Case Report: Intravenous Pentamidine Rescue Treatment for Active Chronic Visceral Leishmaniasis in an HIV-1 Infected Patient.

The management of visceral leishmaniasis (VL) in HIV-infected patients is complex because of high mortality rates, toxic drug-related side effects, and a high risk of treatment failure and relapse. We report a case of active chronic VL in an HIV-1-infected woman presenting multiple secondary VL episodes over 7 years leading to massive splenomegaly and blood transfusion-dependent anemia despite several treatment courses and secondary prophylaxis. The patient was finally successfully treated with rescue treatment based on intravenous pentamidine. Twenty months after discontinuation of pentamidine the patient presented complete clinical and parasitological response. In patients with active chronic VL, treatment with intravenous pentamidine can be effective and should be considered as rescue treatment.

Soccer in the time of COVID-19: 1 year report from an Italian top league club, March 2020-February 2021.

We report the events of an Italian top league soccer club that took place in 1 year (from March 2020 to February 2021) at the time of coronavirus disease 2019 (COVID-19) pandemic. In early March 2020, just before sport competitions were called off due to the national lockdown in Italy, the team, which included 27 players and 26 staff at the time, faced a COVID-19 outbreak, with 16 confirmed and seven probable cases, including three staff members who had to be hospitalised. In May 2020, at the resumption of the training sessions, a high prevalence of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G positivity (35/53, 66%) was detected among the members of the group. In the following months, sport activities were organised behind closed doors with stringent risk mitigation procedures in place. As of February 2021, only two new cases of SARS-CoV-2 infection were detected within the group, against more than 3500 nasopharyngeal swabs and 1000 serological tests.

High rate of sustained virological response with direct-acting antivirals in haemophiliacs with HCV infection: A multicenter study.

BACKGROUND AND AIMS: Chronic hepatitis C is the main co-morbidity in adult patients with haemophilia (PwH). It causes progressive liver damage leading to end-stage liver disease and/or hepatocellular carcinoma. Eradication of HCV was possible with interferon (IFN)-based regimens in the past and direct-acting antivirals (DAAs) more recently. PwH have been considered "difficult-to-treat" because of several bad predictors of response. The advent of DAAs has provided high rates of sustained virological response (SVR) despite bad prognostic factors. Here, we present the results of antiviral treatment with DAAs in PwH treated in 2 large Italian Hemophilia Treatment Centers. METHODS: PwH and chronic hepatitis C sustained by any HCV genotype were eligible for therapy with DAAs, including those with compensated cirrhosis, HIV infection and/or previous failure to IFN-based antiviral therapy. Patients received DAAs for 8-24 weeks according to existing guidelines. SVR was defined as persistent negative serum HCV-RNA at 12 weeks after treatment completion (SVR12). RESULTS: Between January 2015 and November 2018, 200 patients aged 21-84 years (median: 50.5) received DAAs. HCV genotype 1 was the most prevalent (158, 79%). Forty patients (20%) were HIV positive, 56 (28%) had cirrhosis and 91 (46%) previously failed interferon-based treatment. Ribavirin was used in 70 (35%). HCV-RNA was undetectable at week 4 in 124/192 (65%) and SVR12 was achieved in 193/195 (99%). No patient had serious side effects related to DAAs. CONCLUSIONS: DAAs were safe and highly effective in PwH irrespective of HIV status, stage of liver disease severity and/or previous failure to IFN-based therapy.

Impact of the M184V Resistance Mutation on Virological Efficacy and Durability of Lamivudine-Based Dual Antiretroviral Regimens as Maintenance Therapy in Individuals With Suppressed HIV-1 RNA: A Cohort Study.

