Epidemiological and molecular characterization of HBV and HCV infections in HIV-1-infected inmate population in Italy: a 2017-2019 multicenter cross-sectional study.

HBV/HCV co-infection is common in HIV-1-infected prisoners. To investigate the characteristics of HIV co-infections, and to evaluate the molecular heterogeneity of HIV, HBV and HCV in prisoners, we carried-out a multicenter cross-sectional study, including 65 HIV-1-infected inmates enrolled in 5 Italian detention centers during the period 2017-2019. HIV-1 subtyping showed that 77.1% of inmates were infected with B subtype and 22.9% with non-B subtypes. Italian nationals were all infected with subtype B (93.1%), except two individuals, one infected with the recombinant form CRF72_BF1, and the other with the HIV-1 sub-subtype A6, both previously not identified in inmates of Italian nationality. Non-Italian nationals were infected with subtype B (52.6%), CRFs (36.8%) and sub-subtypes A1 and A3 (5.2%). HIV variants carrying resistance mutations to NRTI, NNRTI, PI and InSTI were found in 7 inmates, 4 of which were never exposed to the relevant classes of drugs associated with these mutations. HBV and/or HCV co-infections markers were found in 49/65 (75.4%) inmates, while 27/65 (41.5%) showed markers of both HBV and HCV coinfection. Further, Italian nationals showed a significant higher presence of HCV markers as compared to non-Italian nationals (p = 0.0001). Finally, HCV phylogenetic analysis performed in 18 inmates revealed the presence of HCV subtypes 1a, 3a, 4d (66.6%, 16.7% and 16.7%, respectively). Our data suggest the need to monitor HIV, HBV and HCV infections in prisons in order to prevent spreading of these viruses both in jails and in the general population, and to implement effective public health programs that limit the circulation of different genetic forms as well as of viral variants with mutations conferring resistance to treatment.

The current and future off-label uses of dalbavancin: a narrative review.

Dalbavancin is a novel long-acting semi-synthetic lipoglycopeptide. It is licensed for acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci. Many studies on dalbavancin alternative use in clinical practice have been published recently, including osteomyelitis, prosthetic joint infections (PJIs), and infective endocarditis (IE). Thus, we conducted a narrative review on dalbavancin efficacy in difficult-to-treat infections, such as osteomyelitis, PJIs, and IE. We performed a comprehensive literature search through electronic databases (PubMed-MEDLINE) and search engines (Google Scholar). We included peer-reviewed publications (articles and reviews), and grey literature on dalbavancin use in osteomyelitis, PJIs, and IE. No time or language restrictions have been established. Despite the great interest in clinical practice, only observational studies and case series on the use of dalbavancin in infections other than ABSSSI are available. The reported success rate was extremely variable between studies, ranging from 44% to 100%. A low success rate has been reported for osteomyelitis and joint infections, while in endocarditis, the success rate was higher than 70% in all studies. However, there is no literature agreement about the correct regimen of dalbavancin for this type of infection heretofore. Dalbavancin showed great efficacy and a good safety profile, not only in patients with ABSSSI but also in those with osteomyelitis, PJIs, and endocarditis. Further randomized clinical trials are needed to assess the optimal dosing schedule depending on the site of infection. Implementing therapeutic drug monitoring for dalbavancin may represent the future step to achieving optimal pharmacokinetic/pharmacodynamic target attainment.

Infections in lung transplanted patients: A review.

Lung transplantation can improve the survival of patients with severe chronic pulmonary disorders. However, the short- and long-term risk of infections can increase morbidity and mortality rates. A non-systematic review was performed to provide the most updated information on pathogen, host, and environment-related factors associated with the occurrence of bacterial, fungal, and viral infections as well as the most appropriate therapeutic options. Bacterial infections account for about 50% of all infectious diseases in lung transplanted patients, while viruses represent the second cause of infection accounting for one third of all infections. Almost 10% of patients develop invasive fungal infections during the first year after lung transplant. Pre-transplantation comorbidities, disruption of physical barriers during the surgery, and exposure to nosocomial pathogens during the hospital stay are directly associated with the occurrence of life-threatening infections. Empiric antimicrobial treatment after the assessment of individual risk factors, local epidemiology of drug-resistant pathogens and possible drug-drug interactions can improve the clinical outcomes.

