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Introduction Human noroviruses (HuNoVs) are non-enveloped, positive-sense, single-stranded RNA viruses. They are classified into 10 genogroups and further subdivided into genotypes, of which 5 genotypes encompass over 40 genotypes that [...], Human noroviruses cause significant morbidity and mortality worldwide, but lack approved antivirals or vaccines to treat or prevent infections. The recent development of two cell culture systems in human transformed B cells (BJABs) and non-transformed human intestinal enteroid cultures overcomes a main limitation in identifying molecules with anti-norovirus activities. Lactoferrin is an iron-binding glycoprotein found in the milk of most mammals, with broad spectrum antimicrobial activities, including against the related murine norovirus in cell culture. In a Japanese clinical trial, ingestion of lactoferrin reduced the incidence of infectious gastroenteritis in the participants. Because human noroviruses were the most common cause of gastroenteritis in Japan during the clinical trial period, we sought to determine whether lactoferrin could inhibit infection with human norovirus. Our study, using a B cell culture model, demonstrates that lactoferrin reduces human norovirus infection. The mechanism of antiviral action is likely indirect and may involve the induction of innate interferon responses. Therefore, future studies are warranted to test the antiviral efficacy of lactoferrin against human norovirus infection in patients. Key words: human norovirus, lactoferrin, interferon, human B cell. Les norovirus humains sont responsables d'une morbidite et d'une mortalite importantes a travers le monde, mais il n'existe pas d'antiviraux ou de vaccins approuves pour traiter ou prevenir les infections. Le developpement recent de deux systemes de cultures cellulaires consistant en cellules B humaines transformees (BJAB) et en enteroides intestinaux humains non transformes permet de surmonter une des principales limites a l'identification de molecules possedant des activites anti-norovirus. La lactoferrine est une glycoproteine qui lie le fer et que l'on trouve dans le lait de la plupart des mammiferes. Elle possede un large spectre d'activites antimicrobiennes, y compris en culture cellulaire, contre le norovirus murin apparente. Son ingestion reduisait aussi l'incidence de gastroenterites infectieuses chez des participants a une etude clinique au Japon. Puisque les norovirus humains constituaient la cause la plus frequente de gastroenterite au Japon au cours de la periode couverte par l'etude clinique, les auteurs desiraient determiner si la lactoferrine pouvait inhiber l'infection au norovirus humain. Leur etude demontre que la lactoferrine reduit l'infection au norovirus humain dans le modele de cellules B en culture. Le mecanisme d'action antivirale est probablement indirect et peut impliquer l'induction de reponses innees a l'interferon. Consequemment, des etudes futures visant a tester l'efficacite antivirale de la lactoferrine contre l'infection aux norovirus humains chez les patients sont justifiees. [Traduit par la Redaction] Mots-cles : norovirus humain, lactoferrine, interferon, cellule B humaine.

Introduction SARS-CoV-2 is the etiological agent of coronavirus disease 19 (COVID-19) and belongs to the same group of RNA viruses that caused SARS and Middle East respiratory syndrome (MERS) in [...], BACKGROUND. Coronavirus disease 19 (COVID-19) is an emerging infectious disease caused by SARS-CoV-2. Antiviral immune response is crucial to achieve pathogen clearance; however, in some patients an excessive and aberrant host immune response can lead to an acute respiratory distress syndrome. The comprehension of the mechanisms that regulate pathogen elimination, immunity, and pathology is essential to better characterize disease progression and widen the spectrum of therapeutic options. METHODS. We performed a flow cytometric characterization of immune cell subsets from 30 patients with COVID-19 and correlated these data with clinical outcomes. RESULTS. Patients with COVID-19 showed decreased numbers of circulating T, B, and NK cells and exhibited a skewing of [CD8.sup.+] T cells toward a terminally differentiated/senescent phenotype. In agreement, [CD4.sup.+] T and [CD8.sup.+] T, but also NK cells, displayed reduced antiviral cytokine production capability. Moreover, a reduced cytotoxic potential was identified in patients with COVID-19, particularly in those who required intensive care. The latter group of patients also showed increased serum IL-6 levels that inversely correlated to the frequency of granzyme A-expressing NK cells. Off-label treatment with tocilizumab restored the cytotoxic potential of NK cells. CONCLUSION. The association between IL-6 serum levels and the impairment of cytotoxic activity suggests the possibility that targeting this cytokine may restore antiviral mechanisms. FUNDING. This study was supported by funds from the Department of Experimental and Clinical Medicine of University of Florence (the ex-60% fund and the 'Excellence Departments 2018-2022 Project') derived from Ministero dell'Istruzione, dell'Universita e della Ricerca (Italy).