BACKGROUND: Dual therapy (DT) with boosted protease inhibitors (bPIs) plus lamivudine has been shown to be superior to bPI monotherapy in virologically suppressed patients despite previous selection of the lamivudine resistance M184V mutation. We compared the virological efficacy of lamivudine-based DT in patients with and without a history of M184V detection. METHODS: We retrospectively analyzed patients with HIV-RNA ≤50 copies/mL switching to DT with at least 1 previous resistance genotype in the ARCA database. Time to virological failure (VF; HIV-RNA ≥200 copies/mL or 2 consecutive HIV-RNA >50 copies/mL) and to treatment discontinuation (TD) was analyzed by survival analysis. RESULTS: Four hundred thirty-six patients switching to lamivudine plus bPIs (70%) or integrase inhibitors (30%) were included. Patients with M184V (n = 87) were older, had lower nadir CD4+ cell count, longer duration of antiretroviral therapy and of virologic suppression, and higher rate of hepatitis C virus infection compared with patients without M184V. The 3-year probability of remaining free from VF was 91.9% (95% confidence interval [CI], 86.6-97.2) without M184V and 87.8% (95% CI, 78.4-97.2) with M184V (P = .323). The time to TD did not differ between groups. Multivariate analysis adjusting for baseline variables differing between groups also did not detect M184V as being associated with VF or TD; however, the 3-year probability of remaining free of viral blips (isolated HIV-RNA 51-199 copies/mL) was 79.8% (95% CI, 67.8%-91.8%) with M184V vs 90.1% (95% CI, 84.0%-96.2%) without M184V (P = .016). CONCLUSIONS: Previous selection of M184V did not increase the risk of VF or TD with lamivudine-based DT but was associated with a higher probability of viral blips.

Polyomavirus microRNA in saliva reveals persistent infectious status in the oral cavity.

Current evidence suggests that Polyomavirus (PyV) microRNAs (miRNAs) circulating in biological fluids may be relevant to understanding viral persistence. Here, the expression of polyomavirus BKPyV, JCPyV, MCPyV and SV40 miRNAs in saliva was investigated to evaluate PyV prevalence/persistence in the oral cavity. PyV-DNA status and PyV-miRNA expression was examined in paired saliva and plasma samples of 100 HIV-infected patients and of 50 healthy subjects using digital droplet PCR and PyV-miRNA-5p stem-loop RT-PCR. Overall, the PyV-miRNA in saliva samples showed higher positivity (65%) than PyV-DNA (24%). In particular, the PyV-miRNA prevalence in HIV-infected patients was 66% and that in healthy subjects was 64%. The PyV-DNA prevalence values in the HIV-infected and healthy subjects were 25% and 22%, respectively. The presence of a single type of PyV-miRNA in the saliva of HIV-infected patients ranged from 14% (MCPyV) to 61% (BKPyV) and in healthy subjects ranged from 14% (SV40) to 70% (BKPyV). Moreover, the PyV-miRNA in the saliva of both HIV-infected and healthy subjects exhibited higher prevalence than that in the paired plasma samples. Notably, the saliva of the HIV-infected and healthy subjects was more frequently positive for more than one PyV-miRNA than the paired plasma samples or the PyV-DNA in the paired saliva and plasma samples. Collectively, these data suggest that additional investigations of PyV-miRNA present in saliva may be useful to shed light on their utility as a surrogate for determining viral infection.

PrEP in Italy: The time may be ripe but who's paying the bill? A nationwide survey on physicians' attitudes towards using antiretrovirals to prevent HIV infection.

Several studies have demonstrated the efficacy of the oral pre-exposure prophylaxis (PrEP) with tenofovir (with or without emtricitabine) on preventing HIV-negative partners of HIV infected patients to become infected through sexual contacts. PrEP is already available in the United States and now is approved by European Medicine Agency. In this setting we would like to gauge physicians' knowledge, acquaintance with and attitude to include PrEP in their clinical practice. A cross sectional survey was conducted among Italian physicians expert on antiretroviral therapy. Out of 146 physicians, 35% of participants declared to be familiar with PrEP but only 46% of them believed that, currently, there are not enough reasons to make it available in Italy. 51% of physicians have already been attracted to prescribe it and 63.4% have been openly asked about PrEP. The main concerns noticed were: the risk of acquire other sexual transmitted diseases (STDs) (70% of physicians feared that PrEP could favor STDs spread), the potential harmful of PrEP if not adequately implemented and, especially the risk of possible side effects if not properly used. Nevertheless, 55.9% of participants believed that Health Authorities face an ethical obligation to make PrEP available as part of the strategies to protect from HIV transmission and half of the respondents asked for further researches to better define the role for PrEP. Attitudes regarding PrEP impact on Italian National Health Organization were also very interesting: 57.5% of participants did not believe that investing in PrEP would be an appropriate use of healthcare resources, while 70.6% affirmed that PrEP's financial coverage should not be funded by the Italian National System of Health (SSN). This survey showed a high awareness of PrEP potential among Italian physicians coupled with a great deal of skepticism about how and if implementing it in clinical practice.

