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In December 2019, a novel human-infecting coronavirus, named Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2), was recognised to cause a pneumonia epidemic outbreak with different degrees of severity in Wuhan, Hubei Province in China. Since then, this epidemic has spread worldwide; in Europe, Italy has been involved. Effective preventive and therapeutic strategies are absolutely required to block this serious public health concern. Unfortunately, few studies about SARS-CoV-2 concerning its immunopathogenesis and treatment are available. On the basis of the assumption that the SARS-CoV-2 is genetically related to SARS-CoV (about 82 % of genome homology) and that its characteristics, like the modality of transmission or the type of the immune response it may stimulate, are still poorly known, a literature search was performed to identify the reports assessing these elements in patients with SARS-CoV-induced infection. Therefore, we have analysed: (1) the structure of SARS-CoV-2 and SARS-CoV; (2) the clinical signs and symptoms and pathogenic mechanisms observed during the development of acute respiratory syndrome and the cytokine release syndrome; (3) the modification of the cell microRNome and of the immune response in patients with SARS infection; and (4) the possible role of some fat-soluble compounds (such as vitamins A, D and E) in modulating directly or indirectly the replication ability of SARS-CoV-2 and host immune response.

Randomized, open-label, prospective clinical trial assessing efficacy and safety on hyperlipidemia of a switching from a regimen including one protease inhibitor and one thymidine analogue to atazanavir/ritonavir plus abacavir/lamivudine or tenofovir/emtricitabine. Adult HIV-infected patients on their first antiretroviral therapy (of at least 48-week duration), including one protease inhibitor and zidovudine or stavudine, with stable immunovirologic features, and having diagnosis of persisting hyperlipidemia, were randomized to replace current treatment with atazanavir/ritonavir plus abacavir/lamivudine (arm A) or tenofovir/emtricitabine (arm B), and were followed for 48 weeks. Eighty-nine patients were enrolled: 42 patients were randomized to arm A, and 47 to arm B. At the end of the 48-week follow-up, incidence of virologic failure was comparable in both arms, and associated with a poor drug compliance. Increase in CD4 lymphocyte count was significantly higher in arm A after a 24-week study period (62.5 versus 39.2 x 10(6) cells/L; p < 0.05), while immunologic responses were comparable at the end of 48-week follow-up (91.5 versus 83.6; p > 0.05). A statistically significant reduction (-15.4%) in mean triglyceridaemia versus respective baseline values was reported in both groups (p < 0.05), without statistically significant difference between arm A and B. Similar results were reported for total cholesterol and low-density lipoprotein (LDL) cholesterol levels. Safety and tolerability profiles were comparable in both groups. Switching from a protease inhibitor- and thymidine analogue-based antiretroviral regimen to atazanavir/ritonavir plus abacavir/lamivudine or tenofovir/emtricitabine proved effective in the management of hyperlipidemia, without significant differences in lipid-lowering effect, virologic efficacy, and safety profile between these regimens.

The introduction of novel, fixed nucleoside-nucleotide reverse transcriptase inhibitor (NRTI) combinations (tenofovir-emtricitabine, and abacavir-lamivudine), expanded the spectrum of available formulations and increased patient's adherence. A prospective survey of the open-label use of these two fixed combinations was performed in 158 patients belonging to our single-centre cohort of over 1,000 HIV-infected subjects enrolled in the last 18 months, and followed for at least 12 months. During the last 18 months, 95 consecutive, evaluable patients (60.1%) received for the first time tenofovir-emtricitabine, or abacavir-lamivudine (63 patients, 39.9%), and were followed for at least 12 months. A major role seems to be played by tenofovir-emtricitabine in first-line treatments (preferably among "compact" regimens based on efavirenz), while the proportionally increased abacavir-lamivudine prescription to pre-treated patients is mostly attributable to the different genetic barrier of abacavir (often associated with boosted protease inhibitors, in this last patient group). The present availability to two more fixed NRTI combinations favored by their single pill, once-daily administration encourages randomized, controlled "head to head" studies in both first-line and experienced patients, in order to better exploit and target their therapeutic potential.

