Editorial

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Open AccessEditorial

Special Issue “Efficacy and Safety of Antiviral Therapy”

by Agnese Colpani, Andrea De Vito and Giordano Madeddu

Viruses 2023, 15(7), 1411; https://doi.org/10.3390/v15071411 - 21 Jun 2023

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This comprehensive collection of papers contains a wide range of studies and observations centered on antiviral therapies, with a particular focus on HIV and other viral infections such as monkeypox and SARS-CoV-2 [...] Full article

(This article belongs to the Special Issue Efficacy and Safety of Antiviral Therapy)

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15 pages, 2398 KiB

Open AccessArticle

Immune Reconstitution and Safe Metabolic Profile after the Switch to Bictegravir/Emtricitabine/Tenofovir Alafenamide Fumarate among Virologically Controlled PLWH: A 96 Week Update from the BICTEL Cohort

by Alessandro Lazzaro, Diana Bianchini, Elio Gentilini Cacciola, Ivano Mezzaroma, Mario Falciano, Carolina Andreoni, Caterina Fimiani, Letizia Santinelli, Luca Maddaloni, Ginevra Bugani, Giancarlo Ceccarelli, Claudio Maria Mastroianni and Gabriella d’Ettorre

Viruses 2023, 15(6), 1222; https://doi.org/10.3390/v15061222 - 23 May 2023

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Abstract

Background: Bictegravir/emtricitabine/tenofovir alafenamide fumarate (BIC/FTC/TAF) is a recommended once-daily single-tablet regimen for the treatment of people living with HIV (PLWH). We aimed to assess efficacy, safety, and tolerability of BIC/FTC/TAF among PLWH, with a specific focus on people older than 55 years. Methods: [...] Read more.

Background: Bictegravir/emtricitabine/tenofovir alafenamide fumarate (BIC/FTC/TAF) is a recommended once-daily single-tablet regimen for the treatment of people living with HIV (PLWH). We aimed to assess efficacy, safety, and tolerability of BIC/FTC/TAF among PLWH, with a specific focus on people older than 55 years. Methods: We recruited an observational retrospective real-life cohort, including all PLWH who underwent a therapeutic switch to BIC/FTC/TAF, independently from the previous treatment regimen (the BICTEL cohort). Longitudinal nonparametric analyses and linear models were built. Results: After 96 weeks of follow-up, 164 PLWH were included, with 106 older than 55. Both the intention-to-treat and the per-protocol analysis showed low rates of virologic failure, independent of the pre-switch anchor drug. At week 96, a significant increase in CD4⁺ T cell count and in CD4⁺/CD8⁺ ratio was observed, inversely correlated with baseline immune status. Fasting serum lipid profile, total body weight, BMI, and hepatic function were not affected by the switch, without new onset of metabolic syndrome or weight gain. Compared to baseline, we observed a renal function worsening which is worthy of further follow-up. Conclusion: BIC/FTC/TAF is an effective, safe, and well-tolerated switching strategy for PLWH, especially among those older than 55. Full article

(This article belongs to the Special Issue Efficacy and Safety of Antiviral Therapy)

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12 pages, 939 KiB

Open AccessArticle

Tenofovir-Containing Antiretroviral Therapy and Clinical Outcomes of SARS-CoV-2 Infection in People Living with HIV

by María F. Rombini, Diego Cecchini, Sofía Diana Menendez, Liliana Calanni, Rosana Cuini, Elena Obieta, María M. Greco, Fabricio Morales, Laura Morganti, Claudia Migazzi, Yasmin El Kozah, Pablo Parenti, Isabel Cassetti and on behalf of the COVIDARE Study Team

Viruses 2023, 15(5), 1127; https://doi.org/10.3390/v15051127 - 09 May 2023

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Abstract

Tenofovir has been hypothesized to be effective against COVID-19 and is available as two prodrugs, tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF), both part of antiretroviral therapy (ART) regimens. People living with human immunodeficiency virus (PLWH) might be at higher risk for [...] Read more.