Is oral antibiotic therapy as effective as intravenous treatment in bacterial osteomyelitis? A real-life experience.

OBJECTIVE: Osteomyelitis is a relatively understudied disease with no standardized and evidence-based approach to treatment. We aimed to evaluate a cohort of patients with osteomyelitis, comparing the outcomes between intravenous (IV) and oral treatment. PATIENTS AND METHODS: We performed an observational retrospective study on osteomyelitis cases in adult patients seen for care between 2017 and 2019. We collected information on patient characteristics, microbiological etiology, infection treatment, and outcome. In addition, we divided osteomyelitis cases by antibiotic regimens [oral (OTG) vs. intravenous±oral (ITG)] and therapy durations to evaluate outcomes differences. RESULTS: A total of 235 episodes of osteomyelitis were evaluated, with a higher prevalence in male gender. Staphylococci, especially S. aureus, were the most common strains. Out of the 235 evaluated episodes, we selected 142 cases. Of these, 75 were treated with OTG and 67 with ITG. Gram-positive bacteria were the most frequent aetiological agents, with 81 isolates (61.8%). Full recovery was observed in 79 (55.6%) cases; of these, 36 (53.7%) were in the ITG and 43 (57.3%) in the OTG (p = 0.666). At the logistic regression, a polymicrobial infection [OR 4.16 (95%CI 1.28-13.4), p = 0.017] and a less than six weeks treatment duration [OR 4.24 (95%CI 1.38-5.43) p = 0.004] were significantly associated with a higher risk of treatment failure. CONCLUSIONS: Our study suggests that oral treatment efficacy is comparable to ITG therapy for osteomyelitis, confirming the most recent evidence suggesting that oral therapy is non-inferior to intravenous therapy to treat osteomyelitis.

Systemic inflammatory markers and psychophysical olfactory scores in coronavirus disease 2019 patients: is there any correlation?

OBJECTIVE: To analyse the correlations between olfactory psychophysical scores and the serum levels of D-dimer, C-reactive protein, ferritin, lactate dehydrogenase, procalcitonin and neutrophil-to-lymphocyte ratio in coronavirus disease 2019 patients. METHODS: Patients underwent psychophysical olfactory assessment with the Connecticut Chemosensory Clinical Research Center test, and determination of blood serum levels of the inflammatory markers D-dimer, C-reactive protein, ferritin, lactate dehydrogenase, procalcitonin and neutrophil-to-lymphocyte ratio within 10 days of the clinical onset of coronavirus disease 2019 and 60 days after. RESULTS: Seventy-seven patients were included in this study. D-dimer, procalcitonin, ferritin and neutrophil-to-lymphocyte ratio correlated significantly with severe coronavirus disease 2019. No significant correlations were found between baseline and 60-day Connecticut Chemosensory Clinical Research Center test scores and the inflammatory markers assessed. CONCLUSION: Olfactory disturbances appear to have little prognostic value in predicting the severity of coronavirus disease 2019 compared to D-dimer, ferritin, procalcitonin and neutrophil-to-lymphocyte ratio. The lack of correlation between the severity and duration of olfactory disturbances and serum levels of inflammatory markers seems to further suggest that the pathogenetic mechanisms underlying the loss of smell in coronavirus disease 2019 patients are related to local rather than systemic inflammatory factors.

Does Angiotensin II receptor blockers increase the risk of SARS-CoV-2 infection? A real-life experience.

