1,721,235 research outputs found
Tenofovir, another inexpensive, well-known and widely available old drug repurposed for sars-cov-2 infection
Full text linkSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is spreading worldwide with different clinical manifestations. Age and comorbidities may explain severity in critical cases and people living with human immunodeficiency virus (HIV) might be at particularly high risk for severe progression. Nonetheless, current data, although sometimes contradictory, do not confirm higher morbidity, risk of more severe COVID-19 or higher mortality in HIV-infected people with complete access to antiretroviral therapy (ART). A possible protective role of ART has been hypothesized to explain these observations. Anti-viral drugs used to treat HIV infection have been repurposed for COVID-19 treatment; this is also based on previous studies on severe acute respiratory syndrome virus (SARS-CoV) and Middle East respiratory syndrome virus (MERS-CoV). Among them, lopinavir/ritonavir, an inhibitor of viral protease, was extensively used early in the pandemic but it was soon abandoned due to lack of effectiveness in clinical trials. However, remdesivir, a nucleotide analog that acts as reverse-transcriptase inhibitor, which was tested early during the pandemic because of its wide range of antiviral activity against several RNA viruses and its safety profile, is currently the only antiviral medication approved for COVID-19. Tenofovir, another nucleotide analog used extensively for HIV treatment and pre-exposure prophylaxis (PrEP), has also been hypothesized as effective in COVID-19. No data on tenofovir’s efficacy in coronavirus infections other than COVID-19 are currently available, although information relating to SARS-CoV-2 infection is starting to come out. Here, we review the currently available evidence on tenofovir’s efficacy against SARS-CoV-2
The possible mechanisms of action of 4-aminoquinolines (chloroquine/hydroxychloroquine) against Sars-Cov-2 infection (COVID-19): A role for iron homeostasis?
Full text linkThe anti-malarial drugs chloroquine (CQ) and primarily the less toxic hydroxychloroquine (HCQ) are currently used to treat autoimmune diseases for their immunomodulatory and anti-thrombotic properties. They have also been proposed for the treatment of several viral infections, due to their anti-viral effects in cell cultures and animal models, and, currently, for the treatment of coronavirus disease 2019 (COVID-19), the pandemic severe acute respiratory syndrome caused by coronavirus 2 (Sars-Cov-2) infection that is spreading all over the world. Although in some recent studies a clinical improvement in COVID-19 patients has been observed, the clinical efficacy of CQ and HCQ in COVID-19 has yet to be proven with randomized controlled studies, many of which are currently ongoing, also considering pharmacokinetics, optimal dosing regimen, therapeutic level and duration of treatment and taking into account patients with different severity degrees of disease. Here we review what is currently known on the mechanisms of action of CQ and HCQ as anti-viral, anti-inflammatory and anti-thrombotic drugs and discuss the up-to-date experimental evidence on the potential mechanisms of action of CQ/HCQ in Sars-Cov2 infection and the current clinical knowledge on their efficacy in the treatment of COVID-19 patients. Given the role of iron in several human viral infections, we also propose a different insight into a number of CQ and HCQ pharmacological effects, suggesting a potential involvement of iron homeostasis in Sars-Cov-2 infection and COVID-19 clinical course
Dolutegravir-rilpivirine: first 2-drug regimen for HIV-positive adults
No full textIntroduction: New strategies for HIV treatment are being investigated to reduce drug-exposure, toxicities, and costs. Dolutegravir (DTG) 50 mg/rilpivirine (RPV) 25 mg was approved in November 2017 by FDA and in May 2018 by the European Medicines Agency (EMA). It is indicated as a complete regimen for HIV-1 infected adults with undetectable plasmatic HIV-RNA for at least 6 months 10 on their current HIV treatment combination. Its approval was based on the data of two randomized, multicenter, non-inferiority trials (SWORD-1 and SWORD-2). Areas covered: We reviewed data from literature about DTG and RPV. We mainly focused on the efficacy and on the safety of this new dual therapy. Its impact on renal function, its bone and cardiovascular profile, its reservoir penetration and its role on nflammation were also evaluated. Expert commentary: Dual therapies may be an attractive alternative to standard triple regimens in terms of tolerability and simplicity. Long-term efficacy of DTG and RPV dual regimen need to be confirmed, where only the extensive use of this new treatment and a longer follow-up will give us the answer
Correction to: Zanella et al. tenofovir, another inexpensive, well known and widely available old drug repurposed for sars-cov-2 infection. pharmaceuticals 2021, 14, 454
No full textText Correction There was an error in the original article [1]. In the Abstract, page 1, line 12 from the top, the sentence “ . . . remdesivir, a nucleotide analog that acts as reverse-transcriptase inhibitor, . . . ” is incorrect. A correction has been made to the Abstract. The incorrect sentence must be replaced with “ . . . remdesivir, a nucleotide analog that acts as RNA-dependent RNA-polymerase inhibitor, . . . ”. The authors apologize for any inconvenience caused and state that the scientific conclusions are unaffected. The original article has been updated.