Adenoviruses (Ads) cause a wide array of end-organ and disseminated diseases in severely immunosuppressed patients. For example, [approximately equal to] 20% of pediatric allogeneic hematopoietic stem cell transplant recipients develop disseminated Ad infection, and the disease proves fatal in as many as 50-80% of these patients. Ad infections are a serious problem for solid-organ transplant recipients and AIDS patients as well. Unfortunately, there are no antiviral drugs approved specifically to treat these infections. A suitable animal model that is permissive for Ad replication would help in the discovery process. Here we identify an animal model to study Ad pathogenesis and the efficacy of antiviral compounds. We show that human serotype 5 Ad (ADS) causes severe systemic disease in immunosuppressed Syrian hamsters that is similar to that seen in immunocompromised patients. We also demonstrate that hexadecyloxypropyl-cidofovir (CMX001) rescues the hamsters from a lethal challenge with Ad5. The antiviral drug provided protection both prophylactically and when given up to 2 days after i.v. exposure to Ad5. CMX001 acts by reducing Ad replication in key target organs. Thus, the immunosuppressed Syrian hamster is a powerful model to evaluate anti-Ad drugs, and its use can facilitate the entry of drugs such as CMX001 into clinical trials. antivirals | hamster

A study conducted to compare measures of adherence to antiretroviral therapy (ART) in HIV-positive adults receiving free treatment from a public hospital in Malawi recommend a requirement of improved methods to detect nonadherence in developing countries and validation of MC data with drug levels and virologic outcome.

ROTAVIRUS IS THE leading cause of severe acute gastroenteritis in children under the age of 5 years worldwide. (1) In the United States, rotavirus gastroenteritis (RVGE) rarely causes mortality, but [...], BACKGROUND. Rotavirus is the leading cause of dehydrating acute gastroenteritis in infants worldwide. Previous studies of a live pentavalent human-bovine reassortant rotavirus vaccine have shown it to be efficacious across a range of potencies. OBJECTIVE. Our goal was to evaluate the efficacy, immunogenicity, and safety of pentavalent rotavirus vaccine at the end of shelf life in healthy infants. PATIENTS AND METHODS. During 2002-2004, 1312 healthy infants ~6 to 12 weeks old from the United States (47%) and Finland (53%) were randomly assigned to receive 3 oral doses of vaccine (vaccine at ~1.1 x [10.sup.7] infectious U per dose) or placebo ~4 to 10 weeks apart. Infants were to be followed for acute gastroenteritis through 1 rotavirus season after vaccination and for adverse events postvaccination. RESULTS. Three doses of pentavalent rotavirus vaccine at the end of shelf life demonstrated efficacy against rotavirus gastroenteritis caused by human G-serotypes included in the vaccine (G1-G4). Efficacy against severe rotavirus gastroenteritis was 100%, and efficacy against any rotavirus gastroenteritis regardless of severity was 72.5%. A threefold rise in G1 serum neutralizing was observed in 57% and in anti-rotavirus immunoglobulin A in 96% of pentavalent rotavirus vaccine recipients. No statistically significant increase in vomiting, diarrhea, or irritability was observed among pentavalent rotavirus vaccine recipients compared with placebo recipients within the 7-day period from each dose. A statistically significant increase in fevers (≥100.5°F, rectal equivalent) was observed among pentavalent rotavirus vaccine recipients compared with placebo recipients after dose 1. CONCLUSIONS. This pentavalent human-bovine rotavirus vaccine was generally well tolerated, efficacious, and immunogenic at the end of shelf life. Key Words gastroenteritis, rotavirus vaccine, rotavirus, safety, efficacy