OBJECTIVE: Since the start of the COVID-19 pandemic, millions of people have been infected with thousands of deaths. Few data regarding factors that increase the risk of infection are available. Our study aimed to evaluate all people living in retirement homes (PLRNH) and identify factors that could increase infection risk in a close community. MATERIALS AND METHODS: We conducted a retrospective study enrolling all PLRNH, where at least one SARS-CoV-2 infected person was present. Variables were compared with Student's t-test or Pearson chi-square test as appropriate. Uni- and multivariate analyses were conducted to evaluate variables' influence on the infection. RESULTS: We included 452 PLRNH; 144 (31.7%) were male, with a mean age of 82.2±8.6 years. People with a positive swab for SARS-CoV-2 were 306 (67.4%). A significant difference between SARS-CoV-2 infected and not infected was observed in the percentage of those receiving chronic treatment with Angiotensin II receptor blockers (ARBs) (18.6% vs. 9.5%, p=0.012). On the contrary, there was no difference in the proportion of those receiving ACE inhibitors (ACE-I) (21.2% vs. 23.6%, p=0.562). At multivariate analysis, people with mental illness and cancer had an increased risk of being infected. Furthermore, receiving ARBs as a chronic treatment was an independent predictor of infection risk [OR 1.95 (95% CI 1.03-3.72) p=0.041]. CONCLUSIONS: Our data suggest that, in close communities, such as retirement nursing homes, the receipt of ARBs increased the risk of acquiring SARS-CoV-2 infection. However, before changing an important chronic treatment in a fragile population, such as the elderly living in retirement nursing homes, clinicians should carefully evaluate the risk-benefit ratio.

Clinical features, laboratory findings and predictors of death in hospitalized patients with COVID-19 in Sardinia, Italy.

OBJECTIVE: Since December 2019, when the first SARS-CoV2 infections have been reported, the number of cases has increased exponentially. In our University Hospital Unit, the first patient with COVID-19 was admitted on the 8th of March 2020. We aimed to investigate the predictors of death among inpatients with COVID-19. MATERIALS AND METHODS: We performed a retrospective, monocentric study, consecutively enrolling patients with SARS-CoV2 infection. Clinical, laboratory, and radiological data were collected from the 8th of March to the 8th of April 2020. We aimed to describe the most frequent clinical and laboratory features and predictors of death among patients admitted to our Unit. RESULTS: 87 patients were enrolled, 56 (64.4%) were male, with a median age of 72 (IQR 62.5-83.5) years. The majority of our population had at least one comorbidity in their medical anamnesis. Hypertension and cardiovascular disease were the most frequent, followed by obesity. Eighty (92%) patients had at least one symptom, whereas 7 (8%) were asymptomatic. The most common symptoms were fever and dyspnoea. Overall, 53 patients had lung disease confirmed at CT scan (60.9%). Twenty-five (28.7%) deaths occurred. Statistically significant predictors of death at multivariate analysis were lymphocytes count <900 cells/mm3, moderate ARDS, and lack of compliance at baseline. CONCLUSIONS: This is the first Italian experience available. Our results seem to be in line with international literature. As highlighted by our data, more studies are needed to investigate the role of lymphocytes subsets, CT scan values. Furthermore, therapy choice and timing in this challenging setting should be urgently investigated in randomized clinical trials.

The additional role of 18F-FDG PET/CT in prosthetic valve endocarditis.

OBJECTIVE: The purpose of the present review is an update on the diagnosis of prosthetic valve endocarditis (PVE), evaluating the additional value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) to the standard modified DUKE criteria on which for a long time is based the diagnostic strategy of the disease. MATERIALS AND METHODS: We did a comprehensive research on the studies reported in the literature and regarding the employment of 18F-FDG PET/CT in the early diagnosis of PVE in patients with suspected disease. Scientific databases have been examined such as Medline and PubMed, followed by a review of citations and reference lists. The research included the following terms: infective endocarditis, prosthetic heart valve and cardiac valve replacement infections, 18F-FDG PET/CT and endocarditis. RESULTS: The recent studies reported in the literature on the PVE diagnostic approaches showed elevated sensitivity and specificity values of 18F-FDG PET/CT ranging from 73 to 96.6% and from 80 to 94%, respectively, reducing the number of misdiagnosed patients. The usefulness of the radioisotopic procedure is even more important when the other diagnostic conventional diagnostic tools, such as echocardiography, are inconclusive or negative in patients in whom the diagnosis of PVE is definitively ascertained. However, false negative and positive results of 18F-FDG PET/CT were also ascertained in some studies interfering with image interpretation even if such limitation can be reduced with an adequate patient preparation, with a better knowledge of clinical course of the disease, of the treatment in progress and of the different technical aspects of the method. CONCLUSIONS: In different studies reported in the literature, 18F-FDG PET/CT proved to improve the diagnostic accuracy of the conventional modified DUKE criteria in patients with suspected IE, and in particular with PVE, giving the highest diagnostic performance and providing additional diagnostic benefits. Thus, the radioisotopic hybrid procedure should be included in the diagnostic protocol of PVE as complementary tool to modified DUKE criteria. Finally, the usefulness of 18F-FDG PET/CT in monitoring the response to antibiotic therapy, although the few data reported in the literature are encouraging, needs more numerous studies and with a major number of cases.