Chronic HBV infection in pregnant immigrants: a multicenter study of the Italian Society of Infectious and Tropical Diseases.

The aims of the study were to estimate the clinical impact of HBV infection in pregnant immigrants and their family members and to identify a useful approach to managing the healthcare of HBsAg-positive immigrants. Included in this study were 143 HBsAg-positive pregnant immigrants of the 1,970 from countries with intermediate/high HBV endemicity who delivered in 8 Italian hospitals in 2012-2013. In addition, 172 family members of 96 HBsAg-positive pregnant immigrants were tested for serum HBsAg. The median age of the 143 HBsAg-positive pregnant immigrants was 31.0±12.1 years and the length of stay in Italy 5.0±4.1 years; 56.5% were unaware of their HBsAg positivity. HBV DNA was detected in 74.5% of the pregnant immigrants, i.e., 94.3% from Eastern Europe, 72.2% from East Asia and 58.1% from Sub-Saharan Africa. HBV DNA ≥2000 IU/mL was detected in 47.8% of pregnant immigrants, associated with ALT ≥1.5 times the upper normal value in 15% of cases. Anti-HDV was detected in 10% of cases. HBsAg was detected in 31.3% of the 172 family members. All HBsAg-positive immigrants received counseling on HBV infection and its prevention, and underwent a complete clinical evaluation. The findings validate the approach used for the healthcare management of the HBsAg-positive immigrant population.

The JCPYV DNA load inversely correlates with the viral microrna expression in blood and cerebrospinal fluid of patients at risk of PML.

BACKGROUND: In light of their regulatory role, changes in the expression of Polyomavirus JC (JCPyV) microRNAs may be relevant for virus reactivation and the development of progressive multifocal leukoencephalopathy (PML). OBJECTIVES: To investigate the presence of JCPyV-DNA and JCPyV microRNA expression in clinical specimens of patients at risk for PML. STUDY DESIGN: The JCPyV-DNA and microRNA status was assessed in peripheral blood mononuclear cells (PBMCs) and plasma from 100 HIV patients, in serum and cerebrospinal fluid (CSF) from 14 HIV PML patients and in PBMCs and plasma from 50 healthy controls using Multiplex real-time PCR and JCPyV miRNA-J1-3p and -5p stem-loop RT-PCR. The JCPyV-DNA microRNA-expressing region was also sequenced. RESULTS: A positive JCPyV-DNA status was more prevalent in HIV patients (67%, 67/100) compared to healthy controls (18%, 9/50). Among these, 46% and 42% of the HIV patients and 18% and 0% of the healthy controls were positive based on PBMC and plasma determinations, respectively. PBMC JCPyV microRNA positivity was observed in 22 out of 46 (48%) JCPyV+ HIV patients and in 3 out of 9 (33%) JCPyV+ healthy controls. Moreover, JCPyV microRNAs in exosomes were found in 6 out of 100 (6%) HIV plasma samples, in 12 out of 50 (24%) healthy samples, in 6 out of 14 (43%) serum samples, and in 3 out of 5 (60%) HIV PML CSF samples. Of note, the JCPyV-DNA load was inversely correlated with expression of the viral microRNA. The JCPyV microRNA genomic expression region showed a different combination of three mutations. CONCLUSIONS: The low levels of JCPyV microRNA expression in HIV patients with high JCPyV-DNA prevalence observed in this study highlight the potential clinical relevance of JCPyV microRNAs in PML risk assessment.

Zika virus infections imported to Italy: clinical, immunological and virological findings, and public health implications.