Results of a study on treatment of HIV/AIDS with antiretroviral therapy indicate that continuous antiretroviral treatment is essential for a positive outcome. The main focus of attention now should be on making antiretroviral therapy cheaper and less toxic.

A study was conducted to establish whether continuous antiretroviral therapy is more effective as a mode of treatment for HIV/AIDS than episodic use of antiretroviral therapy. Results indicated episodic antiretroviral therapy was not useful in reducing morbidity or mortality with HIV/AIDS as compared to continuous therapy.

Although many methods for assessing adherence have been developed, most are not feasible for busy clinical settings. Using patients from the Adherence and Efficacy of Protease inhibitor Therapy (ADEPT) study (1998-2000), we systematically evaluated the relationship between psychosocial, environmental, clinical, and other factors with adherence to create composite variables (CVs) that are efficient with high sensitivity for detecting nonadherence and great potential for busy clinics. Eligible patients were protease inhibitor naive or started a regimen within 3 months from baseline. Of the 128 patients who responded to survey at baseline, weeks 8, 24, and/or 48, mean (standard deviation [SD]) age was 39.3 (8.2) years with 81% male. About half of the patients were Latino, followed by 28% African American and 14% Caucasian. Sixteen percent reported injection drug use, and 40% had male-male sex. Mean CD4 count was 184.8 cells/[mm.sup.3] with a range from 1 to 1130 cells/[mm.sup.3]. Thirty-two variables had a significant association with adherence at one or two time points and 9 were significantly associated with adherence over time. Among these significant factors, 8 also had a relationship with a clearly monotonic trend, by which 219 CVs were formed. Among these CVs, 8 were significantly associated with adherence and had a relationship with monotonic trend. Compared to traditional self-reported adherence, CVs had much higher sensitivities (p < 0.001) for detecting nonadherence. We conclude that CVs consisting of a combination of psychological, behavior, and adherence questions may be reasonable substitutes for direct adherence questions, which are limited by problems with recall and social biases. Trust in physicians, having a child, history of substance use, CD4 count, and belief that antiretrovirals can help living longer or improve quality of life can efficiently predict nonadherence. Because these variables are readily obtainable in clinical settings, these selected questions may provide a clinically useful means of screening patients for antiretroviral medication nonadherence.

A test was conducted to assess the efficacy and safety of emtricitabine as compared to stavudine in combination with didanosine and efavirenz. It was found that drug, emtricitabine administered once daily showed greater virological efficacy, steady response and tolerability as compared to stavudine administered twice daily combined with didanosine and efavirenz.

A double-blind study, involving three antiretroviral regimens for the initial treatment of patients infected with HIV-1:zidovudine-lamivudine-abacavir, zidovudine-lamivudine plus efavirenz, and zidovudine-lamivudine-abacavir plus efavirenz, is presented.

Acquired resistance to antiretroviral agents is an established sequela of HIV pharmacotherapy. Viral mutations can confer reduced susceptibility to antiretroviral medications, resulting in virologic and clinical failure in more than half of treated patients. Cross-resistance that can develop within each drug class leads to the progressive loss of future therapeutic options for individual patients. Although protease inhibitors (PIs) are a potent class of antiretrovirals, resistance can still develop rapidly, and multiple-PI resistance has become a serious, growing clinical problem. Development of rational treatment strategies that recognize specific patterns of cross-resistance among PIs are needed to help clinicians choose the most appropriate PI. Rational sequencing of PI use should be based on genotypic and phenotypic resistance testing. Maintaining higher drug plasma levels or using specific PI combinations may also diminish PI cross-resistance. New agents that are less likely to induce or be susceptible to cross-resistance will be of value in HIV treatment. This article reviews the acquisition of resistance to currently available PIs, discussing the drug-specific mutational patterns and evidence of clinical cross-resistance. The resistance profiles of two newer PIs, atazanavir and tipranavir, are also presented.

