Antivirals against Monkeypox (Mpox) in Humans: An Updated Narrative Review.

As of 29 August 2023, a total of 89,596 confirmed cases of Mpox (monkeypox) have been documented across 114 countries worldwide, with 157 reported fatalities. The Mpox outbreak that transpired in 2022 predominantly affected young men who have sex with men (MSM). While most cases exhibited a mild clinical course, individuals with compromised immune systems, particularly those living with HIV infection and possessing a CD4 count below 200 cells/mm3, experienced a more severe clinical trajectory marked by heightened morbidity and mortality. The approach to managing Mpox is primarily symptomatic and supportive. However, in instances characterized by severe or complicated manifestations, the utilization of antiviral medications becomes necessary. Despite tecovirimat's lack of official approval by the FDA for treating Mpox in humans, a wealth of positive clinical experiences exists, pending the outcomes of ongoing clinical trials. Brincidofovir and cidofovir have also been administered in select cases due to the unavailability of tecovirimat. Within the scope of this narrative review, our objective was to delve into the clinical attributes of Mpox and explore observational studies that shed light on the utilization of these antiviral agents.

Prevalence and Risk Factors for Poor Sleep Quality in People Living with HIV: Preliminary Observations from an HIV Outpatient Clinic.

INTRODUCTION: Sleep disorders have been reported in individuals living with HIV (PLWH), with a prevalence rate of over 50%. The main risk factors contributing to the development of sleep disturbances are not yet fully understood. We investigate the prevalence and risk factors associated with poor sleep quality in a population of PLWH who are receiving antiretroviral therapy (ART). METHODS: The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate sleep quality in PLWH attending our HIV Outpatient Clinic between October 2022 and April 2023. All subjects with a PSQI score > 5 were considered bad sleepers. A logistic regression analysis was carried out to assess risk factors associated with a PSQI score > 5. RESULTS: A total of 132 PLWH (78% males) who received ART for at least one month were included in this observational study. The median age was 56 (IQR 47-61). Among all, 41 (31%) had a history of AIDS, and 95 (72%) were receiving an INSTI-based ART. The study population was divided into two groups: PSQI ≤ 5 (90; 68.2%) and PSQI > 5 (42; 31.8%). A lower BMI and the use of bictegravir in the current ART were associated with a PSQI score ≤ 5. In the multivariate analysis, the use of a bictegravir-based ART remained the only factor associated with better sleep quality (OR 0.17; p = 0.0222). No further associations between sleep disturbances and other epidemiological and clinical features were found. CONCLUSION: In this real-life scenario, poor sleep quality was observed in 31% of the cases, primarily among individuals with higher BMI. In addition, bictegravir users might seem to have a lower likelihood of experiencing poor sleep quality.

Real-life comparison of mortality in patients with SARS-CoV-2 infection at risk for clinical progression treated with molnupiravir or nirmatrelvir plus ritonavir during the Omicron era in Italy: a nationwide, cohort study.

Background: Comparative data on mortality in COVID-19 patients treated with molnupiravir or with nirmatrelvir plus ritonavir are inconclusive. We therefore compared all-cause mortality in community-dwelling COVID-19 patients treated with these drugs during the Omicron era. Methods: Data collected in the nationwide, population-based, cohort of patients registered in the database of the Italian Medicines Agency (AIFA) were used. To increase completeness of the recorded deaths and date correctness, a cross-check with the National Death Registry provided by the Ministry of the Interior was performed. We included in this study all patients infected by SARS-CoV-2 treated within 5 days after the test date and symptom onset between February 8 and April 30, 2022. All-cause mortalities by day 28 were compared between the two treatment groups after balancing for baseline characteristics using weights obtained from a gradient boosting machine algorithm. Findings: In the considered timeframe, 17,977 patients treated with molnupiravir and 11,576 patients with nirmatrelvir plus ritonavir were included in the analysis. Most patients (25,617/29,553 = 86.7%) received a full vaccine course including the booster dose. A higher crude incidence rate of all-cause mortality was found among molnupiravir users (51.83 per 100,000 person-days), compared to nirmatrelvir plus ritonavir users (22.29 per 100,000 person-days). However, molnupiravir-treated patients were older than those treated with nirmatrelvir plus ritonavir and differences between the two populations were found as far as types of co-morbidities were concerned. For this reason, we compared the weight-adjusted cumulative incidences using the Aalen estimator and found that the adjusted cumulative incidence rates were 1.23% (95% CI 1.07%-1.38%) for molnupiravir-treated and 0.78% (95% CI 0.58%-0.98%) for nirmatrelvir plus ritonavir-treated patients (adjusted log rank p = 0.0002). Moreover, the weight-adjusted mixed-effect Cox model including Italian regions and NHS centers as random effects and treatment as the only covariate confirmed a significant reduced risk of death in patients treated with nirmatrelvir plus ritonavir. Lastly, a significant reduction in the risk of death associated with nirmatrelvir plus ritonavir was confirmed in patient subgroups, such as in females, fully vaccinated patients, those treated within day 2 since symptom onset and patients without (haemato)-oncological diseases. Interpretation: Early initiation of nirmatrelvir plus ritonavir was associated for the first time with a significantly reduced risk of all-cause mortality by day 28 compared to molnupiravir, both in the overall population and in patient subgroups, including those fully vaccinated with the booster dose. Funding: This study did not receive funding.