Tenofovir has been hypothesized to be effective against COVID-19 and is available as two prodrugs, tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF), both part of antiretroviral therapy (ART) regimens. People living with human immunodeficiency virus (PLWH) might be at higher risk for COVID-19 progression; however, information about the impact of tenofovir on COVID-19 clinical outcomes remains controversial. The COVIDARE is a prospective observational multicentric study in Argentina. PLWH with COVID-19 were enrolled from September 2020 to mid-June 2022. Patients were stratified according to baseline ART into those with tenofovir (TDF or TAF) and those without. Univariate and multivariate analyses were performed to evaluate the impact of tenofovir vs. non-tenofovir-containing regimens on major clinical outcomes. Of the 1155 subjects evaluated, 927 (80%) received tenofovir-based ART (79% TDF, 21% TAF) whilst the remaining population was under non-tenofovir regimens. The non-tenofovir group had older age and a higher prevalence of heart and kidney disease. Regarding the prevalence of symptomatic COVID-19, tomographic findings, hospitalization, and mortality, no differences were observed. The oxygen therapy requirement was higher in the non-tenofovir group. In the multivariate analyses, a first model with adjustment for viral load, CD4 T-cell count, and overall comorbidities showed that oxygen requirement was associated with non-tenofovir ART. In a second model with adjustment by chronic kidney disease, tenofovir exposure was not statistically significant. Full article

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13 pages, 1016 KiB

Open AccessArticle

Efficacy and Durability of Dolutegravir- or Darunavir-Based Regimens in ART-Naïve AIDS- or Late-Presenting HIV-Infected Patients

by Massimiliano Fabbiani, Melissa Masini, Barbara Rossetti, Arturo Ciccullo, Vanni Borghi, Filippo Lagi, Amedeo Capetti, Manuela Colafigli, Francesca Panza, Gianmaria Baldin, Cristina Mussini, Gaetana Sterrantino, Damiano Farinacci, Francesca Montagnani, Mario Tumbarello and Simona Di Giambenedetto

Viruses 2023, 15(5), 1123; https://doi.org/10.3390/v15051123 - 08 May 2023

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Abstract

Background: Since limited data are available, we aimed to compare the efficacy and durability of dolutegravir and darunavir in advanced naïve patients. Methods: Retrospective multicenter study including AIDS- or late-presenting (def. CD4 ≤ 200/µL) HIV-infected patients starting dolutegravir or ritonavir/cobicistat-boosted darunavir+2NRTIs. Patients were [...] Read more.

Background: Since limited data are available, we aimed to compare the efficacy and durability of dolutegravir and darunavir in advanced naïve patients. Methods: Retrospective multicenter study including AIDS- or late-presenting (def. CD4 ≤ 200/µL) HIV-infected patients starting dolutegravir or ritonavir/cobicistat-boosted darunavir+2NRTIs. Patients were followed from the date of first-line therapy initiation (baseline, BL) to the discontinuation of darunavir or dolutegravir, or for a maximum of 36 months of follow-up. Results: Overall 308 patients (79.2% males, median age 43 years, 40.3% AIDS-presenters, median CD4 66 cells/µL) were enrolled; 181 (58.8%) and 127 (41.2%) were treated with dolutegravir and darunavir, respectively. Incidence of treatment discontinuation (TD), virological failure (VF, defined as a single HIV-RNA > 1000 cp/mL or two consecutive HIV-RNA > 50 cp/mL after 6 months of therapy or after virological suppression had been achieved), treatment failure (the first of TD or VF), and optimal immunological recovery (defined as CD4 ≥ 500/µL + CD4 ≥ 30% + CD4/CD8 ≥ 1) were 21.9, 5.2, 25.6 and 1.4 per 100 person-years of follow-up, respectively, without significant differences between dolutegravir and darunavir (p > 0.05 for all outcomes). However, a higher estimated probability of TD for central nervous system (CNS) toxicity (at 36 months: 11.7% vs. 0%, p = 0.002) was observed for dolutegravir, whereas darunavir showed a higher probability of TD for simplification (at 36 months: 21.3% vs. 5.7%, p = 0.046). Conclusions: Dolutegravir and darunavir showed similar efficacy in AIDS- and late-presenting patients. A higher risk of TD due to CNS toxicity was observed with dolutegravir, and a higher probability of treatment simplification with darunavir. Full article

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6 pages, 220 KiB

Open AccessCommunication

Changes in Metabolic Profile in PLWHIV Switching to Doravirine-Based Regimen

by Valentina Iannone, Rosa Anna Passerotto, Francesco Lamanna, Rebecca Jo Steiner, Francesca Lombardi, Pierluigi Francesco Salvo, Alex Dusina, Damiano Farinacci, Alberto Borghetti, Simona Di Giambenedetto and Arturo Ciccullo

Viruses 2023, 15(5), 1046; https://doi.org/10.3390/v15051046 - 25 Apr 2023

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Abstract

Thanks to the modern ARV regimens and the fact that the morbidity and mortality of metabolic syndrome increases with age, clinicians are continuously researching effective and safe antiretroviral regimens with low impact on the lipid profile. Doravirine (DOR) is the latest non-nucleoside reverse-transcriptase [...] Read more.

