Impact of monotherapy on HIV-1 reservoir, immune activation, and co-infection with Epstein-Barr virus

Abstract Objectives Although monotherapy (mART) effectiveness in maintaining viral suppression and CD4 cell count has been extensively examined in HIV-1-infected patients, its impact on HIV-1 reservoir, immune activation, microbial translocation and co-infection with Epstein-Barr Virus (EBV) is unclear. Methods This retrospective study involved 32 patients who switched to mART; patients were studied at baseline, 48 and 96 weeks after mART initiation. Thirty-two patients who continued combined antiretroviral therapy (cART) over the same period of time were included in the study. Markers of HIV-1 reservoir (HIV-1 DNA and intracellular HIV-1 RNA) were quantified by real-time PCR. Markers of T-(CD3(+)CD8(+)CD38(+)) and B-(CD19(+)CD80/86(+) and CD19(+)CD10-CD21(low)CD27(+)) cell activation were evaluated by flow cytometry. Plasma levels of microbial translocation markers were quantified by real-time PCR (16S ribosomal DNA and mitochondrial [mt] DNA) or by ELISA (LPS and sCD14). EBV was typed and quantified by multiplex real-time PCR. Results At baseline, no differences were found between mART and cART groups. Three (10%) mART-treated patients had a virological failure vs none in the cART group. Levels of HIV-1 DNA, intracellular HIV-1 RNA and EBV-DNA remained stable in the mART group, while decreased significantly in the cART group. Percentages of T-and B-activated cells significantly increased in the mART-treated patients, while remained at low levels in the cART-treated ones (p = 0.014 and p<0.001, respectively). Notably, levels of mtDNA remained stable in the cART group, but significantly rose in the mART one (p<0.001). Conclusions Long-term mART is associated with higher levels of T-and B-cell activation and, conversely to cART, does not reduce the size of HIV-1 reservoir and EBV co-infection

FOLLOW-UP A BREVE-LUNGO TERMINE DELL’INFEZIONE NEUROINVASIVA DA WEST NILE VIRUS NEL NORD-EST ITALIA

Premessa La “West Nile Fever” è una malattia provocata West Nile virus (WNV), Flavivirus isolato nel 1937 nel distretto West Nile (Uganda) e diffuso in Africa, Asia occidentale, Europa, Australia e America. La maggior parte delle infezioni da WNV, restano asintomatiche, mentre circa il 20% presenta febbre, cefalea, nausea, vomito, linfadenopatia, rash cutaneo. Meno dell’1% delle persone sintomatiche sviluppa una forma neuro-invasiva severa (WNND) caratterizzata da quadri meningitici, encefalitici, poliomielitici. Nonostante le numerose acquisizioni riguardanti le caratteristiche cliniche della fase acuta di malattia, pochi sono i dati sul “long-term follow-up” della malattia neuro invasiva e le sue sequele funzionali. Obiettivo dello studio Analizzare l’andamento clinico nel breve-lungo periodo dei soggetti ricoverati presso le Malattie Infettive di Rovigo e Ferrara (Agosto 2008-Dicembre 2010) e dimessi con diagnosi di WNND. Sono stati valutati 14 pazienti con i seguenti parametri: 1) caratteristiche demografiche: età, sesso, luogo di residenza, stagionalità; 2) comorbidità significative per WNND; 3) caratteristiche cliniche: manifestazioni all’esordio, durante la degenza e complicanze; 4) diagnosi: metodi diagnostici, tempo intercorso tra ricovero e diagnosi (latenza diagnostica); 5) outcome a breve e a lungo termine. I pazienti sono stati suddivisi in 2 gruppi: quadri di meningo-encefalite (Gruppo 1; 7 casi) e di meningo-encefalite associata a paralisi flaccida acuta (Gruppo 2; 7 casi). Risultati Dei 14 pazienti ricoverati, 10 (64%) erano uomini e 4 (36%) donne; età mediana 70,5 a (range 47-84); 68 a nel Gruppo 1, 73 a nel gruppo 2. 13 soggetti erano italiani,1 Rumeno. Tutti i soggetti presentavano comorbidità per WND. Complessivamente, i ricoveri sono avvenuti tra agosto e dicembre (5 ad Agosto, 8 a Settembre, 1 a Dicembre). La durata media di ospedalizzazione è stata significativamente diversa fra il 1° e 2° Gruppo (36 vs 47 gg) come pure vi è stata una differenza significativa nel numero delle complicanze ( > nel Gruppo 2). In un follow-up di 32 mesi (media, 1-52) si sono verificati 7 decessi; 3 (21%) durante la degenza, 4 (28%) dopo la dimissione (range 7 giorni-12 mesi), con un tasso di letalità complessivo del 43%. L’età (>64 a) è risultato l’ unico fattore significativamente correlato alla mortalità. La Tabella 1 mostra gli “outcome” a breve e lungo termine di tutti i pazienti. Conclusione La malattia neuro invasiva da WNV è una patologia ad elevata mortalità, sia in fase acuta che cronica, gravata dallo sviluppo di numerose sequele neurologiche, più marcate e debilitanti nei pazienti con paralisi flaccida acuta che nel lungo termine, nella nostra casistica, non hanno mostrato alcun recupero delle funzioni fisiche e perdita dell’autosufficienza. In accordo con la letteratura, la popolazione anziana, di sesso maschile e con anamnesi positiva per patologie pregresse, si è dimostrata essere quella più suscettibile alla malattia neuro invasiva da WNV