The elevated frequency of chronic hepatitis C virus (HCV) infection found among prison inmates, and the availability of improved pharmacological cure for this potentially life-threatening disorder, make investigations conducted in this somewhat neglected area very relevant, since only a few, open-label experiences have been reported till now. In the metropolitan prison of Bologna (Italy), HCV seroprevalence was found to be over 31% in 2003, so that a pilot feasibility study based on treatment with pegylated interferon plus ribavirin was initiated, after careful counseling carried out by a joint commission of health care personnel of the correctional facility and infectious diseases consultants. Thirty-nine patients were enrolled, and despite expected dropouts due to difficulty in maintaining the same level of counseling pressure over time, and the particularly unfavorable climatic conditions during Summer 2003, a sustained virological response was obtained for 8 out of the 21 patients who remained evaluable after the first three month follow-up, although we need to take into account that a high percentage of subjects (67%) were selected for therapy due to their favorable HCV genotypes (types 2 and 3). Our preliminary experience shows that an intrinsically complicated therapy, such as the administration of pegylated interferon plus ribavirin, can attain a relatively high success rate, even in a very unfavorable and uncomfortable context, such as a prison, where only enforced counseling, active participation of institutional health care operators, and patient's willingness to maintain an elevated level of co-operation and adherence, can overcome most structural and relational difficulties.

The unexpected observation of severe pulmonary tuberculosis after a 7-month combined pegylated interferon-ribavirin for chronic hepatitis C, prompted us to search an eventual immunodeficiency (lymphopenia and/or depletion of CD4+ T-lymphocytes. The retrieval of a chest radiograph incidentally performed 11 y before and showing a probable primary tuberculosis, paralleled a negligible clinical history. The enlargement of interferon indications needs careful evaluation for prior (usually missed) tuberculosis, to prevent or avoid its possible reactivation. Latent tuberculosis is increasingly reported because of extended life expectancy, immigration, and recent availability of cure for multiple chronic disorders, which are often borne by primary-secondary immunodeficiency.

Background: A severe, near-fatal liver failure due to a concomitant acute HBV-HCV infection has been controlled and later fully resolved from a clinical and a virological point of view, by a prompt and appropriate antiviral treatment. [ABSTRACT FROM AUTHOR]

The recent introduction of novel, fixed nucleoside-nucleotide reverse transcriptase inhibitor (NRTI) combinations (tenofovir-emtricitabine, and abacavir-lamivudine) expanded the spectrum of available formulations and concurrently increased patients' adherence levels. A prospective survey of the open-label use of these two fixed combinations was performed in 158 patients belonging to our single-center cohort of more than 1,000 HIV-infected subjects enrolled in the last 18 months, and followed for at least 12 months. During the last 18 months, 95 consecutive, evaluable patients (60.1%) received for the first time tenofovir-emtricitabine, or abacavir-lamivudine (63 patients, 39.9%), and were followed for at least 12 months with periodic clinical and laboratory examinations. Among the 53 evaluable patients who were naïve to all antiretrovirals, tenofovir-emtricitabine has been given to 42 subjects (79.2%), mostly associated with efavirenz (26 cases), or different boosted protease inhibitors (16 subjects), whereas abacavir-lamivudine was administered to 11 patients (in 10 cases of 11, together with boosted protease inhibitors). In the remaining 105 patients, tenofovir-emtricitabine or abacavir-lamivudine therapy represented a switch from a prior combination antiretroviral regimen, and was predominantly associated with boosted protease inhibitors (61 patients), versus efavirenz or nevirapine (26 cases), or other drug combinations containing protease inhibitors (the remaining 18 patients). Among the 105 pretreated patients, the prescription of tenofovir-emtricitabine (53 patients) was as frequent as that of abacavir-lamivudine (52 cases), and the therapeutic change was primarily prompted by toxicity or poor tolerability (59 patients), followed by therapeutic failure and viral resistance (46 cases as a whole), and always encompassed a regimen simplification also. Both fixed combinations were well tolerated, and an adherence rate more than 90% was estimated among evaluable patients. From a tolerability point of view, the emtricitabine-tenofovir association was never withdrawn due to untoward events, while only two cases of early abacavir-lamivudine suspension occurred, due to a probable abacavir hypersensitivity reaction. From our preliminary experience, a major role seems to be played by tenofovir-emtricitabine in first-line treatments (preferably among “compact” regimens based on efavirenz), while the proportionally increased abacavir-lamivudine prescription to pretreated patients is mostly attributable to the different genetic barrier of abacavir (which was often associated with boosted protease inhibitors, in this last patient group). The present availability of two more fixed NRTI combinations favored by their single pill, once-daily administration strongly encourages randomized, controlled “head to head” studies in both first-line and experienced patents, in order to better exploit and target their therapeutic potential, and their most effective associations. [ABSTRACT FROM AUTHOR]