Thanks to the modern ARV regimens and the fact that the morbidity and mortality of metabolic syndrome increases with age, clinicians are continuously researching effective and safe antiretroviral regimens with low impact on the lipid profile. Doravirine (DOR) is the latest non-nucleoside reverse-transcriptase inhibitor (NNRTI) that shows long-term safety and tolerability and a favorable lipid profile. The aim of this study is to assess the impact of DOR-based three-drug regimens on the lipid profile in clinical practice. We retrospectively analyzed a cohort of 38 treatment-experienced, virologically suppressed people living with HIV (PLWH) switching to this regimen, following the eligibility criteria. We carried out comparison analysis of immunological and metabolic parameters between baseline and 48 weeks of follow up. In our cohort of treatment-experienced, virologically suppressed PLWH, three-drug regimens with DOR showed good efficacy and a positive profile on lipid metabolism at 48 weeks of follow up. Full article

(This article belongs to the Special Issue Efficacy and Safety of Antiviral Therapy)

15 pages, 2374 KiB

Open AccessArticle

Effectiveness, Tolerability and Prescribing Choice of Antiviral Molecules Molnupiravir, Remdesivir and Nirmatrelvir/r: A Real-World Comparison in the First Ten Months of Use

by Cosmo Del Borgo, Silvia Garattini, Carolina Bortignon, Anna Carraro, Daniela Di Trento, Andrea Gasperin, Alessandra Grimaldi, Sara Giovanna De Maria, Sara Corazza, Tiziana Tieghi, Valeria Belvisi, Blerta Kertusha, Margherita De Masi, Ombretta D’Onofrio, Gabriele Bagaglini, Gabriella Bonanni, Paola Zuccalà, Paolo Fabietti, Eeva Tortellini, Mariasilvia Guardiani, Alessandra Spagnoli, Raffaella Marocco, Danilo Alunni Fegatelli, Miriam Lichtner and LATINA COVID-group Show full author list Hide full author list

Viruses 2023, 15(4), 1025; https://doi.org/10.3390/v15041025 - 21 Apr 2023

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Abstract

In 2022, three antiviral drugs—molnupiravir, remdesivir and nirmatrelvir/ritonavir—were introduced for treatment of mild-to-moderate COVID-19 in high-risk patients. The aim of this study is the evaluation of their effectiveness and tolerability in a real-life setting. A single-center observational study was set up, with the [...] Read more.

In 2022, three antiviral drugs—molnupiravir, remdesivir and nirmatrelvir/ritonavir—were introduced for treatment of mild-to-moderate COVID-19 in high-risk patients. The aim of this study is the evaluation of their effectiveness and tolerability in a real-life setting. A single-center observational study was set up, with the involvement of 1118 patients, with complete follow-up data, treated between the 5th of January and the 3rd of October 2022 at Santa Maria Goretti’s hospital in Latina, Central Italy. A univariable and a multivariable analysis were performed on clinical and demographic data and composite outcome, the persistence of symptoms at 30 days and time to negativization, respectively. The three antivirals showed a similar effectiveness in containing the progression of the infection to severe COVID-19 and a good tolerability in the absence of serious adverse effects. Persistence of symptoms after 30 days was more common in females than males and less common in patients treated with molnupiravir and nirmatrelvir/r. The availability of different antiviral molecules is a strong tool and, if correctly prescribed, they can have a significant role in changing the natural history of infection for frail persons, in which vaccination could be not sufficient for the prevention of severe COVID-19. Full article

(This article belongs to the Special Issue Efficacy and Safety of Antiviral Therapy)

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14 pages, 3558 KiB

Open AccessArticle

Topical Protease Inhibitor Decreases Anal Carcinogenesis in a Transgenic Mouse Model of HPV Anal Disease

by Laura C. Gunder, Hillary R. Johnson, Evan Yao, Tyra H. Moyer, Heather A. Green, Nathan Sherer, Wei Zhang and Evie H. Carchman

Viruses 2023, 15(4), 1013; https://doi.org/10.3390/v15041013 - 20 Apr 2023

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Abstract

Anal cancer is a major health problem. This study seeks to determine if the topical protease inhibitor Saquinavir (SQV), is effective at the prevention of anal cancer in transgenic mice with established anal dysplasia. K14E6/E7 mice were entered into the study when the [...] Read more.