Oral antivirals against Sars-CoV-2 in multiple myeloma outpatients: a case series.

Recently, the therapeutic armamentarium against Sars-CoV-2 has been enriched with oral antivirals that can be used in the early phases of covid-19. Real-life data on their efficacy in multiple myeloma (Mm) outpatients with mild-to-moderate covid-19 are lacking. We described the clinical outcomes at 30 days in Mm subjects with covid-19 treated with oral antivirals. Nirmatrelvir/r was prescribed in 10 subjects whereas molnupiravir in 5. Despite two hospitalizations were reported, we did not observe deaths due to covid-19 in this vulnerable group. Our preliminary observations reinforce the early use of oral antivirals as a useful means to contain severe covid-19 in high-risk patients such as Mm individuals characterized by an impaired immune response.

Cidofovir for treating complicated monkeypox in a man with acquired immune deficiency syndrome.

In July 23, the World Health Organization (WHO) declared monkeypox (MPX) a global health emergency of international concern given its rapid spread. So far, most current MPX outbreaks have involved young men who have sex with men (MSM), although with overall mild, self-limiting clinical manifestations. We aim to describe the case of an HIV positive young MSM whose status of immune compromission probably contributed to a more severe clinical course of MPX disease, thus requiring hospitalization and antiviral treatment. He was effectively treated with Cidofovir that may be considered as a valuable component of a multi-faceted management of severe MPX.

Efficacy and safety of oral antivirals in individuals aged 80 years or older with mild-to-moderate COVID-19: preliminary report from an Italian Prescriber Center.

Introduction: Molnupiravir and Nirmatrelvir/ritonavir( r), have demonstrated to prevent the progression to severe COVID-19 in high-risk individuals. Real life data are lacking in the elderly. Methods: All consecutive individuals aged ≥80 years with confirmed COVID-19 and mild-to-moderate illness who received an oral antiviral prescription between 11th January and 31st May 2022 were included in this retrospective single-centre study. The aim was to assess safety and effectiveness of oral antivirals in individuals ≥80 years with mild to moderate COVID-19. Results: A total of 168 subjects ≥80 years were included. Molnupiravir was prescribed in 147 (87.5%) subjects whereas Nirmatrelvir/r in 21 (12.5%); 16 (9.5%) experienced at least one adverse event. Overall, 21 (12.5%) hospitalizations and five deaths were reported at 28 days. At multivariate analysis male sex (OR=4.196, 95% CI=1.479-11.908; p=0.007), a moderate illness at time of prescription (OR=10.946, 95% CI=2.857-41.395; p=0.0005) and a greater number of days from the onset of symptoms to the therapy (OR=2.066, 95% CI=1.285-3.322; p=0.0027) were associated with hospitalization and/or death. Conclusion: In this real-life setting, including older individuals' hospitalizations and mortality at 28 days remained low thanks to the prompt initiation of oral antiviral therapy. The use of oral antivirals can play a significant role in reducing healthcare costs and ensuring benefits among the elderly population.

Early Access to Oral Antivirals in High-Risk Outpatients: Good Weapons to Fight COVID-19.