The article report that the guidelines for antiretroviral therapy state that nevirapine pharmacokinetics are not significantly affected by pregnancy, although some pregnant HIV-positive women face an increased risk of fatal liver toxicity, often associated with rash. Although the hepatotoxicity of nevirapine is greater than that of efavirenz, the potential for pregnancy and CD4 cell count-related increased hepatotoxicity is uncertain.

Two very rare case reports of bladder transitional cell carcinoma associated with HIV infection in patients treated with combined antiretroviral therapy are described, and discussed on the ground of the most relevant and updated literature resources. Only 13 cases of vesical carcinoma have been reported to date in the setting of HIV infection, but only 3 anecdotal single reports (the last in the y 2001) described clinical, therapeutic, and outcome issues of this rare disease association in some detail. In our patients, micro- or macro- haematuria was the clue for in-depth diagnosis and prompt treatment, which was limited to multiple local interventions in 1 case, but finally required a radical cystectomy in the second patient. No relationship was found with the very favourable underlying HIV-related virological and immunological status, and the present 8–12-month follow-up did not show disease relapses. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to evaluate the temporal trend of deaths in a cohort of intravenous (IV) drug users (IVDU) followed in a city in Northern Italy (Bologna), and to assess its relationship with HIV infection and AIDS, and availability of potent antiretroviral therapy. Methods: A total of 1214 IVDUs (mainly heroin addicts). 916 males and 298 females, attending an outpatient service for treatment and prevention of substance abuse between 1977 and November 1996, were enrolled into our observational cohort. Their vital status was ascertained up to December 31, 2002. Results: The large majority of enrolled subjects were born in the Bologna metropolitan area and surroundings; no extra-European immigrants were pres present. During the observation period. 271 IVDUs (22.3%) died, 211 males (23.0%), and 60 females (20.1 %). No death was recorded before 1984. Main death causes were as follows: AIDS (52.8% of deaths), heroin overdose (22.1%), street accidents (7.4%), decompensated liver cirrhosis (6.3%), and suicide (2.9%). The highest absolute number of deaths was observed between years 1991 and 1996. Crude mortality rate caused by AIDS was 10.0 per 1000 for males and 13.2 per 1000 for females; the rate of death due to other causes proved 11.1/1000 among males and 5.2/1000 among females. Conclusion: In most recent years, a sharp decrease in the number of AIDS related deaths, attributable to the increased use of potent antiretroviral regimens, was recorded among IVDUs, although overall mortality rate remained appreciable. [ABSTRACT FROM AUTHOR]