Anal cancer is a major health problem. This study seeks to determine if the topical protease inhibitor Saquinavir (SQV), is effective at the prevention of anal cancer in transgenic mice with established anal dysplasia. K14E6/E7 mice were entered into the study when the majority spontaneously developed high-grade anal dysplasia. To ensure carcinoma development, a subset of the mice was treated with a topical carcinogen: 7,12-Dimethylbenz[a]anthracene (DMBA). Treatment groups included: no treatment, DMBA only, and topical SQV with/without DMBA. After 20 weeks of treatment, anal tissue was harvested and evaluated histologically. SQV was quantified in the blood and anal tissue, and tissue samples underwent analysis for E6, E7, p53, and pRb. There was minimal systemic absorption of SQV in the sera despite high tissue concentrations. There were no differences in tumor-free survival between SQV-treated and respective control groups but there was a lower grade of histological disease in the mice treated with SQV compared to those untreated. Changes in E6 and E7 levels with SQV treatment suggest that SQV may function independently of E6 and E7. Topical SQV decreased histological disease progression in HPV transgenic mice with or without DMBA treatment without local side effects or significant systemic absorption. Full article

(This article belongs to the Special Issue Efficacy and Safety of Antiviral Therapy)

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12 pages, 1118 KiB

Open AccessArticle

Use of Remdesivir in Patients with SARS-CoV-2 Pneumonia in a Real-Life Setting during the Second and Third COVID-19 Epidemic Waves

by Raffaella Marocco, Cosmo Del Borgo, Eeva Tortellini, Silvia Garattini, Anna Carraro, Daniela Di Trento, Andrea Gasperin, Alessandra Grimaldi, Tiziana Tieghi, Valeria Belvisi, Blerta Kertusha, Mariasilvia Guardiani, Paola Zuccalà, Danilo Alunni Fegatelli, Alessandra Spagnoli, Miriam Lichtner and LATINA COVID-group

Viruses 2023, 15(4), 947; https://doi.org/10.3390/v15040947 - 11 Apr 2023

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Abstract

In this retrospective comparative study, we evaluated the effectiveness of remdesivir (RDSV) in patients with SARS-CoV-2 pneumonia. Individuals hospitalized between March 2020 and August 2022 at S.M. Goretti Hospital, Latina, with a positive test for SARS-CoV-2 and, concomitantly, pneumonia, were included. The overall [...] Read more.

In this retrospective comparative study, we evaluated the effectiveness of remdesivir (RDSV) in patients with SARS-CoV-2 pneumonia. Individuals hospitalized between March 2020 and August 2022 at S.M. Goretti Hospital, Latina, with a positive test for SARS-CoV-2 and, concomitantly, pneumonia, were included. The overall survival was the primary endpoint. The composite secondary endpoint included death or progression in severe ARDS at 40 days. The study population was stratified according to treatment into two groups: the RDSV group (patients treated with RDSV-based regimens) and the no-RDSV group (patients treated with any other, not RDSV-based, regimens). Factors associated with death and progression to severe ARDS or death were assessed by multivariable analysis. A total of 1153 patients (632 belonging to the RDSV group and 521 to the no-RDSV group) were studied. The groups were comparable in terms of sex, PaO2/FiO2 at admission, and duration of symptoms before hospitalization. Further, 54 patients (8.5%) in the RDSV group and 113 (21.7%) in the no-RDSV group (p < 0.001) died. RDSV was associated with a significantly reduced hazard ratio (HR) of death (HR, 0.69 [95% CI, 0.49–0.97]; p = 0.03), compared to the no-RDSV group, as well as a significantly reduced OR of progression in severe ARDS or death (OR, 0.70 [95% CI 0.49–0.98]; p = 0.04). An overall significantly higher survival rate was observed in the RDSV group (p < 0.001, by log-rank test). These findings reinforce the survival benefit of RDSV and support its routine clinical use for the treatment of COVID-19 patients. Full article

(This article belongs to the Special Issue Efficacy and Safety of Antiviral Therapy)

