Search

Previous studies reported that the hepatitis C virus (HCV) could help disseminate the hepatitis D virus (HDV) in vivo through hepatitis B virus (HBV)-unrelated ways, but with essentially inconclusive results. To try to shed light on this still-debated topic, 146 anti-HCV-positive subjects (of whom 91 HCV/HIV co-infected, and 43 with prior HCV eradication) were screened for anti-HDV antibodies (anti-HD), after careful selection for negativity to any serologic or virologic marker of current or past HBV infection. One single HCV/HIV co-infected patient (0.7%) tested highly positive for anti-HD, but with no positive HDV-RNA. Her husband, in turn, was a HCV/HIV co-infected subject with a previous contact with HBV. While conducting a thorough review of the relevant literature, the authors attempted to exhaustively describe the medical history of both the anti-HD-positive patient and her partner, believing it to be the key to dissecting the possible complex mechanisms of HDV transmission from one subject to another, and speculating that in the present case, it may have been HCV itself that behaved as an HDV helper virus. In conclusion, this preliminary research, while needing further validation in large prospective studies, provided some further evidence of a role of HCV in HDV dissemination in humans.

Cardiovascular disease (CVD) is common in people with HIV (PWH), and has great impact in terms of morbidity and mortality. Several intertwined mechanisms are believed to play a role in determining the increased risk of CVD, including the effect of certain antiretrovirals; among these, the role of integrase strand-transfer inhibitors (INSTIs) is yet to be fully elucidated. We conducted a multicenter, observational study comprising 4984 PWH evaluating the antiretroviral therapy (ART)-related nature of CVD in real life settings, both in naïve vs. treatment-experienced people. A comparison was conducted between INSTIs vs. either protease inhibitors (PIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs) considering demographic, baseline clinical characteristics, incidence of CVD in both 2-year and complete follow-up periods. Among 2357 PWH exposed to INSTIs, 24 people experienced CVD; the corresponding figure was 12 cases out of 2599 PWH exposed to other ART classes. At univariate and multivariate analysis, a tendency towards an increased risk of CVD was observed in the 2-year follow-up period in PWH exposed to INSTIs in the absence, however, of statistical significance. These findings leave open the hypothesis that INSTIs may play a role, albeit minimal, in determining an increased risk of CVD in PWH.