Body fat changes in HIV patients on highly active antiretroviral therapy (HAART): a longitudinal DEXA study.

OBJECTIVE: We aimed to quantitatively evaluate body fat composition in a group of HIV patients treated with Highly Active Anti-retroviral Therapy (HAART) to ascertain both fat loss and fat distribution changes and to identify possible therapeutic and host related associated risk factors. PATIENTS AND METHODS: A total of 180 patients with available total body DEXA scan were assigned to a) Group 1, with clinically evident body fat changes, (BFC) and b) Group 2, without BFC. Clinical and immunovirologic data were collected. We used Student t-test and x2 or Fisher exact test to compare the characteristics of the two groups. Paired t-test was used to compare basal and follow-up data. The relationships between variables were evaluated by calculating Pearson's correlation coefficient and its significance. RESULTS: HAART duration was significantly (p<0.0001) higher for patients in Group 1 than in Group 2, as well as PI (p<0.02) and NRTI (p<0.002) therapy duration. Current CD4 count and CD4 rise from nadir resulted significantly higher in Group 1 than in Group 2 (p<0.02 and 0.006, respectively). Whole Body Fat (WBF), Peripheral Fat (PF) and Leg (L) fat negatively correlated with PI and NRTI therapy duration, while Trunk Fat (TF)/PF positively correlated with PI and NNRTI duration. No significant correlation was found, instead, with NNRTI therapy duration. At 5-year follow-up, we registered a further increase in TF, Arms (A) and L fat, especially in PI-treated patients. CONCLUSIONS: Body fat changes should always be considered when dealing with HIV-affected patients on HAART. The fat loss seemed to involve mainly peripheral regions, while fat accumulation tendency occurred in the trunk.

Underserved populations and bacterial and protozoal sexually transmitted infections: a lost health-care opportunity.

OBJECTIVE: The purpose of our review is an update about the burden of sexually transmitted infections (STIs) among various types of underserved populations, such as migrants, substance abusers, homeless and incarcerated inmates. First-line test and treatment based on the latest available evidence according to the revised guidelines of Centers for Disease Control and Prevention have also been considered. MATERIALS AND METHODS: We performed a comprehensive research using scientific databases such as Medline and Pubmed, followed by a review of citations and reference list. A consultation with other experts in the management of the various subpopulations was also conducted. RESULTS: Health-care is often influenced by social determinants, which play a vital role in the diffusion of STIs. The consequence is a socio-economical and ethnic disparity in the rate of STIs. Early screening and treatment of STIs should be implemented in clinical practice, starting from marginalized social groups, which are the most affected by this health problem. CONCLUSIONS: In the literature, there are very few papers containing information on STIs prevalence in various types of underserved populations, such as migrants, substance abusers, homeless and incarcerated inmates. The availability of more accurate epidemiological data is needed. In these groups, the most relevant barrier is the lower perception of health-care need, with an underestimation of risk and symptoms of STIs, causing a retard of diagnosis and health-care provision and use. For these populations, targeted interventions are needed, particularly on unaware people, responsible for most STIs transmissions.

The burden of HIV-associated neurocognitive disorder (HAND) in post-HAART era: a multidisciplinary review of the literature.