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15 pages, 620 KiB

Open AccessArticle

Causes of HIV Treatment Interruption during the Last 20 Years: A Multi-Cohort Real-Life Study

by Andrea De Vito, Elena Ricci, Barbara Menzaghi, Giancarlo Orofino, Canio Vito Martinelli, Nicola Squillace, Lucia Taramasso, Giuseppe Vittorio De Socio, Chiara Molteni, Laura Valsecchi, Cecilia Costa, Benedetto Maurizio Celesia, Giustino Parruti, Giovanni Francesco Pellicanò, Eleonora Sarchi, Antonio Cascio, Giovanni Cenderello, Katia Falasca, Antonio Di Biagio, Paolo Bonfanti and Giordano Madeddu Show full author list Hide full author list

Viruses 2023, 15(3), 720; https://doi.org/10.3390/v15030720 - 10 Mar 2023

Cited by 6 | Viewed by 1882

Abstract

In the last years, many antiretroviral drugs (ART) have been developed with increased efficacy. Nowadays, the main reasons for treatment switches are adverse events, proactive strategy or simplification. We conducted a retrospective cohort study to investigate the reason for treatment interruption in the [...] Read more.

In the last years, many antiretroviral drugs (ART) have been developed with increased efficacy. Nowadays, the main reasons for treatment switches are adverse events, proactive strategy or simplification. We conducted a retrospective cohort study to investigate the reason for treatment interruption in the last 20 years. We merged data of eight cohorts of the SCOLTA project: lopinavir/r (LPV), atazanavir/r (ATV), darunavir/r or /c (DRV), rilpivirine (RPV), raltegravir (RAL), elvitegravir/c (EVG), dolutegravir (DTG) and bictegravir (BIC). We included 4405 people with HIV (PWH). Overall, 664 (15.1%), 489 (11.1%), and 271 (6.2%) PWH interrupted the treatment in the first, second, and third years after starting a new ART. Looking at the interruption in the first year, the most frequent causes were adverse events (3.8%), loss to follow-up (3.7%), patients’ decisions (2.6%), treatment failure (1.7%), and simplification (1.3%). In the multivariate analysis regarding experienced patients, treatment with LPV, ATV, RPV or EVG/c, having less than 250 CD4 cells/mL, history of intravenous drug use, and HCV positivity were associated with an increased risk of interruption. In naive people, only LPV/r was associated with an increased risk of interruption, while RPV was associated with a lower risk. In conclusion, our data on more than 4400 PWH show that adverse events have represented the most frequent cause of treatment interruptions in the first year of ART (3.84%). Treatment discontinuations were more frequent during the first year of follow-up and decreased thereafter. First-generation PI in both naïve and experienced PWH, and EVG/c, in experienced PWH, were associated with a higher risk of treatment interruptions. Full article

(This article belongs to the Special Issue Efficacy and Safety of Antiviral Therapy)

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14 pages, 1533 KiB

Open AccessArticle

Human Monkeypox Experience in a Tertiary Level Hospital in Milan, Italy, between May and October 2022: Epidemiological Features and Clinical Characteristics

by Caterina Candela, Angelo Roberto Raccagni, Elena Bruzzesi, Costanza Bertoni, Alberto Rizzo, Gloria Gagliardi, Diana Canetti, Nicola Gianotti, Davide Mileto, Maria Rita Gismondo, Antonella Castagna and Silvia Nozza

Viruses 2023, 15(3), 667; https://doi.org/10.3390/v15030667 - 02 Mar 2023

Cited by 14 | Viewed by 2033

Abstract

Background: Monkeypox virus (mpxv) started to spread to Europe and North America at the beginning of the current outbreak in May 2022, and the World Health Organization (WHO) declared Human Monkeypox (mpox) as a public health emergency of international concern (PHEIC) in July [...] Read more.

