In recent years, direct-acting antivirals (DAAs) have dramatically improved the sustained virological response (SVR) rates in chronic hepatitis C (CHC) patients with their favorable safety and efficacy. However, there is a lack of data on the long-term prognosis of DAA therapy for CHC patients after achieving SVR in the real world. The aim of this study was to evaluate the long-term clinical prognosis of patients with chronic hepatitis C treated by DAA after achieving SVR. This study was a single-center, retrospective, observational study that included 243 CHC patients who reached SVR after DAA treatment in the Third Affiliated Hospital of Sun Yat-sen University from January 2017 to December 2021, with a median follow-up period (FUP) of 24 months, to assess the long-term prognosis and clinical outcomes of CHC patients who reached SVR by DAA treatment. A total of 243 patients were enrolled in this study, 151 patients were male, the mean age of this study was 46.7 ± 12.3 years old, and 23.0% (n = 56) patients were cirrhosis in the baseline. At the end of follow-up, 9 patients (3.7%) progressed to hepatocellular carcinoma (HCC), and patients with cirrhosis at baseline (n = 5) had a significantly higher risk of HCC compared with noncirrhotic patients (n = 4; OR = 4.485, 95% CI: 1.162–17.318, P = .029); 2.9% patients (n = 7) relapsed at the median FUP of 12 months, and patients with genotype 3b had a significantly higher risk of relapsing than those without genotype 3b (OR = 18.48, P = .002, 95% CI: 2.866–119.169). ALT, AST, and ALB all showed improvement at the end of treatment compared with the baseline, remaining at normal levels during FUP meanwhile. The DAA-induced SVR was durable, with conspicuous improvement in clinical outcomes. Nevertheless, patients, especially patients with cirrhosis, still exist the risk of appearance of HCC after reaching SVR. Therefore, regular surveillance and monitoring is necessary even after patients reached SVR.

Aim: To analyze the prevalence of human immunodeficiency virus type 1 (HIV‐1) drug resistance mutations (DRMs) and compare the therapeutic outcomes of different antiretroviral treatment regimens in newly diagnosed HIV‐1‐infected patients with the V179D/E mutation. Methods: This study included newly diagnosed HIV‐1‐infected individuals in Guangzhou from 2020 to 2024. Peripheral venous blood samples were collected, and viral RNA was extracted. The pol region of HIV genome was amplified and sequenced. Genotypic resistance testing was performed on the obtained pol gene sequences, and the prevalence of DRMs was analyzed. The efficacy of efavirenz (EFV)‐based and non‐EFV‐based regimens in patients with V179D/E mutation was compared using cumulative failure rate curves. Results: Of 740 enrolled patients who underwent baseline resistance testing, 198 (26.76%) harbored DRMs, of whom 59 (7.97%) exhibited pretreatment drug resistance (PDR). The predominant HIV subtypes were CRF07_BC and CRF01_AE. Non‐nucleoside reverse transcriptase inhibitors (NNRTIs) were associated with a DRM prevalence rate of 22.16% ( n = 164/740), with common mutation sites being V179E (45.96%, n = 91/198) and V179D (12.12%, n = 24/198). 58.9% of patients with V179D/E mutations received EFV‐based regimens (EFV group, n = 66/112), while 41.1% (46/112) used integrase strand transfer inhibitors (INSTIs) or protease inhibitors (PIs)‐based regimens (non‐EFV group, n = 46). Besides, the EFV group exhibited significantly higher treatment failure rates than the non‐EFV group ( p = 0.0131). Conclusion: The prevalence of DRMs in newly diagnosed HIV‐1‐infected individuals in Guangzhou associated with NNRTIs is 22.16%, primarily driven by the V179D/E mutation. EFV‐based treatments were associated with higher cumulative virological failure rates in patients with V179D/E mutation.

Eliminating the latent HIV-1 reservoir remains a major barrier to achieving a functional cure. The “block-and-lock” strategy aims to enforce durable transcriptional silencing of proviruses, thereby preventing viral rebound upon interruption of antiretroviral therapy. However, the molecular mechanisms governing stable latency remain incompletely understood. Here, we identify protein kinase C (PKC)-dependent phosphorylation of STAT1 and STAT3 at serine 727 as a previously unrecognized regulatory checkpoint controlling HIV-1 transcriptional reactivation. Pharmacological inhibition of this axis using sorafenib, a clinically approved multi-kinase inhibitor, robustly suppresses HIV-1 reactivation across multiple latency models and promotes the establishment of latency in primary CD4 ⁺ T cells. Mechanistically, sorafenib attenuates phorbol 12-myristate 13-acetate (PMA)-induced activation of the JAK-STAT and PI3K-Akt signaling pathways, and selectively blocks PKC-mediated phosphorylation of STAT1/3 at serine 727 without affecting canonical tyrosine phosphorylation (Y701/Y705). This selective inhibition disrupts transcriptional activation at the HIV-1 long terminal repeat ( LTR ), thereby preventing viral reactivation. Importantly, sorafenib does not induce detectable cytotoxicity or alter activation and exhaustion markers in primary CD4 ⁺ T cells, supporting a favorable safety profile in vitro . Collectively, our findings define a critical role for STAT1/3 Ser727 in the regulation of HIV-1 latency and establish sorafenib as a promising latency-promoting agent for future applications in the development of a functional cure for HIV-1.

Clinical data regarding patients with chronic hepatitis B (CHB) after Omicron BA.5 infection are currently limited. This study aimed to assess the clinical characteristics of patients with CHB and Omicron BA.5 infection in South China. This retrospective study was conducted from January to March 2023 in a cohort of 485 healthy individuals and 553 patients with CHB. Clinical features, encompassing COVID-19-related symptoms, levels of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies, vaccination status, liver functions, and virological markers of hepatitis B virus (HBV) infection were measured. COVID-19-related symptom patterns were similar in both groups, except for fever, which was notably less prevalent (85.4% vs. 90.4%, P = 0.047) among patients with CHB who experienced a significantly shorter duration of fever (median 2.2 (25th–75th percentile, 1.0–3.0) days vs. 2.3 (1.0–3.0) days, P = 0.048) and a shorter time for symptom relief (9.2 (5.0–14.0) vs. 11.1 (5.0–14.0) days, P = 0.015). The levels of SARS-CoV-2 antibodies were comparable between the two groups but increased after booster vaccinations. In patients with CHB, globulin (GLB) and hepatitis B envelope antibody levels were significantly increased after Omicron BA.5 infection, regardless of nucleos(t)ide analog regimens comparing entecavir (ETV) with tenofovir (TFV). Patients with CHB treated with TFV had significantly higher levels of SARS-CoV-2 antibodies than those treated with ETV (1065.1 (346.9–1188.5) COI vs. 765.5 (24.5–1119.1) COI, P = 0.025). No significant exacerbation of COVID-19 symptoms was observed in conjunction with the efficacy of COVID-19 booster vaccinations. There were no notable alterations in liver functions except for GLB. HBV reactivation, as evidenced by increased HBV DNA, was observed among patients with CHB after Omicron BA.5 infection. These changes were not affected by ETV versus TFV administration; however, TFV resulted in a significant increase in SARS-CoV-2 antibody levels. Further studies are required to improve care and therapeutics for patients with CHB who contracted COVID-19.