We report the first two cases of laboratory confirmed Zika virus (ZIKV) infections imported into Italy from French Polynesia. Both patients presented with low grade fever, malaise, conjunctivitis, myalgia, arthralgia, ankle oedema, and axillary and inguinal lymphadenopathy. One patient showed leukopenia with relative monocytosis and thrombocytopenia. The diagnosis was based on ZIKV seroconversion in both cases and on ZIKV RNA detection in one patient from acute serum sample. Sera from both patients exhibited cross-reactivity with dengue virus antigens. Our immunological analysis demonstrated that recovery from ZIKV infection is associated with restoration of normal numbers of immune cells in the periphery as well as with normal function of antigen-presenting cells. ZIKV is an emerging arbovirus, which has recently spread extensively in tourist destinations on several West Pacific islands. Returning viremic travelers may ignite autochthonous infections in countries like Italy, which are infested by Aedes albopictus, a suitable vector for ZIKV. The role of clinicians is crucial and includes early diagnosis and timely notification of public health authorities in order to quickly implement adequate focal vector control measurements.

Darunavir-based dual therapy in HIV experienced patients.

BACKGROUND: We assessed the virological response of DRV/r-based dual therapy in drug-experienced patients included in the Italian antiretroviral resistance database (ARCA). MATERIALS AND METHODS: Patients included in the study were treated with DRV/r in association with raltegravir (RAL), etravirine (ETV) or maraviroc (MAR) following treatment failure(s) and with a resistance test and at least one follow-up visit available. Observation was censored at last visit under dual therapy and survival analysis and proportional hazard models were used, taking virological failure (confirmed >50 c/mL HIV-RNA) as the end-point. RESULTS: Of the total 221 patients included, 149 (67.4%) started DRV/r with RAL, 45 (20.4%) with ETV, 27 (12.2%) with MAR. Patients characteristics at the start of dual regimen were as follows: mean number of previous regimens, nine (IQR: 5-13); non-B subtype, 17 (7.7%); median CD4 count, 347 (IQR: 246-544); undetectable viral load, 74 (33.5%). Full DRV/r resistance was detected in one (0.5%, HIV-DB interpretation system), 13 (5.9%, ANRS) and 17 patients (7.7%, Rega). 69 virological failures (31.2%) were observed during follow-up. At survival analysis, the overall proportion of failure was 29.2% at one year and 33.8% at two years. The proportion of failure was lower in patients starting with undetectable versus detectable viral load (13.3% and 25.2% versus 37.4% and 38.8% at one and two years, respectively, p=0.001 for both analyses) and in patients treated with DRV 600 BID versus 800 QD (HR: 0, 56; 95% CI 0.31-0.99; p<0.05). By regimen, patients treated with DRV/r-RAL showed a non-significant lower proportion of failure (27.7% at one year, 32.0% at two years) if compared with DRV/r-MAR (35.9%, 47.1%) and DRV/r-ETV (34.1%, 34.1% at one and two years). In the adjusted proportional model, no significant difference among the three regimens was detected. A significant lower risk of failure was associated with higher overall GSS (HIV-DB HR: 0.53, 95% CI 0.32-0.88, p=0.014; Rega 0.60, 0.40-0.88, p<0.01; ANRS 0.55, 0.34-0.90, p=0.017), while a higher risk of failure was associated with detectable HIV-RNA (3.02, 1.70-5.72, p<0.001). CONCLUSIONS: Among experienced patients, the best candidates to dual-therapy regimens including DRV/r are those with undetectable viral load and higher GSS. The association with RAL is the most commonly used but no clear advantage with respect to ETV or MAR was observed in our dataset, possibly due to the limited sample size.

Interferon lambda 3 rs12979860 polymorphism in patients with haemophilia and HCV infection: a predictor of spontaneous viral clearance and sustained virological response.