The objective of this pilot study was to examine attitudes toward protease inhibitors (PIs) among HIV-infected individuals and to assess the relationship between PI attitudes and adherence to PIs. Respondents were recruited from four AIDS service organizations in New York City; the total sample consisted of 97 HIV-infected individuals who were taking a PI. The sample consisted largely of African Americans and Latinos from inner city areas, and most had a low level of education. Adherence was suboptimal, with more than 50% of respondents failing to take their PI medications exactly as prescribed within the previous month. Individuals who had recently used illegal drugs within the past 6 months were more likely to be nonadherent to PIs. Those who were not adherent to PI medications reported greater concern about the side effects of PIs and were more likely to believe that it was acceptable to skip doses of PIs.

For several years, protease inhibitor (PI)-containing antiretroviral treatment (ART) regimens have demonstrated long-term virologic and immunologic benefits and good durability of response. However, first-generation PIs have been associated with high pill burdens, gastrointestinal side effects, perturbation of lipid levels and glucose metabolism, and, in some cases, food and hydration requirements. Coadministration of low-dose ritonavir with PIs has enhanced their pharmacokinetic profile (lower doses, fewer pills, less frequent dosing schedules) and pharmacodynamics (increased potency, especially against resistant viruses) but has also been associated with increases in lipid levels. Two new PIs, atazanavir and 908 (fosamprenavir), may offer salvageable PI treatment options and may also address issues of potency, tolerability, and convenience by requiring fewer pills and causing fewer lipid and glucose perturbations than current PI options. The availability of these novel PIs may improve long-term treatment options for many patients.

In order to establish the role of the protease inhibitor nelfinavir in current clinical practice, a prospective 18-month open-label comparison of efficacy and tolerability of nelfinavir was performed among HIV-infected patients who either incorporated nelfinavir in their first-line highly active antiretroviral therapy (HAART) regimen (group A, 57 patients), or who added nelfinavir to a rescue antiretroviral regimen (following at least two attempts with protease inhibitor-based HAART) (group B, 67 patients). All evaluable data were analyzed according to the prior and concurrent antiretroviral therapy, including genotypic resistance assays for patients undergoing salvage therapy. A significantly better virologic outcome (as expressed by a > 2 [log.sub.10] drop of plasma viremia versus baseline or attainment of undetectable levels), was shown among patients belonging to group A versus group B, where a number of genotypic mutations possibly elicited by previous anti-HIV treatment strongly impaired a potent and sustained nelfinavir activity. On the whole, the immunologic response (as expressed by the mean [CD4.sup.+] lymphocyte count versus baseline), substantially paralleled the virologic one in all analyzed subgroups, but a tendency toward a maintained immunologic competence was also observed in the majority of patients experiencing virologic failure. Nelfinavir introduction was sufficiently safe, because a limited percentage of patients suffered from mild-to moderate, novel, or continuing adverse events, which proved significantly more frequent in the salvage group but did not affect adherence to HAART.

A skin cream containing the antiviral drug penciclovir appears to be effective in treating cold sores in the mouth, according to a study of 4,573 people. Cold sores are caused by a virus called herpes simplex and the medical name for cold sores is herpes simplex labialis.

Aims: To assess the 'real life' effectiveness of different antiretroviral therapies (ART). Methods: A retrospective multicentre observational study in 150 HIV-1 vertically infected children on the progression to AIDS (study [...]