Rapid Antigen Test LumiraDxTM vs. Real Time Polymerase Chain Reaction for the Diagnosis of SARS-CoV-2 Infection: A Retrospective Cohort Study

Background: Real time reverse transcription polymerase chain reaction (real time RT-PCR) testing is the gold standard for the diagnosis of SARS-CoV-2 infections. However, to expand the testing capacity, new SARS-CoV-2 rapid antigen tests (Ag-RDTs) have been implemented. Ag-RDTs are more rapid, but less reliable in terms of sensitivity, and real-life data on their performance in comparison with the real time RT-PCR test are lacking. Methods: We aimed at assessing the diagnostic performance of the third-generation antigenic swab LumiraDx (TM) compared with real time RT-PCR in a retrospective cohort study at the Infectious Diseases Unit of Padua. All of the patients who were consecutively tested for SARS-CoV-2 in our centre (by both real time RT-PCR and Ag-RTD LumiraDx(TM)) from 19 January to 30 May 2021, were included. Cycle-threshold (Ct) values of positive real time RT-PCR were recorded as well as the number of days from symptoms' onset to testing. Results: Among the 282 patients included, 80.9% (N = 228) tested positive to real time RT-PCR, and among these, 174 tested positive also to LumiraDx (TM). Compared with real time RT-PCR, which is considered as the gold standard for the assessment of the presence/absence of SARS-CoV-2 infection, LumiraDx (TM) showed an overall sensitivity of 76.3% and specificity of 94.4%. Sensitivity increased to 91% when testing was performed <10 days from symptoms' onset, and to 95% when considering Ct < 25. Multivariable binomial logistic regression showed that false negative LumiraDx (TM) results were significantly associated with high Ct values, and with further testing from symptoms' onset. Conclusions: The results of our study suggested that the LumiraDx (TM) SARS-CoV-2 antigen assay may be appropriate for the detection of SARS-CoV-2 infection, especially in its early phase when the test largely meets the performance requirements of the European Centre for Disease Prevention and Control (ECDC)

COVID-19 Vaccination Limits Systemic Danger Signals in SARS-CoV-2 Infected Patients