Introduction: Integrase strand transfer inhibitors (INSTI) are one of the most prescribed drug classes for the treatment of HIV infection worldwide. Emtricitabine/Tenofovir Alafenamide/ Bictegravir (FTC/TAF/BIC) has been evaluated in randomized clinical trials; few studies have verified tolerability and safety in clinical practice. Our aim was to investigate the metabolic and hepatic safety in a real-life setting of FTC/TAF/BIC., Materials and Methods: Consecutive people living with HIV infection (PLWH) enrolled in the SCOLTA project, switching to or initiating their first antiretroviral treatment with FTC/TAF/BIC were included. PLWH with HBV co-infection were excluded. Metabolic and hepatic variables were collected at T0 and T1, were defined as baseline and 6-month follow-up respectively, and their modifications were analysed using the paired t-test and the analysis of variance., Results: Five hundred and thirty-nine PLWH with at least one follow-up visit were included in the analysis. Mean age was 48 years (±12.1), 74% were male, 16.1% were naïve to antiretrovirals (ART). At T1, ART-experienced PLWH showed a significant reduction of total cholesterol (TC) and triglycerides, and a slight increase in blood glucose (BG) and ALT. On the contrary, in ART-naïve PLWH blood lipids significantly increased, although with an unaffected TC/high density lipoprotein (HDL)-c ratio, while alanine aminotransferase (ALT) decreased significantly, mainly in those with altered baseline level. The treatment interruptions were 45 (8.4%) over the whole observation period, 13 (2.4%) due to AEs. The most frequent AEs were related to the central nervous system (6 events of depression, insomnia, headache, agitation) and 3 PLWH discontinued the regimen because of grade 1-2 weight gain., Conclusions: In ART-experienced PLWH switching to FTC/TAF/BIC a significant improvement of lipid profile occurred but with significant BG and ALT variation without clinical relevance. In ART-naïve PLWH, blood lipids increased even though lipid profile did not worsen, and a trend towards normalization of liver enzymes was suggested. FTC/TAF/BIC is well tolerated in the real life setting., Competing Interests: “The following authors served as consultant or advisory board and/or received speaker’s fees and/or received research grants for their institutions, outside the present work: PM and GFP from Gilead Science, ViiV Healthcare, Janssen and Merck Sharp & Dohme, PB from Gilead Science, ViiV Healthcare, Janssen, Merck Sharp & Dohme and Pfizer. ADB from Gilead Science, ViiV Healthcare and Janssen. RB from Gilead Science, ViiV Healthcare, and Merck Sharp & Dohme. AC from Gilead Science, Janssen, Merck Sharp & Dohme; NS from ViiV Healthcare, Janssen and Gilead Sciences; LT from ViiV Healthcare and Gilead Science; GVDS from ViiV Healthcare. All remaining authors have no potential conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.”, (Copyright: © 2023 Squillace et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Doravirine (DOR) is a newly approved non-nucleoside reverse transcriptase inhibitor (NNRTI). We aimed to investigate, in a real-life setting, how switching to a DOR-based regimen rather than a rilpivirine (RPV)-based regimen impacted metabolic and hepatic safety. The analysis included 551 antiretroviral treatment (ART)-experienced people living with HIV (PLWH), starting RPV-based or DOR-based regimens with viral load < 200 copies/mL, baseline (T0), and at least one control visit (6-month visit, T1). We enrolled 295 PLWH in the RPV and 256 in the DOR cohort. At T1, total cholesterol (TC), low-density lipoprotein-C (LDL-C), and triglycerides significantly decreased in both DOR and RPV cohorts, while high-density lipoprotein-C (HDL-C) only decreased in RPV-treated people. Consistently, the TC/HDL-C ratio declined more markedly in the DOR (-0.36, p < 0.0001) than in the RPV cohort (-0.08, p = 0.25) (comparison p = 0.39). Similar trends were observed when excluding the PLWH on lipid-lowering treatment from the analysis. People with normal alanine aminotransferase (ALT) levels showed a slight ALT increase in both cohorts, and those with baseline ALT > 40 IU/L experienced a significant decline (-14 IU/L, p = 0.008) only in the DOR cohort. Lipid profile improved in both cohorts, and there was a significant reduction in ALT in PLWH with higher-than-normal baseline levels on DOR-based ART.

Background: Doravirine (DOR) is a newly approved antiretroviral belonging to the class of non-nucleoside reverse transcriptase inhibitors (NNRTI), well tolerated and leading to an improved lipid profile in antiretroviral experienced people living with HIV (PLWH). We aimed at evaluating if the lipid-lowering effect is linked to the drug class, using real-life data from the SCOLTA cohort., Methods: We compared the lipid profile modifications in experienced PLWH switching to a DOR-based regimen from rilpivirine or another NNRTI-based regimen or from an integrase strand transferase (INSTI)-based regimen. T0 and T1 were defined as the baseline and 6-month follow-up respectively. Data were collected at baseline and prospectively every six months and changes from baseline were compared using a multivariable linear model., Results: In 107 PLWH, enrolled in the SCOLTA DOR cohort, with undetectable HIV-RNA at baseline, 32.7% switched from RPV-based regimens (DOR1), 29.9% from other NNRTI-including regimens (DOR2) and 37.4% switched from INSTI-including regimens (DOR3). At T1, TC significantly decreased in DOR2 (-15 mg/dL) and DOR3 (-23 mg/dL), and significantly more in DOR3 than in DOR1 (-6 mg/dL) (p = 0.016). HDL-C declined in DOR2 (-2 mg/dL) whereas it increased in DOR1 (+ 3 mg/dL) (p = 0.042) and remained stable in DOR3. LDL-C significantly decreased from baseline in DOR2 (-12 mg/dL) and DOR3 (-22 mg/dL) and was different between DOR1 (-8 mg/dL) and DOR3 (p = 0.022). TC/HDL ratio showed a significant decline in the DOR3 group (-0.45), although similar to DOR1 (-0.23, p = 0.315) and DOR2 (-0.19, p = 0.254). Triglycerides did not noticeably change. ALT significantly decreased in PLWH with a baseline level > 40 UI/mL., Conclusions: PLWH on doravirine treatment showed different trends in blood lipids according to their previous regimen. In PLWH switching from RPV, minimal modifications were seen, whereas in those switching from other NNRTIs and from INSTI-including regimens, we observed an overall improvement in lipid profile, seemingly independent of the "statin effect" of TDF., (© 2023. The Author(s).)