Background: Monkeypox virus (mpxv) started to spread to Europe and North America at the beginning of the current outbreak in May 2022, and the World Health Organization (WHO) declared Human Monkeypox (mpox) as a public health emergency of international concern (PHEIC) in July 2022. The aim of this observational analysis is to describe demographical data, symptoms presentation and clinical course till outcome of individuals diagnosed with mpox, between May and October 2022, at our open-access Sexual Health Clinic in IRCCS San Raffaele Hospital in Milan, Italy. Methods: Among people who accessed our Sexual Health Clinic, we considered, as suspected diagnosis of mpox, individuals with consistent symptoms and epidemiological criteria. Following the physical examination, oropharyngeal, anal, genital and cutaneous swabs, plus plasma, urine and seminal fluid were collected as biological materials to detect mpxv DNA. We also performed a screening for sexually transmitted infections (STIs). Results: Overall, 140 individuals with mpox were included in this study. Median age was 37 (interquartile, IQR 33, 43) years old. Males were 137 (98%) and men who have sex with men (MSM) were 134 (96%). As risk factors, we detected travels abroad in 35 (25%) individuals and close contact with mpox cases in 49 (35%). There were 66 (47%) people living with HIV (PLWH). Most frequent symptoms were fever (59%), lymphadenopathy (57%), cutaneous (77%), genital (42%), anal (34%) and oral (26%) lesions, proctitis (39%), sore throat (22%) and generalized rash (5%). At mpox diagnosis, we also observed N. gonorrhoeae in 18 (13%) cases, syphilis in 14 (10%) and C. trachomatis in 12 (9%). Two (1%) people received a concomitant diagnosis of HIV infection. We attended to 21 (15%) complications, with nine (6%) cases of hospitalization including six (IQR 3,7) median hospital days. Forty-five (32%) patients were treated with non-steroidal anti-inflammatory drugs (NSAIDs), 37 (26%) with antibiotics and eight (6%) with antiviral drugs. Conclusions: Similarly to other international cohorts, sexual transmission was most frequently present, and concomitant STIs were common. Symptoms were heterogenous, self-resolving and responsive to therapy. Hospitalization was necessary in few patients. There is uncertainty about the future development of mpox and further studies (e.g., potential disease reservoirs, other possible means of transmission, predictors of severe disease) are still needed. Full article

(This article belongs to the Special Issue Efficacy and Safety of Antiviral Therapy)

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13 pages, 1025 KiB

Open AccessArticle

Do All Critically Ill Patients with COVID-19 Disease Benefit from Adding Tocilizumab to Glucocorticoids? A Retrospective Cohort Study

by Cristina Mussini, Alessandro Cozzi-Lepri, Marianna Meschiari, Erica Franceschini, Giulia Burastero, Matteo Faltoni, Giacomo Franceschi, Vittorio Iadisernia, Sara Volpi, Andrea Dessilani, Licia Gozzi, Jacopo Conti, Martina Del Monte, Jovana Milic, Vanni Borghi, Roberto Tonelli, Lucio Brugioni, Elisa Romagnoli, Antonello Pietrangelo, Elena Corradini, Massimo Girardis, Stefano Busani, Andrea Cossarizza, Enrico Clini and Giovanni Guaraldi Show full author list Hide full author list

Viruses 2023, 15(2), 294; https://doi.org/10.3390/v15020294 - 20 Jan 2023

Cited by 2 | Viewed by 1727

Abstract

Background: Treatment guidelines recommend the tocilizumab use in patients with a CRP of >7.5 mg/dL. We aimed to estimate the causal effect of glucocorticoids + tocilizumab on mortality overall and after stratification for PaO₂/FiO₂ ratio and CRP levels. Methods: This [...] Read more.

Background: Treatment guidelines recommend the tocilizumab use in patients with a CRP of >7.5 mg/dL. We aimed to estimate the causal effect of glucocorticoids + tocilizumab on mortality overall and after stratification for PaO₂/FiO₂ ratio and CRP levels. Methods: This was an observational cohort study of patients with severe COVID-19 pneumonia. The primary endpoint was day 28 mortality. Survival analysis was conducted to estimate the conditional and average causal effect of glucocorticoids + tocilizumab vs. glucocorticoids alone using Kaplan–Meier curves and Cox regression models with a time-varying variable for the intervention. The hypothesis of the existence of effect measure modification by CRP and PaO₂/FiO₂ ratio was tested by including an interaction term in the model. Results: In total, 992 patients, median age 69 years, 72.9% males, 597 (60.2%) treated with monotherapy, and 395 (31.8%), adding tocilizumab upon respiratory deterioration, were included. At BL, the two groups differed for median values of CRP (6 vs. 7 mg/dL; p < 0.001) and PaO₂/FiO₂ ratio (276 vs. 235 mmHg; p < 0.001). In the unadjusted analysis, the mortality was similar in the two groups, but after adjustment for key confounders, a significant effect of glucocorticoids + tocilizumab was observed (adjusted hazard ratio (aHR) = 0.59, 95% CI: 0.38–0.90). Although the study was not powered to detect interactions (p = 0.41), there was a signal for glucocorticoids + tocilizumab to have a larger effect in subsets, especially participants with high levels of CRP at intensification. Conclusions: Our data confirm that glucocorticoids + tocilizumab vs. glucocorticoids alone confers a survival benefit only in patients with a CRP > 7.5 mg/dL prior to treatment initiation and the largest effect for a CRP > 15 mg/dL. Large randomized studies are needed to establish an exact cut-off for clinical use. Full article