Knowledge and Attitudes towards HIV and HCV among the Population Attending the Fast-Track Cities Mobile Unit in Brescia, Italy
No full textThe Infectious and Tropical Diseases Department of the University of Brescia organized free rapid screening tests for HIV and HCV as part of the Fast-Track City commitment. A cross-sectional study was conducted, consisting of an anonymous multiple-choice questionnaire that was administered to individuals who underwent the screening or consultation. The study aimed to compare knowledge and attitudes towards HIV and HCV between age groups (18–40 vs. >40) and sexual orientations (heterosexual vs. LGBTQ+). Overall, 333 questionnaires were completed. Overall, only 107 (32%) of respondents knew how HIV is transmitted. Major differences were shown between different age groups, where people under the age of 40 had a significantly higher correct response rate than people over 40 (n = 101; 39% versus n = 6; 7.8%, p < 0.00001). Similarly, almost half of LGBTQI+ people (n = 28; 44.4%) gave the correct answer, versus 30% (n = 79) of heterosexuals (p = 0.0359). Only 9.6% of the population demonstrated high levels of knowledge for both HIV and HCV. Our study highlights that misconceptions about HIV and HCV should be addressed in prevention and education programs, whose target should also be specific populations
Monoclonal antibodies against sars-cov-2: Current scenario and future perspectives
Full text linkMonoclonal antibodies (mAbs) have been known since the 1970s. However, their therapeutic potential in the medical field has recently emerged, with the advancement of manufacturing techniques. Initially exploited mainly in the oncology field, mAbs have become increasingly relevant in Infectious Diseases. Numerous mAbs have been developed against SARS-CoV 2 and have proven their effectiveness, especially in the management of the mild-to-moderate disease. In this review, we describe the monoclonal antibodies currently authorized for the treatment of the coronavirus disease 19 (COVID-19) and offer an insight into the clinical trials that led to their approval. We discuss the mechanisms of action and methods of administration as well as the prophylactic and therapeutic labelled indications (both in outpatient and hospital settings). Furthermore, we address the critical issues regarding mAbs, focusing on their effectiveness against the variants of concern (VoC) and their role now that a large part of the population has been vaccinated. The purpose is to offer the clinician an up-to-date overview of a therapeutic tool that could prove decisive in treating patients at high risk of progression to severe disease
An HIV elite controller patient carrying the homozygous H63D variant in the homeostatic iron regulator gene: A case report
Full text linkRATIONALE: HIV elite controllers represent a rare subset of persons living with HIV, able to spontaneously control viral replication without antiviral therapy. HLA-B∗57 and HLA-B∗27 alleles are associated to efficient polyfunctional CD8+ T-cell response and are overrepresented in elite controllers but these alleles alone incompletely explain spontaneous HIV replication control in these subjects. Further mechanisms involved in innate and adaptive immune response and host genetics may contribute to this control. In this context, the homeostatic iron regulator (HFE) gene encodes a major histocompatibility complex-class-I-like molecule involved in both innate immunity, acting also through autophagy regulation, and iron homeostasis, strictly related to immune functions and susceptibility to infections. PATIENT CONCERNS: Homozygousity for the p.His63Asp (H63D) variant in the HFE gene was identified in an 80-year-old HIV-infected woman with spontaneous control of viral replication. DIAGNOSIS: HIV-1 RNA was undetectable in patient's serum with a routine assay and an ultra-sensitive assay (65 years and screened for polymorphisms in genes belonging to several pathways involved in neuroinflammation. OUTCOMES: The woman had CD4+ and CD8+ T cell normal values and spontaneously controlled serum HIV-1 RNA levels for 30 years. LESSONS: We assume that the interplay between the HFE H63D variant in homozygosity and innate immunity, perhaps through autophagy regulation, could play a role in HIV-1 replication control in our patient. This hypothesis needs to be explored in in vitro and in vivo studies. Understanding mechanisms involved in spontaneous control of HIV-1 replication remains indeed a challenge due to its possible implications for HIV cure research
Osteoporosis in HIV patients: an emerging clinical issue
No full textViene descritta la importanza del metabolismo osseo in corso di infezione da HIV, con particolare riferimento al problema ed alla prevalemza di lezioni osteoporotiche in tale popolazion
Lymphocyte homeostasis is maintained in perinatally HIV-infected patients after three decades of life
No full textBACKGROUND: While immunosenescence, defined as reduced production of new lymphocytes, restriction of T-cell receptor repertoire and telomeres shortening, has been extensively evaluated in HIV-infected children and adults, no data about these parameters are available in perinatally-infected patients with very long-lasting HIV infection.