Intravenous drug use is a predisposing condition for infective endocarditis (IE). We report the clinical features of IE, taken from the Italian Registry of IE, in people who inject drugs (PWIDs). The registry prospectively collected epidemiological, clinical, in-hospital, and follow-up data on patients with IE from 17 Italian centers. A total of 677 patients were enrolled, and 61 (9%) were intravenous drug users (IDUs). Most PWIDs were male (78.6%), and aged between 41 and 50 years old (50%). The most frequent comorbidities were HIV (34.4%) and chronic liver disease (32%). Predisposing factors for IE were present in 6.5% of the patients, and 10% had minor valvular abnormalities. IE had occurred previously in 16.4% of the patients, and 50% of them had undergone heart surgery. Overall mortality was 9.8% in IDUs and 20% in patients with recurrent IE. IE in PWIDs mostly affected the native valves (90%). The echocardiographic diagnosis of IE was based on the detection of vegetation in 91.82% of cases. Staphylococcus aureus was the main microorganism isolated (70%) from blood cultures. Thirty patients (49%) underwent heart surgery: thirteen had aortic valves, eleven had mitral valves, and six had tricuspid valve interventions. IE in PWIDs was relatively common, and patients with native valve right-sided IE had a better prognosis, with a low rate of surgical interventions.

Hepatitis A (HA) is caused by a hepatovirus from the family Picornaviridae (Hepatitis A Virus, HAV). Transmission occurs mainly by the orofaecal route through food or water contaminated by faeces. Sexual transmission has also been reported among men who have sex with men (MSM). From February to May 2017, 14 patients with HA were hospitalized at the University Hospital "Maggiore della Carità", Novara (Eastern Piedmont), Italy. One patient was two years old and was therefore admitted to the Paediatric Unit, the remaining 13 to the Infectious Disease Unit. Two of the adults were female and the rest (11) were male. The male patients were MSM, and contracted the infection sexually; three of them were known to be HIV positive, while two had a new diagnosis of syphilis infection. Women contracted the infection from contaminated food.

This report describes a case of Sphingobacterium hotanense bacteraemia in a patient scratched by a rooster on the right arm. Diagnostic, clinical and therapeutic features are discussed. To the best of our knowledge, this is the first case of Sphingobacterium hotanense bacteremia reported in the medical literature.

Malaria, the most common parasitic disease in the world, is transmitted to the human host by mosquitoes of the genus Anopheles. The transmission of malaria requires the interaction between the host, the vector and the parasite.The four species of parasites responsible for human malaria are Plasmodium falciparum, Plasmodium ovale, Plasmodium malariae and Plasmodium vivax. Occasionally humans can be infected by several simian species, like Plasmodium knowlesi, recognised as a major cause of human malaria in South-East Asia since 2004. While P. falciparum is responsible for most malaria cases, about 8% of estimated cases globally are caused by P. vivax. The different Plasmodia are not uniformly distributed although there are areas of species overlap. The life cycle of all species of human malaria parasites is characterised by an exogenous sexual phase in which multiplication occurs in several species of Anopheles mosquitoes, and an endogenous asexual phase in the vertebrate host. The time span required for mature oocyst development in the salivary glands is quite variable (7-30 days), characteristic of each species and influenced by ambient temperature. The vector Anopheles includes 465 formally recognised species. Approximately 70 of these species have the capacity to transmit Plasmodium spp. to humans and 41 are considered as dominant vector capable of transmitting malaria. The intensity of transmission is dependent on the vectorial capacity and competence of local mosquitoes. An efficient system for malaria transmission needs strong interaction between humans, the ecosystem and infected vectors. Global warming induced by human activities has increased the risk of vector-borne diseases such as malaria. Recent decades have witnessed changes in the ecosystem and climate without precedent in human history although the emphasis in the role of temperature on the epidemiology of malaria has given way to predisposing conditions such as ecosystem changes, political instability and health policies that have reduced the funds for vector control, combined with the presence of migratory flows from endemic countries.