Chronic hepatitis C is the main cause of morbidity and mortality in adult haemophilic patients who received non-virally inactivated plasma-derived clotting factor concentrates. Overall, spontaneous viral clearance rate is 10-25% and the only approach that can halt disease progression is hepatitis C virus (HCV) eradication by means of antiviral therapy. In non-haemophilic patients a single nucleotide polymorphism located upstream the gene of interferon lambda 3 (IFNλ3) has been associated with both spontaneous viral clearance and sustained virological response after antiviral treatment. The aim of this study was to assess whether the rs12979860 polymorphism was a predictor of spontaneous viral clearance and of sustained virological response after antiviral therapy in a large cohort of haemophilic patients with HCV infection. The rs12979860 polymorphism, defined as CC genotype or T allele, was tested in a cohort of 342 haemophilic patients and evaluated as predictor of spontaneous clearance or response to antiviral therapy. By multivariate regression analysis the IFNλ3 CC genotype was an independent predictor of spontaneous viral clearance (odds ratio: 3.7, 95% confidence interval: 2.0-6.8). Sustained virological response rates were doubled in patients with the CC genotype than in those with the T allele (78% vs 44%; p<0.001), especially in patients with HCV type 1 (67% vs 32%; p<0.001) and higher sustained response rates were observed in patients with the CC genotype who did not achieve rapid virological response (61% vs 30% in T allele patients; p=0.006).

The effect of leadership on hand hygiene: assessing hand hygiene adherence prior to patient contact in 2 infectious disease units in Tuscany.

We assessed hand hygiene adherence in 2 infectious disease units. In one unit, adherence declined slightly from year 1 (84.2%) to year 4 (71.0%) after a multimodal intervention but remained much higher than before intervention. Adherence dropped in the second unit after a loss of leadership (from 50.7% to 5.7%). Strong leadership presence may improve hand hygiene adherence.

Economic analysis of the first 20 years of universal hepatitis B vaccination program in Italy: an a posteriori evaluation and forecast of future benefits.

Italy was one of the first countries in the world to introduce a routine vaccination program against HBV for newborns and 12-y-old children. From a clinical point of view, such strategy was clearly successful. The objective of our study was to verify whether, at 20 y from its implementation, hepatitis B universal vaccination had positive effects also from an economic point of view. An a posteriori analysis evaluated the impact that the hepatitis B immunization program had up to the present day. The implementation of vaccination brought an extensive reduction of the burden of hepatitis B-related diseases in the Italian population. As a consequence, the past and future savings due to clinical costs avoided are particularly high. We obtained a return on investment nearly equal to 1 from the National Health Service perspective, and a benefit-to-cost ratio slightly less than 1 for the Societal perspective, considering only the first 20 y from the start of the program. In the longer-time horizon, ROI and BCR values were positive (2.78 and 2.46, respectively). The break-even point was already achieved few years ago for the NHS and for the Society, and since then more and more money is progressively saved. The implementation of universal hepatitis B vaccination was very favorable during the first 20 y of adoption, and further benefits will be increasingly evident in the future. The hepatitis B vaccination program in Italy is a clear example of the great impact that universal immunization is able to provide in the medium-long-term when health care authorities are so wise as to invest in prevention.

Self-reported adherence supports patient preference for the single tablet regimen (STR) in the current cART era.

OBJECTIVE: To analyze self-reported adherence to antiretroviral regimens containing ritonavir-boosted protease inhibitors, nonnucleoside reverse transcriptase inhibitors (NNRTI), raltegravir, and maraviroc. METHODS: Overall, 372 consecutive subjects attending a reference center for HIV treatment in Florence, Italy, were enrolled in the study, from December 2010 to January 2012 (mean age 48 years). A self-report questionnaire was filled in. Patients were defined as "nonadherent" if reporting one of the following criteria: <90% of pills taken in the last month, ≥1 missed dose in the last week, spontaneous treatment interruptions reported, or refill problems in the last 3 months. Gender, age, CD4, HIV-RNA, years of therapy, and type of antiretroviral regimen were analyzed with respect to adherence. RESULTS: At the time of the questionnaire, 89.8% of patients had <50 copies/mL HIV-RNA and 14.2% were on their first combined antiretroviral therapy. 57% of patients were prescribed a regimen containing ritonavir boosted protease inhibitors (boosted PI), 41.7% NNRTI, 17.2% raltegravir, and 4.8% maraviroc; 49.5% of the subjects were on bis-in-die regimens, while 50.5% were on OD regimens, with 23.1% of these on the single tablet regimen (STR): tenofovir/emtricitabine/efavirenz. The nonadherence proportion was lower in NNRTI than in boosted-PI treatments (19.4% vs 30.2%), and even lower in STR patients (17.4%). In multivariable logistic regression, patients with the NNRTI regimen (OR: 0.56, 95% CI: 0.34-0.94) and the STR (OR: 0.45, 95% CI: 0.22-0.92) reported lower nonadherence. Efavirenz regimens were also associated with lower nonadherence (OR: 0.42, 95% CI: 0.21-0.83), while atazanavir/ritonavir regimens were associated with higher nonadherence. No other relation to specific antiretroviral drugs was found. A higher CD4 count, lower HIV-RNA, and older age were also found to be associated with lower nonadherence, while a longer time on combined antiretroviral therapy was related to higher nonadherence. CONCLUSION: STR maintains an advantage in improving adherence with respect to other combined antiretroviral therapies, even though new antiretroviral drugs and drug classes have become available in recent years.