Vaccination with an mRNA COVID-19 vaccine determines not only a consistent reduction in the risk of SARS-CoV-2 infection but also contributes to disease attenuation in infected people. Of note, hyperinflammation and damage-associated molecular patterns (DAMPs) have been clearly associated with severe illness and poor prognosis in COVID-19 patients. In this report, we revealed a significant reduction in the levels of IL-1ß and DAMPs molecules, as S100A8 and High Mobility Group Protein B1 (HMGB1), in vaccinated patients as compared to non-vaccinated ones. COVID-19 vaccination indeed prevents severe clinical manifestations in patients and limits the release of systemic danger signals in SARS-CoV-2 infected people

Viro-Immunological, Clinical Outcomes and Costs of Switching to BIC/TAF/FTC in a Cohort of People Living with HIV: A 48-Week Prospective Analysis

To date, therapeutic switches are performed to reduce and prevent toxicity, improve adherence, promote virological control, and save costs. Drug switches are a daily challenge in the management of people living with HIV (PLWH), especially in those with multiple comorbidities and on polypharmacy. The objectives of this prospective analysis were: (I) to evaluate the viro-immunological efficacy of BIC/FTC/TAF in a cohort of PLWH who switched to this regimen from any other previous, at the Infectious and Tropical Diseases Unit of the Padua University Hospital; (II) to assess the impact on body weight, lipids, and renal function parameters at week 48; and (III) to evaluate daily costs changes, adherence, and the rate and causes of discontinuation of the regimen. We included all adult PLWH who switched to BIC/FTC/TAF from 1 February 2020 to 31 October 2021. We collected demographic, clinical, and laboratory data at baseline and week 48 after the switch. In addition, the estimated cART-related cost changes over the follow-up period were calculated. Over the study period, 290 individuals who switched to BIC/FTC/TAF, 76.9% were males, with a median age of 52 years, and 94.8% had an undetectable baseline HIV viremia. After a median time of 35 days (IQR: 1&ndash;55), 41 (14.1%) individuals discontinued the regimen. Factors significantly associated with discontinuation were switching from dual regimens, and neurological disorders. At week 48, we detected a significant increase in body weight, BMI, CD4 T-cell count, and CD4/CD8 ratio, and a significant reduction in triglycerides and costs; all patients had undetectable HIV RNA. Our results showed that switching to BIC/FTC/TAF may favor slightly immunological recovery and cost saving (&minus;4.2 EUR/day from baseline to week 48, equivalent to a mean saving of 1533 EUR/year/person). The reduction in triglycerides does not appear to be clinically relevant, even if statistically significant, nor do both the increase in body weight and BMI (+1 kg and +0.29 BMI, respectively) and the increase in CD4 T-cell count (+45 cells/mmc). Further studies are needed to confirm our results

Prolonged SARS-CoV-2-RNA Detection from Nasopharyngeal Swabs in an Oncologic Patient: What Impact on Cancer Treatment?

The pandemic of SARS-CoV-2 is a serious global challenge affecting millions of people worldwide. Cancer patients are at risk for infection exposure and serious complications. A prompt diagnosis of SARS-CoV-2 infection is crucial for the timely adoption of isolation measures and the appropriate management of cancer treatments. In lung cancer patients the symptoms of infection 19 may resemble those exhibited by the underlying oncologic condition, possibly leading to diagnostic overlap and delays. Moreover, cancer patients might display a prolonged positivity of nasopharyngeal RT-PCR assays for SARS-CoV-2, causing long interruptions or delay of cancer treatments. However, the association between the positivity of RT-PCR assays and the patient’s infectivity remains uncertain. We describe the case of a patient with non-small cell lung cancer, and a severe ab extrinseco compression of the trachea, whose palliative radiotherapy was delayed because of the prolonged positivity of nasopharyngeal swabs for SARS-CoV-2. The patient did not show clinical symptoms suggestive of active infection, but the persistent positivity of RT-PCR assays imposed the continuation of isolation measures and the delay of radiotherapy for over two months. Finally, the negative result of SARS-CoV-2 viral culture allowed us to verify the absence of viral activity and to rule out the infectivity of the patient, who could finally continue her cancer treatment