OBJECTIVE: The purpose of the present multidisciplinary review is to give an updated insight into the most recent findings regarding the pathophysiology, diagnosis and therapeutics of HIV-associated neurocognitive disorder (HAND). MATERIALS AND METHODS: We performed a comprehensive search, through electronic databases (Pubmed - MEDLINE) and search engines (Google Scholar), of peer-reviewed publications (articles and reviews) and conferences proceedings on HAND pathophysiology, diagnosis, and therapy, from 1999 to 2016. RESULTS: It seems to be increasingly clear that neurodegeneration in HIV-1 affected patients is a multi-faceted disease involving numerous factors, from chronic inflammation to central nervous system (CNS) compartmentalization of HIV. Diagnosis of HAND may benefit from both laboratory analysis and advanced specific neuroimaging techniques. As regards HAND therapy, modified HAART combinations and simplification strategies have been tested, while novel exciting frontiers seem to involve the use of nanoparticles with the ability to cross the Blood-Brain Barrier (BBB). CONCLUSIONS: Albeit highly active antiretroviral therapy (HAART) allowed a major decrease in morbidity and mortality for AIDS patients, CNS involvement still represents a challenge in HIV patients even today, affecting up to 50% of patients with access to combination antiretroviral therapy (cART). Future studies will have to focus on CNS compartmentalization, drugs' ability to penetrate and suppress viral replication in this compartment, and on new approaches to reduce HIV-associated neuroinflammation.

Optimal efficacy of interferon-free HCV retreatment after protease inhibitor failure in real life.

OBJECTIVES: First-generation protease-inhibitors (PIs) have suboptimal efficacy in GT-1 patients with advanced liver disease, and patients experiencing treatment failure may require urgent retreatment. Our objective was to analyse the real-life efficacy of interferon (IFN)-free retreatment after PI-failure, and the role of genotypic-resistance-testing (GRT) in guiding retreatment choice. METHODS: In this multi-centre observational study, patients retreated with IFN-free regimens after first-generation PI-failure (telaprevir-boceprevir-simeprevir) were included. Sustained-virological-response (SVR) was evaluated at week 12 of follow-up. GRT was performed by population-sequencing. RESULTS: After PI-failure, 121 patients (cirrhotic=86.8%) were retreated following three different strategies: A) with 'GRT-guided' regimens (N=18); B) with 'AASLD/EASL recommended, not GRT-guided' regimens (N=72); C) with 'not recommended, not GRT-guided' regimens (N=31). Overall SVR rate was 91%, but all 18 patients treated with 'GRT-guided' regimens reached SVR (100%), despite heterogeneity in treatment duration, use of PI and ribavirin, versus 68/72 patients (94.4%) receiving 'AASLD/EASL recommended, not GRT-guided' regimens. SVR was strongly reduced (77.4%) among the 31 patients who received a 'not recommended, not GRT-guided regimen' (p <0.01). Among 37 patients retreated with a PI, SVR rate was 89.2% (33/37). Four GT-1a cirrhotic patients failed an option (C) simeprevir-containing treatment; three out of four had a baseline R155K NS3-RAS. All seven patients treated with paritaprevir-containing regimens reached SVR, regardless of treatment duration and performance of a baseline-GRT. CONCLUSION: Retreatment of PI-experienced patients can induce maximal SVR rates in real life. Baseline-GRT could help to optimize retreatment strategy, allowing PIs to be reconsidered when chosen after a RASs evaluation.

Immune response induced by Epstein-Barr virus and Mycobacterium avium subsp. paratuberculosis peptides in current and past infectious mononucleosis: a risk for multiple sclerosis?