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11 pages, 480 KiB

Open AccessArticle

Impact of Early SARS-CoV-2 Antiviral Therapy on Disease Progression

by Andrea De Vito, Agnese Colpani, Laura Saderi, Mariangela Puci, Beatrice Zauli, Vito Fiore, Marco Fois, Maria Chiara Meloni, Alessandra Bitti, Cosimo Di Castri, Ivana Maida, Sergio Babudieri, Giovanni Sotgiu and Giordano Madeddu

Viruses 2023, 15(1), 71; https://doi.org/10.3390/v15010071 - 27 Dec 2022

Cited by 18 | Viewed by 2436

Abstract

Since the start of the SARS-CoV-2 pandemic, several treatments have been proposed to prevent the progression of the disease. Currently, three antiviral (molnupiravir, nirmaltrevir/r, remdesivir) and two monoclonal antibodies (casirivimab/imdevimab and sotrovimab) are available in Italy. Therefore, we aimed to evaluate the presence [...] Read more.

Since the start of the SARS-CoV-2 pandemic, several treatments have been proposed to prevent the progression of the disease. Currently, three antiviral (molnupiravir, nirmaltrevir/r, remdesivir) and two monoclonal antibodies (casirivimab/imdevimab and sotrovimab) are available in Italy. Therefore, we aimed to evaluate the presence of risk factors associated with disease progression. We conducted a retrospective cohort study, including all patients with a confirmed diagnosis of SARS-CoV-2 evaluated between 01/01/2022 ad 10/05/2022 by our Unit of Infectious Diseases in Sassari. We defined disease progression as the necessity of starting O2 therapy. According to AIFA (Italian Medicines Agency) indications, preventive treatment was prescribed in patients with recent symptoms onset (≤five days), no need for oxygen supplementation, and risk factors for disease progression. Subgroup differences in quantitative variables were evaluated using Student’s t-test. Pearson chi-square or Fisher’s exact tests were used to assess differences for qualitative variables. Multivariate logistic regression modelling was performed to determine factors associated with progression. A two-tailed p-value less than 0.05 was considered statistically significant. All statistical analyses were performed with STATA version 17 (StataCorp, College Station, TX, USA). We included 1145 people with SARS-CoV-2 diagnosis, of which 336 (29.3%) developed severe disease with oxygen supplementation. In multivariate logistic regression analysis, age, dementia, haematologic tumors, heart failure, dyspnoea or fever at first evaluation, having ground glass opacities or consolidation at the first CT scan, and bacteria coinfection were associated with an increased risk of disease progression. Vaccination (at least two doses) and early treatment with antiviral or monoclonal antibodies were associated with a lower risk of disease progression. In conclusion, our study showed that vaccination and early treatment with antiviral and/or monoclonal antibodies significantly reduce the risk of disease progression. Full article

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10 pages, 627 KiB

Open AccessArticle

Rildo: Real-World Multicenter Study on the Effectiveness and Safety of Single-Tablet Regimen of Dolutegravir plus Rilpivirine in Treatment-Experienced People Living with HIV

by Carmen Hidalgo-Tenorio, David Vinuesa, Coral García-Vallecillos, Leopoldo Muñoz-Medina, Sergio Sequera, Rosario Javier, Miguel Ángel López-Ruz, Svetlana Sadyrbaeva-Dolgova and Juan Pasquau

Viruses 2022, 14(12), 2626; https://doi.org/10.3390/v14122626 - 25 Nov 2022

Cited by 4 | Viewed by 1490

Abstract

Two-drug regimens (2DRs) are emerging in clinical practice guidelines as treatment option for both naive and treatment-experienced people living with HIV (PLHIV). Objectives: To determine the real-life effectiveness of 2DR with 25 mg RPV plus 50 mg DTG in a single-tablet regimen (RPV/DTG [...] Read more.