METHODS: We compared thymic and bone marrow output, telomere length (measured by Real-Time PCR) and T-cell receptor repertoire (determined by spectratyping) of 21 perinatally HIV-infected subjects (with a median of 27 years of infection) with those of 19 age-matched non-perinatally HIV-infected patients and 40 healthy controls. All patients received a combined antiretroviral therapy.
RESULTS: While thymic and bone marrow output were not different among the analyzed groups, telomere length in peripheral blood cells and T-cell receptor diversity were significantly lower in HIV-perinatally and non-perinatally infected individuals compared to healthy controls.
CONCLUSIONS: In HIV-infected subjects, a normal thymic output together with a reduced telomere length and a restricted T-cell receptor repertoire could be explained by the shift of newly produced cells into memory subsets. This phenomenon may allow to control viral infection and maintain peripheral homeostasis
Low prevalence of symptomatic thyroid diseases and thyroid cancers in HIV-infected patients
No full textThyroid diseases (TDs) have been widely associated with HIV infection. However, data about TDs prevalence and distribution are controversial, and few published studies are available. The aim of our study was to assess prevalence and risk factors of symptomatic thyroid disturbances, including thyroid cancers, in a large cohort of HIV-infected patients. A retrospective cohort study was performed at the Department of Infectious and Tropical Diseases of the University of Brescia, Italy, in the period 2005–2017. We identified all HIV-positive patients with a diagnosis of symptomatic TD in the electronic database of our Department (HIVeDB); we also operated a record-linkage between our data and the Health Protection Agency database (HPADB) of Brescia Province. Multivariate logistic regression analysis was used to determine risk factors associated with TDs onset; an incidence rate analysis was also performed. During the study period, 6343 HIV-infected patients have been followed at our Department; 123 received a diagnosis of symptomatic TD (1.94% of the entire cohort). In the TDs group, almost half of patients were females (n = 59, 48%), mean age was 47.15 years (SD: 11.56). At TD diagnosis, mean T CD4+ cell count was 491 cell/uL and most patients showed undetectable HIV-RNA (n = 117, 95.12%). Among them, 81 patients were found to have hypothyroidism (63 with Hashimoto’s thyroiditis), 21 hyperthyroidism (17 suffered from Graves’ disease), while 11 subjects were diagnosed with a primitive thyroid cancer. Papillary thyroid cancer was the most frequent histotype (n = 7, 63.63%), followed by medullary (n = 2, 18.18%) and follicular thyroid cancer (n = 1, 9.1%). Male gender was a protective factor for TDs development, especially for hypothyroidism (p < 0.001); age emerged as a variable associated with both hypothyroidism (p = 0.03) and thyroid cancer (p = 0.03), while CD4+ cell nadir <200 cell/mm3 was associated with symptomatic hyperthyroidism (p = 0.005). To conclude, symptomatic thyroid dysfunctions rate in well-treated HIV-infected patients is low. Age and gender are crucial elements in the onset of thyroid abnormalities, together with T CD4+ cell nadir. Interestingly, medullary thyroid cancer seems to be much more frequent in HIV-infected patients compared to the general population
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