BACKGROUND AND PURPOSE: Infectious mononucleosis (IM) caused by Epstein-Barr virus (EBV) has been associated with increased risk of multiple sclerosis (MS). However, the mechanism linking these pathologies is unclear. Different reports indicate the association of EBV, and recently Mycobacterium avium subsp. paratuberculosis (MAP), with MS. For a better understanding of the role of these pathogens, the host response induced by selected antigenic peptides in subjects with a history of IM that significantly increases the risk of MS was investigated. METHODS: Both humoral and cell-mediated response against peptides able to induce a specific immune activation in MS patients deriving from lytic and latent EBV antigens BOLF1(305-320), EBNA1(400-413), from MAP MAP_4027(18-32), MAP_0106c(121-132) and from human proteins IRF5(424-434) and MBP(85-98) in subjects with current and past IM were examined. RESULTS: EBNA1 and MAP_0106c peptides were able to induce a humoral immune response in subjects with a history of clinical IM in an independent manner. Moreover, these peptides were capable of inducing pro-inflammatory cytokine interferon γ by CD4+ and CD8+ T lymphocytes and interleukin 6 and tumour necrosis factor α by CD14+ monocyte cells. CONCLUSION: Our results highlight that EBV and MAP may be involved independently in the same causal process leading to MS in subjects with a history of IM.

HCV NS3 sequencing as a reliable and clinically useful tool for the assessment of genotype and resistance mutations for clinical samples with different HCV-RNA levels.

OBJECTIVES: This study aims to evaluate the reliability and clinical utility of NS3 sequencing in hepatitis C virus (HCV) 1-infected patients who were candidates to start a PI-containing regimen. METHODS: NS3 protease sequencing was performed by in-house-developed HCV-1 subtype-specific protocols. Phylogenetic analysis was used to test sequencing reliability and concordance with previous genotype/subtype assignment by commercial genotyping assays. RESULTS: Five hundred and sixty-seven HCV plasma samples with quantifiable HCV-RNA from 326 HCV-infected patients were collected between 2011 and 2014. Overall, the success rate of NS3 sequencing was 88.9%. The success rate between the two subtype protocols (HCV-1a/HCV-1b) was similarly high for samples with HCV-RNA >3 log IU/mL (>92% success rate), while it was slightly lower for HCV-1a samples with HCV-RNA ≤3 log IU/mL compared with HCV-1b samples. Phylogenetic analysis confirmed the genotype/subtype given by commercial genotyping assays in 92.9% (303/326) of cases analysed. In the remaining 23 cases (7.1%), 1 was HCV-1g (previously defined as subtype 1a), 1 was HCV-4d (previously defined as genotype 1b) and 1 was HCV-1b (previously defined as genotype 2a/2c). In the other cases, NS3 sequencing precisely resolved the either previous undetermined/discordant subtype 1 or double genotype/subtype assignment by commercial genotyping assays. Resistance-associated variants (RAVs) to PI were detected in 31.0% of samples. This prevalence changed according to PI experience (17.1% in PI-naive patients versus 79.2% in boceprevir/telaprevir/simeprevir-failing patients). Among 96 patients with available virological outcome following boceprevir/telaprevir treatment, a trend of association between baseline NS3 RAVs and virological failure was observed (particularly for HCV-1a-infected patients: 3/21 failing patients versus 0/22 achieving sustained virological response; P = 0.11). CONCLUSIONS: HCV-NS3 sequencing provides reliable results and at the same time gives two clinically relevant pieces of information: a correct subtype/genotype assignment and the detection of variants that may interfere with the efficacy of PI.

Different impact of NNRTI and PI-including HAART on bone mineral density loss in HIV-infected patients.

