2021年 · 第01卷第02期

Prolonged antiretroviral therapy (ART)-free remission post-treatment has been observed and reported in human immunodeficiency virus-1 (HIV-1) infection. The primary factors for such achievement have been linked to the transcriptional inactivation of HIV-1 DNA and immune recovery. Here, we reported a patient with acute HIV-1 infection who immediately received intensified quadruple ART. At month 9 (M9), an old CFDA-approved immuno-suppressive herbal medicine, Tripterygium Wilfordii Hook F (TwHF), was used in addition to ART. The patient was closely monitored. Virological and immunological tests as well as transcriptome analysis were carried out at each visit. The results showed that TwHF reduced serum IP-10 level and inhibited T cell activation. Both ART and TwHF were discontinued in M24, and levels of peripheral blood HIV-1 RNA and DNA remained suppressed for consecutive 12 months. With transcriptome analysis, we found pattern changes linking immuno-activation and amino acid metabolism with viral suppression and rebound. This indicates that the intentional suppression of immuno-activation is a promising approach for a functional cure of HIV-1 infection.

Hepatitis B virus (HBV) reactivation induced by administration of direct-acting antiviral agents (DAAs) to treat hepatitis C virus (HCV) infection has been reported in previous studies, the subsequent clinical outcomes varied from no symptom to liver failure or death, however, the timing of anti-HBV treatment is controversial. We report the clinical HBV reactivation in a 51 years old female fibrotic patient with chronic HBV-HCV infection during the paritaprevir/ritonavir/ombitasvir and dasabuvir (PrOD) therapy. Her baseline HCV RNA, HBV DNA, alanine aminotransferase (ALT), and liver stiffness measurement levels were 5,560,000 IU/mL, <15 IU/mL, 48 U/L, and 11.8 kPa, respectively. At 8 weeks of PrOD treatment, her HCV RNA, HBV DNA, and ALT levels were <15 IU/mL, 2,880,000 IU/mL, and 837 U/L, respectively, and clinical reactivation was diagnosed. Meanwhile, tenofovir was immediately used for anti-HBV treatment. Fortunately, HBV DNA and ALT were undetectable and normalized after 16 weeks of anti-HBV therapy, and unexpectedly, hepatitis B surface antigen loss occurred at 80 weeks of anti-HBV treatment. This study may extend our understanding of the timing of anti-HBV therapy to prevent potential HBV reactivation during DAAs treatment in HBV-HCV coinfected patients, and proper initiation timing may lead to functional cure of chronic HBV infection.

The coronavirus disease 2019 (COVID-19) can be caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and has led to millions of deaths among more than 100 million infected people around the world according to the declaration from World Health Organization. Dysregulated immune response of both the innate and adaptive immune systems is subsistent on COVID-19 patients, of which the degree are associated with disease severity, lung damage and long term functional disability. Current treatment options have included antiretroviral drugs, anti-inflammatory factors, antibodies, immune checkpoint inhibitors, and convalescent plasma therapy. More recently, mesenchymal stem cell (MSC) therapy has been explored for the management and control of COVID-19, particularly with the aim of preventing or at least mitigating respiratory co-morbidities. Though the safety and efficacy of stem cell therapy have been validated in multiple phase I-III clinical trials, to date, no standardized stem cell preparation, administration dosage or interval, product QA/QC testing, storage, transportation, or disposal protocols have been established. The present paper proposes a systematic methodology that addresses all the foregoing process steps and evaluation criteria for the efficacious and safe administration of MSCs in the treatment of patients infected with COVID-19.

In December 2019, a new coronavirus disease 2019 (COVID-19) emerged and rapidly spread globally, posing a worldwide health emergency. The pathogen causing this pandemic was identified as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). It is well known that SARS-CoV-2 transmits via respiratory droplets and close contact with infected individuals or contaminated items. In addition to these two major transmission routes, other modes of transmission have not been confirmed. Considering that some COVID-19 patients have presented with ocular discomforts and positive SARS-CoV-2 RNA in ocular surfaces, as well as the discovery of the SARS-CoV-2 receptors, angiotensin-converting enzyme 2, and transmembrane protease, serine 2, in the oculus, the ocular surface is now thought to be a possible alternative route of SARS-CoV-2 transmission and a replication site. This review summarizes the evidence connecting COVID-19 with ocular tissues, ocular symptoms during SARS-CoV-2 infection, the potential role of the conjunctiva in SARS-CoV-2 transmission, and the physiopathological mechanisms. Appropriate precautions in ophthalmology departments, including innovative complete and effective patient management plans, protective personal equipment, hand hygiene, and strict personal distance intervals, are essential to effectively minimize the spread of SARS-CoV-2 and control the pandemic.

Human immunodeficiency virus (HIV) has been shown to evolve independently in different anatomical compartments. Characterizing HIV genetic evolution in different tissues and cells provides insights into the mechanisms that maintain the viral reservoir. HIV compartmentalization has been well documented in the semen but rarely in male genital tract (MGT) organs. The precise mechanisms that result in the development of HIV compartmentalization in multiple genitourinary sites have been poorly explored due to the difficulty in accessing these tissues. Based on evidence from lymph nodes and gut tissues, mechanisms that may influence compartmentalization include immune pressures, local concentrations of antiviral drugs, clonal expansion of different cell types and inflammation that alters the cellular microenvironment. We reviewed phylogenetic evidences supporting viral compartmentalization between the blood and multiple genitourinary sites in HIV-infected people. Characterizing distinct viral subpopulations enhances our overall understanding of the HIV reservoir in MGT and could ultimately lead to the development of novel therapies to eradicate the virus in tissues.

Anti-viral therapy with nucleos(t)ide analogs (NUCs) for chronic hepatitis B (CHB) is generally considered to be a long-term treatment. Relevant guidelines issued by Asian Pacific Association for the Study of the Liver, European Association for the Study of the Liver, and American Association for the Study of Liver Diseases have recently proposed requirements and standards for cessation of NUCs, but it remains unclear which proportion of CHB patients on long-term or prolonged treatment of NUCs will relapse after NUCs cessation. Recently, paradoxical increase in loss of hepatitis B surface antigen (HBsAg) with or without the development of anti-hepatitis B surface antibody has been observed in NUCs’ treated CHB patients with cessation of therapy. Hence, it is of great clinical relevance to identify CHB who might have been over-treated with NUCs and might even benefit HBsAg loss or seroconversion with cessation of therapy. To address these issues, our review comprehensively analyzed the data from recent clinical trials in which the antiviral efficacy in the long-term or prolonged treatment of NUCs and/or interferon-α for CHB patients were evaluated. Furthermore, the relevant problems and deficiencies existing in the study design of previous clinical studies were also described. To solve the unmet issues in the field, a prospective study with a large-enough sample size would be required to understand the related virologic and immunological markers that can accurately predict the outcome and prognosis of the CHB patients who stop the NUCs treatment. With the rapid advancement of antiviral drug development for CHB patients, the future ideal regimens should include multiple targets for antiviral drug therapy combined with efficient immune-modulatory therapy, which will help more CHB patients to obtain functional cure with NUCs cessation.