Renal complications in HIV disease: between present and future.

The recent introduction of new antiretroviral drugs, characterized by high efficiency and improved safety profiles, has not reduced the incidence of long-term adverse effects, in some cases manifested as selective organ damage. The presence of organ damage in patients receiving antiretroviral treatment is not only the expression of treatment toxicity, but also a complex interaction between individual risk factors, HIV-correlated effects, and antiretroviral drug toxicity. Kidney damage belongs to these adverse events. Renal function abnormalities are present in a large percentage of patients with HIV infection. Moreover, HIV-associated renal disease seems to be associated with progression to AIDS and death. In this review we address the various aspects of the epidemiology of renal damage, the interaction and the convergent effect of HIV and antiretroviral drugs in the onset of kidney injury, the interplay between kidney function and other organ systems, early clinical management, the monitoring of renal function, and a proposal of clinical approach to kidney disease in daily practice. Finally, we discuss future perspectives of renal damage in HIV patients and evaluate the patient's perspective.

Pegylated interferon alfa-2b plus ribavirin in the retreatment of interferon-ribavirin nonresponder patients.

BACKGROUND & AIMS: Inadequate data are available about retreatment of nonresponders to interferon (IFN) and ribavirin. Thus, this study evaluated the efficacy and tolerability of a 48-week therapy with pegylated IFN-alpha-2b plus high-dose ribavirin in patients who have failed to respond to the combination. Treatment up to 48 weeks also in patients who have failed to clear hepatitis C virus (HCV) RNA by week 24 was also evaluated. METHODS: One hundred forty-one patients who previously did not respond to IFN and ribavirin, 86% with genotype 1 or 4 infection, 52% with high viral load (>800.000 IU/mL), 22% with cirrhosis, were retreated with pegylated IFN-alpha-2b 1.5 microg/kg per week and ribavirin 1000-1200 mg/day for 48 weeks and followed up for 24 weeks. RESULTS: By intent-to-treat analysis, 20% of patients achieved a sustained virologic response (SVR). SVR of genotype 1 patients was 19%. Independent predictors of SVR were low gamma-glutamyltransferase levels (OR, 22.9; 95% CI: 6.6-79.6) and low viral load (OR, 3.8; 95% CI: 1.1-12.6). Twelve (23%) out of 51 patients who were HCV RNA positive after 24 weeks of therapy achieved a late virologic response (after week 24) and 5 (10%) of them, all with genotype 1, achieved an SVR. Genotype was not associated with response (P = .2) or with early response (P = .3). CONCLUSIONS: Retreatment with pegylated IFN-alpha-2b and ribavirin of multi-experienced and "difficult to treat" nonresponder patients produced a very promising SVR. Accurate selection of patients, such as those with low viral load and low gamma-glutamyltransferase levels, and prolongation of therapy beyond 24 weeks also in HCV RNA-positive patients may further increase the rate of SVR.

Prolonged treatment interruption in chronic HIV infection: a new strategy?

The introduction of highly active antiretroviral therapy in 1995 dramatically decreased AIDS-related events and deaths rates; however, the enthusiasm among the medical and social community was soon limited by the growing incidence of various side-effects that often greatly limited patients' quality of life. The second problem caused by such a complex treatment consisted of sub-optimal adherence, with a consequent higher risk of the development of drug resistance.