INTRODUCTION: Molnupiravir and Nirmatrelvir/r (NMV-r) have been proven to reduce severe Coronavirus Disease 2019 (COVID-19) in unvaccinated high-risk individuals. Data regarding their impact in fully vaccinated vulnerable subjects with mild-to-moderate COVID-19 are still limited, particularly in the era of Omicron and sub-variants. METHODS: Our retrospective study aimed to compare the safety profile and effectiveness of the two antivirals in all consecutive high-risk outpatients between 11 January and 10 July 2022. A logistic regression model was carried out to assess factors associated with the composite outcome defined as all-cause hospitalization and/or death at 30 days. RESULTS: A total of 719 individuals were included: 554 (77%) received Molnupiravir, whereas 165 (23%) were NMV-r users. Overall, 43 all-cause hospitalizations (5.9%) and 13 (1.8%) deaths were observed at 30 days. A composite outcome occurred in 47 (6.5%) individuals. At multivariate analysis, male sex [OR 3.785; p = 0.0021], age ≥ 75 [OR 2.647; p = 0.0124], moderate illness [OR 16.75; p < 0.001], and treatment discontinuation after medical decision [OR 8.148; p = 0.0123] remained independently associated with the composite outcome. CONCLUSIONS: No differences between the two antivirals were observed. In this real-life setting, the early use of both of the oral antivirals helped limit composite outcome at 30 days among subjects who were at high risk of disease progression.

Monkeypox Virus Infections in Southern Italy: Is There a Risk for Community Spread?

The ongoing outbreak of the Monkeypox virus (MPXV) is characterized by sustained human-to-human transmission, particularly among men who have sex with men (MSM). The aim of the study was to describe the characteristics of the MPXV infection identified in Southern Italy. Clinical samples for each suspected case identified from 1 June to 1 August 2022 were tested for MPXV, and whole-genome sequencing (WGS) was performed on two strains. Ten cases were identified: eight were young adult males, including six MSMs, and two were female. Nine subjects reported recent sexual exposure. One female subject without sexual exposure only reported attendance at a social gathering. Overall, 7 of 10 skin lesion samples had a high viral load of MPXV DNA, and 6/9 whole blood samples and 6/8 nasopharyngeal swab samples also tested positive. The analyzed sequences belonged to Clade 3, lineage B.1, and B.1.5, respectively. Despite this recent multinational outbreak of MPXV cases having revealed a high proportion of cases occurring among MSM, the identification of cases among heterosexual subjects and in a female subject without sexual risk factors should raise awareness among clinicians about the possible spread of MPXV in the general population.

A Cluster of Cryptic Plasmodium falciparum Malaria in African Migrants in Southern Italy, October 2017.

Background: Italy was declared malaria free by the World Health Organization in 1970. Despite this, nonimport malaria cases are on the increase in Italy and throughout the Mediterranean area. In Italy, in the period between 2011 and 2015, seven cases of locally acquired malaria have been reported, including one introduced case of Plasmodium vivax; moreover, the last certain case of introduced malaria (by P. vivax) has been reported in Tuscany in 1997. No case of introduced malaria from Plasmodium falciparum has been reported in Italy since 1970. Case Presentation: A cluster of four cryptic P. falciparum malaria cases were ascertained in migrant farm workers (three from Morocco and one from Sudan) in Apulia (southern Italy) with clinical onset between September 20 and 27, 2017. None of the patients reported a history of a recent trip to malaria-endemic areas or hospitalization or other risk factors. Typing of malaria was also confirmed using molecular biology methods in two different laboratories. There were no cases of severe malaria in our four patients, and only one in need of transfusion. All patients were discharged cured after being treated with mefloquine due to the unavailability of other antimalarials. Conclusions: In recent years, numerous reports of locally acquired malaria have been made in southern Europe. The cases described in this article represent the first cluster of malaria caused by P. falciparum in Europe. Today, clinical presentation in the diagnosis of malaria is more important than ever, since epidemiological criterion cannot be considered unfailing. The mode of transmission has not been proven and further biological and entomological studies are necessary to define our case as cryptic or confirm the presence of mosquitoes capable of transmitting P. falciparum and/or the capacity of Anopheles labranchiae, An. superpictus, or An. plumbeus to transmit it on Italian territory.