Central Nervous System (CNS) infections related to external ventricular derivation are a major complication of patients undergoing neurosurgical procedures. Antimicrobial treatment of CNS infections should be based not only on the susceptibility of the isolated microorganism, but also on the treatment's pharmacokinetic properties demonstrating the passage of the molecule through the blood-brain barrier. When CNS infections are caused by multi-drug resistant Gram-negative bacteria, intrathecal colistin is considered an effective and safe option. We review the literature of intrathecal/intraventricular use of colistin, comprehensive of both pharmacokinetic data and clinical experiences.

The increase in temperatures recorded since the mid-nineteenth century is unprecedented in the history of mankind. The consequences of climate changes are numerous and can affect human health through direct (extreme events, natural disasters) or indirect (alteration of the ecosystem) mechanisms. Climate changes have repercussions on ecosystems, agriculture, social conditions, migration, conflicts and the transmission mode of infectious diseases. Vector-borne diseases are infections transmitted by the bite of infected arthropods such as mosquitoes, ticks, triatomines, sand flies and flies. Epidemiological cornerstones of vector-borne diseases are: the ecology and behaviour of the host, the ecology and behaviour of the vector, and the population's degree of immunity. Mosquito vectors related to human diseases mainly belong to the genus Culex, Aedes and Mansonia. Climate changes in Europe have increased the spread of new vectors, such as Aedes albopictus, and in some situations have made it possible to sustain the autochthonous transmission of some diseases (outbreak of Chukungunya virus in northern Italy in 2007, cases of dengue in the South of France and in Croatia). Despite the eradication of malaria from Europe, anopheline carriers are still present, and they may allow the transmission of the disease if the climatic conditions favour the development of the vectors and their contacts with plasmodium carriers. The tick Ixodes ricinus is a vector whose expansion has been documented both in latitude and in altitude in relation to the temperature increase; at the same time the related main viral and bacterial infections have increased. In northern Italy and Germany, the appearance of Leishmaniasis has been associated to climatic conditions that favour the development of the vector Phlebotomus papatasi and the maturation of the parasite within the vector, although the increase of cases of visceral leishmaniasis is also related to host immune factors, particularly immunodepression caused by the human immunodeficiency virus (HIV). Despite the importance of global warming in facilitating the transmission of certain infectious diseases, due consideration must be taken of the role played by other variables, such as the increase in international travel, migration and trade, with the risk of importing parasites and vectors with the goods. In addition, the control of certain infections was possible in the past through improvements in socio-economic conditions of affected populations. However, the reduction in resources allocated to health care has recently led to the re-emergence of diseases that were considered eradicated.

In the past decade health care expenses have increased by 50% in Italy, a country whose population mostly consists of people aged over 50 years old, the main users of health care services. Pharmaceutical expenditure is the main issue: monoclonal antibodies, biological immunosuppressants, antitumorals and antiretrovirals are the most expensive drugs. The cost of HIV/AIDS has remained constant during the last four years. Despite the increase in pharmaceutical costs, which made the infection chronic, hospitalization costs have been reduced. With sustainable economic development as a chiefly long-term target, a clinical governance system is nonetheless needed which also takes account of the adherence to antiretroviral therapy: thus poor adherence leads to a reduction in efficacy and at the same time an increase in welfare and community costs. Recently in SSvD "Prevention and cure of HIV infection and related syndromes" of "Maggiore della Carità" University Hospital, Novara, adherence to antiretroviral therapy in 100 consecutive patients was evaluated. The results show that patients with high adherence to the treatment prescribed have a less expensive drug combination. Moreover, with better infection control and a higher immune recovery, they have less impact on social and health care costs.