OBJECTIVE: To evaluate the changes in Bone Mineral Density (BMD) and bone remodelling markers in a group of HIV patients treated with HAART and controlled in a long follow-up and to identify possible risk factors for accelerated bone mass loss. PATIENTS AND METHODS: In a series of 172 HIV patients treated with HAART a total of 67 patients (44 males and 33 females) underwent repeated bone mineral density measurement by DEXA in lumbar spine and in femur; the patients were classified according to T-score WHO criteria. Serum bone alkaline phosphatase (BAP), by IRMA, and urine pyridinoline/deoxypyridinoline (PYD&DPD), by EIA, were also assayed in all cases. RESULTS: At baseline, 62/67 patients were on HAART, while 5 were naïve; 44.8% were previous intravenous drug users (IVDU), 46.3% heterosexual and 8.9% homosexual, mean age being 40.2 ± 6.5 years, and 23.9% had previous AIDS diagnosis. Fifteen/67 (22.4%) of treated patients had osteoporosis and 25/67 (37.3%) osteopenia in spine and/or femur including 3 naïve, 27/67 (40.3%), including 2 naïve, had normal BMD in both sites. Fifty-one/67 patients were monitored during follow-up (56.8 ± 5.3 months); 27 (52.9%) of these (Group 1), received protease inhibitors (PI) and 24 (47.1%), including naïve, (Group 2) received not nucleoside reverse transcriptase inhibitors (NNRTI) for > 50% of follow-up period. In Group 1 patients, BMD reduction was observed after follow-up in respect of basal condition in both spine and femur, but significantly (p = 0.011) only for the latter. However, mean BMD values remained stable in both sites in Group 2 patients. Basal BAP and PYD&DPD levels were higher in Group 1 than Group 2, but not significantly. Moreover, only PYD&DPD levels at the follow-up evaluation were significantly (p = 0.031) higher in Group 1 than Group 2. Of the remaining 16/67 patients with osteoporosis/osteopenia, 10 received PI and 6 NNRTI and were treated with therapies that could increase bone density, in particular, 9 with Alendronate/Vitamin D/Calcium and 7 with only vitamin D/calcium; these patients were excluded from statistical analysis of 51 Group 1/Group 2 cases. In the 16 patients, after these specific treatments, mean spine and femur BMD increased over time, but significantly only in those cases including alendronate in their protocol. CONCLUSIONS: The study showed that in HIV patients on HAART BMD decrease, even osteoporosis, can be present persisting over time, particularly in PI in respect of NNRTI treated patients. The pathogenesis is probably multifactorial, the different antiviral drugs seeming to differently affect bone metabolism. Alendronate/Vitamin D/Calcium therapy can be useful to slow down bone mass loss and also improve osteoporosis/osteopenia conditions, thus, reducing fracture risk also continuing HAART.

HIV treatment and care among Italian inmates: a one-month point survey.

BACKGROUND: HIV infection, with an estimated prevalence be between 2 and 50 times those of the general adult population is a major health challenge for prison authorities worldwide. Since no nationwide surveillance system is present in Italy, data on HIV prevalence and treatment in prisons are limited to only a few and small observational studies. We aimed to estimate HIV prevalence and obtain an overview on diagnostic and therapeutic activities concerning HIV infection in the Italian penitentiary system. METHODS: We piloted a multi-centre cross-sectional study investigating the prevalence of HIV infection and assessing HIV-related medical activities in Italian correctional institutions. RESULTS: A total of 15,675 prisoners from 25 institutions, accounting for approximately one-fourth of the prison inmates in Italy, were included in the study, of whom, 97.7 % were males, 37.1 % foreigners and 27 % had a history of intravenous drug addiction. HIV-tests were available in 42.3 % of the total population, with a known HIV Infection proportion of 5.1 %. In the month prior to the study, 604 of the 1,764 subjects who entered prison were tested for HIV, with a HIV-positive prevalence of 3.3 %. Among the 338 HIV-positive prisoners, 81.4 % were under antiretroviral treatment and 73.5 % showed undetectable HIV-RNA. In 23/338 (6.8 %) a coinfection with HBV and in 189/338 (55.9 %) with HCV was also present. Among the 67 (19.8 %) inmates with HIV who did not receive HIV treatment, 13 (19.5 %) had T-CD4+ count <350 cells/mm(3) and 9 (69.2 %) of these had refused the treatment. The majority of the inmates with HIV-infection were on a PI-based (62.5 %) or on NNRTIs-based (24.4 %) regimen. Only a minority of patients received once daily regimens (17.2 %). CONCLUSIONS: Although clinical and therapeutic management of HIV infection remains difficult in Italian prisons, diagnostics, treatment and care were offered to the majority of HIV-infected inmates. Specific programs should be directed towards the prison population and strict cooperation between prison and health institutions is needed to increase HIV treatment.

