN-γ levels. However, in the group with CD4+ T lymphocyte counts of <500/µL, the rate of IFN-γ above the cut-off value at 24 weeks after the booster vaccination was lower than that of ≥500/µL. CONCLUSION: An immune response is expected in PLWH given successful antiretroviral therapy with booster SARS-CoV-2 vaccination. However, caution should be exercised for cases with low CD4+ T-lymphocyte counts. (240/250 words).

Impact of the PNPLA3 genotype on the risk of hepatocellular carcinoma after hepatitis C virus eradication.

Almost all chronic hepatitis C (CHC) patients can achieve sustained virological response (SVR) with direct-acting antivirals. However, the development of hepatocellular carcinoma (HCC), even after the achievement of SVR, continues to be a serious problem. The aim of this study was to assess the association between host genetic factors and de novo HCC after SVR. This single-center, retrospective study consisted of 442 consecutive CHC patients without a history of HCC who achieved SVR through interferon (IFN)-based and IFN-free therapy. Predictive factors associated with the development of HCC were determined by the Cox proportional hazards model. The single-nucleotide polymorphism (SNP) genotyping data of 223 patients were available for analysis. Of the seven SNPs analyzed in this study, only the patatin-like phospholipase domain containing 3 (PNPLA3) rs738409 GG genotype was significantly, positively associated with the development of de novo HCC after adjusting for age, sex, and fibrosis status (adjusted hazard ratio [aHR] 5.66, p = 0.003). In multivariable analysis, age (aHR 1.05, p = 0.007), advanced fibrosis (aHR 2.69, p = 0.019), α-fetoprotein at post-12 weeks of treatment ≥7.0 ng/ml (aHR 3.85, p = 0.001), and PNPLA3 GG genotype (aHR 3.02, p = 0.004) were extracted as independent predictors of the development of de novo HCC. In conclusion, the PNPLA3 genotype was independently associated with the de novo HCC of CHC patients who achieved SVR. Such detailed knowledge of host genetic factors will be useful for HCC surveillance after HCV elimination.