Efficacy and Safety of Nirmatrelvir/Ritonavir, Molnupiravir, and Remdesivir in a Real-World Cohort of Outpatients with COVID-19 at High Risk of Progression: The PISA Outpatient Clinic Experience.

INTRODUCTION: Different antivirals are available for the treatment of outpatients with COVID-19. Our aim was to describe a real-world experience of outpatient management of COVID-19 subjects at high risk of progression. METHODS: This prospective observational study conducted in the University Hospital of Pisa (January 2022-July 2022) included consecutive COVID-19 outpatients with at least one risk factor for disease progression. Patients received nirmatrelvir/ritonavir, molnupiravir, or 3-day remdesivir, according to the Italian Medicines Agency (AIFA) indications. All patients were followed up until 30 days from the first positive nasopharyngeal swab. The primary endpoint was a composite of death or hospitalization. Secondary endpoints were occurrence of adverse events and a negative test within 10 days from the first positive test. Multivariable analysis was performed to identify factors associated with death or hospitalization. RESULTS: Overall, 562 outpatients were included: 114 (20.3%) received molnupiravir, 252 (44.8%) nirmatrelvir/ritonavir, and 196 (34.9%) 3-day remdesivir. The composite endpoint occurred in 2.5% of patients and was more frequent in patients treated with remdesivir (5.1%) compared with molnupiravir (1.8%) or nirmatrelvir/ritonavir (0.8%, ANOVA among groups p = 0.012). On multivariable Cox regression analysis, presence of ≥ 3 comorbidities, hematological disease, gastrointestinal symptoms, and each-day increment from symptoms onset were factors associated with death or hospitalization, while antiviral treatment was not a predictor. Adverse events occurred more frequently in the nirmatrelvir/ritonavir group (49.2%). Nirmatrelvir/ritonavir compared with remdesivir was associated with a higher probability of having a negative test within 10 days from the first positive one. CONCLUSION: Death or hospitalization did not differ among high-risk COVID-19 outpatients treated with currently available antivirals. Safety and time to a negative test differed among the three drugs.

Impact of Exercise-Induced Pulmonary Hypertension on Right Ventricular Function and on Worsening of Cardiovascular Risk in HIV Patients.

Background and Aim: Exercise-induced pulmonary hypertension (ExPH) predicts clinical outcomes, such as all-cause mortality and cardiovascular (CV) hospitalizations, in patients with dyspnea on effort. We investigated its prognostic significance in human immunodeficiency virus (HIV)-affected patients. Methods: In 52 consecutive HIV patients with either low (n = 47) or intermediate probability (n = 5) of PH at rest, we evaluated­at time 0 and after 2 years­the prognostic determinants of CV risk, according to the 2015 European Society of Cardiology (ESC)/European Respiratory Society (ERS) Guidelines. Patients were classified with or without ExPH at stress echocardiography (ESE) and cardiopulmonary exercise test (CPET). We then related ExPH at time 0 with clinical worsening (CV risk score increase >20% after 2 years). Results: Right ventricle (RV) systolic function was significantly reduced in patients with ExPH compared to those without ExPH at CPET. This also occurred in patients with intermediate/high probability compared to those with low probability of ExPH at ESE. The former exhibited worse values of TAPSE and FAC (p < 0.001 and p = 0.01, respectively). A significantly higher proportion of patients with ExPH (CPET) or with intermediate/high probability of ExPH (ESE) had higher sPAP (p < 0.001), mPAP (p = 0.004) and higher TRV (p = 0.006), as well as higher right atrial area (p < 0.001) and indexed right atrial volume (p = 0.004). Total pulmonary vascular resistance (expressed by the ratio between TRV and the velocity-time integral at the level of the right ventricular outflow tract) was higher both in patients with ExPH and in those with intermediate/high probability of ExPH (p < 0.001). Patients with intermediate/high probability of ExPH at ESE showed a trend (p = 0.137) towards clinical worsening compared to those with low probability of ExPH. No patients with low probability of ExPH had a >20% increased CV risk score after 2 years. We found an association between higher NT-proBNP and the presence or intermediate/high probability of ExPH after 2 years (p = 0.048 at CPET, p = 0.033 at ESE). Conclusions: The assessment of ExPH may predict a trend of increasing CV risk score over time. If confirmed at a longer follow-up, ExPH could contribute to better risk stratification in HIV patients.

Recrudescence of Plasmodium falciparum malaria 5 years after treatment in an HIV migrant: a case report with a peculiar presentation.

In the last two decades, several cases of delayed-onset malaria in migrants from endemic areas were reported. The decrease of acquired immunity over time, often enhanced by immune suppression, represents a possible underlying mechanism for recrudescence. Here we describe a case of Plasmodium falciparum malaria occurring five years after exposure in a patient infected with human immunodeficiency virus, originating from Ivory Coast. Peculiarly, bilateral subsegmental pulmonary embolism in the absence of deep venous thrombosis was also detected, requiring anticoagulant therapy. Treatment with dihydroartemisinin/piperaquine was followed by clearance of trophozoites and the patient was discharged home.

Exercise-Induced Pulmonary Hypertension Is Associated with High Cardiovascular Risk in Patients with HIV.

Background and Aim: Pulmonary hypertension (PH) at rest can be preceded by the onset of exercise-induced PH (ExPH). We investigated its association with the cardiovascular (CV) risk score in patients with human immunodeficiency virus (HIV). Methods: In 46 consecutive patients with HIV with low (n = 43) or intermediate (n = 3) probability of resting PH, we evaluated the CV risk score based on prognostic determinants of CV risk. Diagnosis of ExPH was made by cardiopulmonary exercise test (CPET) and exercise stress echocardiogram (ESE). Results: Twenty-eight % (n = 13) of the enrolled patients had ExPH at both CPET and ESE, with good agreement between the two methods (Cohen's kappa = 0.678). ExPH correlated directly with a higher CV score (p < 0.001). Patients with a higher CV score also had lower CD4+ T-cell counts (p = 0.001), a faster progression to acquired immunodeficiency syndrome (p < 0.001), a poor immunological response to antiretroviral therapy (p = 0.035), higher pulmonary vascular resistance (p = 0.003) and a higher right atrial area (p = 0.006). Conclusions: Isolated ExPH is associated with a high CV risk score in patients with HIV. Assessment of ExPH may better stratify CV risk in patients with HIV.

Post-transplant liver graft schistosomiasis in a migrant from Sub-Saharan Africa.

We report a case of post-transplant liver graft infection with Schistosoma spp in a migrant from sub-Saharan Africa transplanted for HBV-related cirrhosis and with undiagnosed schistosomiasis pre-transplantation. The occurrence of tropical diseases in non-endemic areas warrants screening protocols for organ donors and recipients with a history of exposure in endemic areas.

Rhabdomyolysis in an HIV-infected patient following coronary angiography: case report and literature review.

Rhabdomyolysis is a rare, but possible, complication of combination antiretroviral therapy (cART). We report a unique case of an HIV-positive patient on cART who came to our attention for suspected ischaemic heart disease. Coronary angiography was carried out and complicated in the following days by rhabdomyolysis. We discuss the possible links between rhabdomyolysis, iodinated contrast media and HAART.