Two-drug regimens (2DRs) are emerging in clinical practice guidelines as treatment option for both naive and treatment-experienced people living with HIV (PLHIV). Objectives: To determine the real-life effectiveness of 2DR with 25 mg RPV plus 50 mg DTG in a single-tablet regimen (RPV/DTG_STR) and its impact on viral and immune status, lipid profile, and inflammatory markers. Methods: This observational study included 291 treatment-experienced PLHIV, starting 2DR with RPV/DTG_STR between 29 January 2019 and 2 February 2022, who were followed up for at least six months. Participants gave verbal informed consent for the switch in antiretroviral therapy (ART) to RPV/DTG_STR. Results: The mean age of the 291 participants was 51.3 years; 77.7% were male; and 42.9% were in the AIDS stage with a CD4 nadir of 283.5 ± 204.6 cells/uL. The median time since HIV diagnosis was 19.7 years (IQR: 10.6–27). Before 2DR, patients received a median of five ART lines (IQR: 3–7) for 22.2 years (IQR: 14–26), with 34.4% (n = 100) receiving a three-drug regimen (3DR), 31.3% (n = 91) receiving monotherapy, and 34.4% (n = 100) receiving 2DR. The median time on RPV/DTG_STR was 14 months (IQR: 9.5–21); 1.4% were lost to the follow-up. Effectiveness was 96.2% by intention-to-treat (ITT) analysis, 97.5% by modified ITT, and 99.3% by per-protocol analysis. Virological failure was observed in 0.69%, blips in 3.5%, and switch to another ART in 1.4%. The mean lipid profile improved, with reductions in TC/HDLc ratio (3.9 ± 0.9 vs. 3.6 ± 0.9; p = 0.0001), LDLc (118.3 ± 32.2 mg/dL vs. 106.2 ± 29.8 mg/dL, p = 0.0001), TG (130.9 ± 73.9 mg/dL vs. 115.9 ± 68.5 mg/dL, p = 0.0001), and CD4/CD8 ratio increase (0.99 ± 0.58 vs. 1.01 ± 0.54; p = 0.0001). The cost-effectiveness of 2DR with RPV/DTG_STR was similar to that of DTG/3TC and superior to those of BIC/TAF/FTC and DRV/c/TAF/FTC, with higher virological suppression and lower annual costs. Conclusions: The switch to RPV plus DTG in STR is a cost-effective, long-lasting, and robust strategy for PLHIV, with a very long experience of treatment, which improves the lipid profile without affecting inflammatory markers. Full article

(This article belongs to the Special Issue Efficacy and Safety of Antiviral Therapy)

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Open AccessArticle

Real-World Effectiveness, Tolerability, and Safety of Dolutegravir/Lamivudine in Korea

by Ki Hyun Lee, Jinnam Kim, Jung Ah Lee, Chang Hyup Kim, Jin Young Ahn, Su Jin Jeong, Nam Su Ku, Jun Yong Choi, Joon-Sup Yeom, Young Goo Song and Jung Ho Kim

Viruses 2022, 14(11), 2558; https://doi.org/10.3390/v14112558 - 18 Nov 2022

Cited by 3 | Viewed by 1544

Abstract

Most studies on the real-world effectiveness and safety of dolutegravir/lamivudine (DTG/3TC) have been conducted in Western countries, and Asian reports are lacking. We evaluated the effectiveness and safety of DTG/3TC in Korean adult people living with HIV (PLWH). This retrospective study was conducted [...] Read more.

Most studies on the real-world effectiveness and safety of dolutegravir/lamivudine (DTG/3TC) have been conducted in Western countries, and Asian reports are lacking. We evaluated the effectiveness and safety of DTG/3TC in Korean adult people living with HIV (PLWH). This retrospective study was conducted from July 2020 to July 2022 at a tertiary hospital in Korea. Those who were followed up for more than 12 months were included. We analyzed the baseline characteristics, effectiveness, resistant profiles, body weights, metabolic parameters, and safety of DTG/3TC treatment in 151 PLWH, dividing them into the treatment-naïve group and the switching group. The median DTG/3TC treatment durations in the treatment-naïve and switching groups were 507.5 and 525.0 days. In the treatment-naïve group, the viral RNA titer was undetectable at 6 and 12 months in 95% of patients. In the switching group, virologic suppression was well-maintained. Meanwhile, the creatinine levels were slightly elevated in both groups compared to baseline. Five participants complained of mild side effects, such as indigestion, constipation, diarrhea, and fatigue. However, no patient stopped treatment during the follow-up period. Since there was no virological failure or serious complications observed in this study, DTG/3TC may be a good treatment option for PLWH in Korea. Full article

(This article belongs to the Special Issue Efficacy and Safety of Antiviral Therapy)

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