Objective and methods: The aim of our study was to analyse retrospectively the nature and frequency of antiretroviral prescriptions for 990 HIV-infected patients followed at our outpatient centre in Bologna, Italy, from January 2003 to March 2004. The main focus of the study was to identify the most commonly prescribed combinations and their related expenses, in order to identify the most competitive treatment regimens with regard to costs. Prescriptions were given directly to patients at monthly intervals, and drug treatment adherence data was stored in an electronic database. Antiretroviral regimens administered for the longest period to each patient during the 15 months of the study were selected for the study. All patients treated for <9 consecutive months and/or with treatment adherence levels <90% were excluded. Physicians assessed antiretroviral therapy at least quarterly according to efficacy and safety criteria, but not in terms of pharmacoeconomic considerations. Direct pharmacy expenses were obtained for the 24 most commonly used therapeutic regimens, covering 80.1% of patients. Results: The zidovudine-lamivudine-efavirenz combination proved to be the most prescribed combination (7.3%), followed by zidovudine-lamivudine- nevirapine (7.1%), lamivudine-stavudine (6.2%), zidovudine-lamivudine- lopinavir-ritonavir (5.2%), didanosine-stavudine-lopinavir-ritonavir (4.8%), and lamivudine-stavudine-nevirapine (4.7%). Anti-HIV combinations varied from a minimum yearly cost of €3895.6 for lamivudine-stavudine to €9422.8 for the zidovudine-lamivudine-lopinavir-ritonavir combination (+241.9%) [year of costing 2003]. There was a significant difference between the two first-line regimens for antiretroviral-naive subjects, with lopinavir-ritonavir-based combinations costing more than €9000 per patient/year compared with efavirenz-containing combinations, which were 28% less expensive. Mean daily costs varied substantially, from a minimum of €10.7 per day for lamivudine-stavudine to a maximum of €25.8 per day (+241.1%) for zidovudine-lamivudine-lopinavir-ritonavir. Regimens based on non-nucleoside reverse transcriptase inhibitors (NNRTIs) were less costly than most of those including protease inhibitors (PIs). The increased expense of each combination was compared with the cheapest therapeutic selection (lamivudine-stavudine), and costs of all triple combinations were also compared. Regimens based on NNRTIs accounted for 29.3% of our cohort (nevirapine-containing therapies 15.1%, and efavirenz-based ones 14.2%), while PIs were used in the majority of cases (37.3%), with lopinavir-ritonavir as the leading combination (13.6% of patients), followed by nelfinavir (9.9%) and indinavir (9.2%). When drug-related costs were examined, dual nucleoside analogues showed the lowest expense (€10.7–€11.6 per day), while triple nucleoside/nucleotide analogue combinations cost nearly twice as much (€18.5–€20.4 per day). Among the NNRTIs, there were comparable costs for nevirapine-based combinations (€18.3–€18.7 per day), while efavirenz-including regimens were 10% more costly (€19.2–€20.l per day). A very broad range of combinations and related costs were found with PIs, but apart from indinavir and saquinavir combinations (€15.7–€21.7 per day), all other regimens had a higher daily cost (from €22.0 per day for ritonavir-based regimens to €23.4–€24.3 per day for nelfinavir combinations, and up to €24.9–€25.8 per day with lopinavir-ritonavir). When considering nelfinavir- and lopinavir-containing combinations, the difference compared with NNRTI-based regimens varied from 41% when nevirapine- and lopinavir-ritonavir were compared, to 11.6% when efavirenz and nelfinavir were compared. Conclusions: Investigations that link prescribing patterns and related costs in the setting of HIV disease therapy are needed to improve patient management and help with the planning of healthcare resource allocation. [ABSTRACT FROM AUTHOR]

Compares the effectiveness and tolerability of the nonnucleoside reverse transcriptase inhibitors, afavirenz versus nevirapine in all possible indications of current clinical practice. Baseline assessment; Follow-up of efficacy parameters; Tolerability evaluation; Efficacy parameters.

An extraordinarily rare case report of mixed fat redistribution syndrome associated with osteopenia but not with relevant metabolic abnormalities is documented in a prepubertal child with congenital HIV infection treated with antiretroviral therapy since the age of six months, up to the present age of 12 years and two months. The possible relationship with prior and present antiretroviral treatment, and with the most recent literature evidences published in both adults and children with HIV disease are discussed, in order to focus these emerging adverse effects of long-term antiretroviral therapy in the paediatric population, and stimulate further investigation in this field. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented about different combinations of antiretroviral agents.

Presents a letter to the editor discussing a cross-sectional evaluation assessing the metabolic safety profile of the two available nonnucleoside reverse transcriptase inhibitors (NNRTIs), efavirenz and nevirapine that allowed the identification of 1018 HIV-infected patients treated with highly active antiretroviral therapy (HAART) within twelve months.

A possible association between carpal tunnel syndrome and HIV infection has been suggested only once until now. Two patients with HIV infection are described who presented confirmed carpal tunnel syndrome while on prolonged protease inhibitor-containing highly active antiretroviral therapy (HAART). Their disease course and long-term outcome after medical and/or surgical interventions is presented and discussed according to available evidence from the literature. In our patients, carpal tunnel syndrome occurred in apparent absence of all presumed risk factors of this disease and metabolic abnormalities potentially related to HIV protease inhibitor administration. [ABSTRACT FROM AUTHOR]

A 16-year-old girl with vertical HIV disease treated since birth suffered from six different AIDS-defining disorders until now. Even during the highly active antiretroviral therapy, multiple AIDS-related opportunistic infections may complicate the course of long-term congenital HIV disease, showing a strict relationship with immunological deterioration, which occurs shortly after virologic failure, due to an extensive genotypic resistance to all available antiretroviral compounds. [ABSTRACT FROM AUTHOR]