We describe the case of a young man who suffered from relapsing infections of a cranial prosthesis implanted in 1982 after a serious accident. The presence of a bacterial infection was diagnosed by microbiological assays performed on purulent drainage from the surgical wound, removed prosthetic material and bone biopsies obtained intraoperatively. The first prosthesis infection was sustained by two nosocomial pathogens, Enterobacter cloacae and methicillin-resistant Staphylococcus aureus (MRSA); it was treated for eight weeks with parenteral antibiotic therapy, including teicoplanin and piperacillin/tazobactam, in association with surgical debridement and prosthesis removal. The following relapse, sustained by Enterobacter cloacae, was treated with a prolonged course of parenteral antibiotic therapy and prosthesis substitution. A third infection was diagnosed two months after the last cranioplasty: cultures of purulent drainage grew MRSA and Staphylococcus gallinarum. In addition to radical debridement, oral antibiotic treatment including linezolid was introduced. Antibiotic therapy was stopped after 10 weeks; at a follow-up visit performed after three years no signs or symptoms of relapse were evident. This case shows the difficulty in eradicating prosthesis infections, and demonstrates the central role of radical surgical debridement and the need of appropriate antibiotic treatment in dosing and duration.

This study reports the results of a one-day point prevalence study of infections performed in 2001 (SPIR01) and 2002 (SPIR02) in a Regional network of ICUs in Piedmont, Italy. The study aims were to illustrate the overall proportion of infected patients and the rate of ICU-acquired infections. Mortality rate was evaluated three weeks after the study days. Resistance pattern of Staphylococcus aureus, coagulase negative Staphylococci and Pseudomonas aeruginosa were recorded. The primary end-point of the study was to document the prevalence and associated risk factors of the ICU-acquired infections, and the impact of infections on mortality. The prevalence of ICU-acquired infection was 30% in SPIR01, and 38.3% in SPIR02. The rate of methicillin-resistance was high among isolates of Staphylococcus aureus and coagulase-negative Staphylococci. The prevalence of ICU-acquired infections was lower than that reported in the EPIC study. In our experience, this Regional survey stimulated further research and collaboration to improve the prophylaxis, diagnosis and treatment of ICU-acquired infections.

Injection drug use is the leading risk factor for infection with hepatitis C virus, and interferon (IFN) treatment in this context is associated with a poor rate of adherence. In this article, we review our experience with injection drug users with acute hepatitis C who are treated with pegylated IFN- alpha -2b for 12 weeks. Acute hepatitis C was diagnosed according to standardized criteria, and patients were treated with a median dosage of IFN- alpha -2b of 1.33 microg/kg per week. A sustained virological response was achieved in 17 (74%) of 23 patients. A sustained virological response was achieved in 14 (87%) of 16 patients treated with a dosage of >or=1.33 microg/kg per week and in 3 (43%) of 7 patients treated with a lower dosage. Sustained virological response was significantly associated only with a pegylated IFN- alpha -2b dosage >or=1.33 microg/kg per week (P=.022). A 12-week regimen of pegylated IFN to treat injection drug users with hepatitis C has a compliance that is much higher than that reported with a 24-week regimen. Adverse effects are minimal if patients are carefully selected.

Fifty-five patients placed on tipranavir/ritonavir 500/200 mg twice a day (27 with enfuvirtide and 28 without) underwent tipranavir and ritonavir plasma concentration measurements by high-pressure liquid chromatography. Markedly higher tipranavir and ritonavir trough concentrations were observed in enfuvirtide recipients. The modelling of sparse plasma samples using a first order absorption and elimination monocompartmental model without time lag predicted higher tipranavir elimination half-life and volume of distribution in enfuvirtide takers. This unexpected drug-drug interaction warrants further investigation.

Options for antiretroviral therapy in patients infected with HIV continue to expand as new drugs are integrated into treatment regimens. Nucleoside/nucleotide reverse transcriptase inhibitors (Nt/NRTIs) remain the backbone of highly active antiretroviral therapy (HAART). Although this is the oldest class of antiretrovirals, pharmacokinetic and pharmacodynamic properties have been less studied as compare to protease inhibotors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). The aim of this article is to review the current status of clinical pharmacology onf Nt/NRTIs, highlighting the issues with clinical interest. Therefore, implications of intracellular pharmacokinetics on dosing schedule, potential for drug-drug interaction and pharmacodynamics is discussed.