Undetectable HCV-RNA at treatment-week 8 results in high-sustained virological response in HCV G1 treatment-experienced patients with advanced liver disease: the International Italian/Spanish Boceprevir/Peginterferon/Ribavirin Name Patients Program.

In many countries, first-generation protease inhibitors (PIs)/peginterferon/ribavirin (P/R) still represent the only treatment option for HCV-infected patients. Subjects with advanced disease and previous failure to P/R urgently need therapy, but they are under-represented in clinical trials. All treatment-experienced F3/4 Metavir patients who received boceprevir (BOC)+P/R in the Italian-Spanish Name Patient Program have been included in this study. Multivariate logistic regression analysis (MLR) was used to identify baseline and on-treatment predictors of SVR and adverse events (AEs). Four hundred and sixteen patients, mean age 57.7 (range 25-78 years), 70% males, 69.5% (289/416) F4, 14% (41/289) Child-Pugh class A6, 24% (70/289) with varices and 42% (173/416) prior null responders to P/R, were analysed. Overall, SVR rate (all 381 patients who received one dose of BOC) was 49%, (58% in F3, 45% in F4, 61% in relapsers, 51% in partial, 38% in null responders, and 72% in subjects with undetectable HCV-RNA at treatment-week (TW)8. Among patients with TW8 HCV-RNA ≥ 1000 IU/L, SVR was 8% (negative predictive value = 92%). Death occurred in 3 (0.8%) patients, while decompensation and infections were observed in 2.9% and 11%, respectively. At MLR, SVR predictors were TW4 HCV-RNA ≥ 1log10 -decline from baseline, undetectable TW8 HCV-RNA, prior relapse, albumin levels ≥3.5 g/dL and platelet counts ≥100 000/µL. Metavir F4, Child-Pugh A6, albumin, platelets, age and female gender were associated with serious and haematological AEs. Among treatment-experienced patients with advanced liver disease eligible for IFN-based therapy, TW8 HCV-RNA characterised the subset with either high or poor likelihood of achieving SVR. Using TW8 HCV-RNA as a futility rule, BOC/P/R appears to have a favourable benefit-risk profile.

HPV infection in HIV-positive females: the need for cervical cancer screening including HPV-DNA detection despite successful HAART.

PURPOSE: To identify the presence of Human Papilloma Virus (HPV) infection and evaluate the role of Highly Active Antiretroviral Treatment (HAART) in patients with HIV-HPV co-infection. We also compared cytological screening results with HPV-DNA detection to implement screening programs and prevention of invasive cervical cancer (ICC) in HIV-infected females. PATIENTS AND METHODS: We enrolled HIV-infected females presenting for routine clinical evaluation. HPV-DNA of high/intermediate and low-risk types was detected from cervical specimens by nucleic acid hybridization assay with signal-amplification. Patients were divided into two groups according to the presence of HPV co-infection (HPV+) or not (HPV-). RESULTS: We enrolled 57 HIV-infected females. Median age was 40 (IQR 35-44) years, mean CD4 count was 547 ± 227 cells/mm(3), 45 (78.9%) had undetectable HIV-RNA and 52 (91.2%) received HAART. Globally, 19/57 (33.3%) patients were HPV-infected, 16/57 (28.1%) with high/intermediate and 3/57 (5.3%) with low-risk types. Five of the 19 (26.3%) HPV+ patients carried both types. Correlating high-risk genotype HPV-DNA detection with cytology, 17.5% of women with negative cytology, 36.4% with ASCUS (Atypical Squamous Cells of Uncertain Significance) and 83.4% of women with positive cytology (50% of LSIL: low-grade squamous intraepithelial lesion and 100% of HSIL: high grade SIL) were HPV positive. No statistical difference when comparing HPV+ and HPV-patients in age, CD4 cell count, in the proportion of previous intravenous-drug use, previous AIDS and of those receiving HAART with undetectable HIV-RNA was observed. CONCLUSIONS: Cervical cancer screening including HPV-DNA detection should be implemented in HIV infected females across Europe, also when receiving successful HAART, to early identify the HIV patients at risk for ICC to be submitted to more frequent follow up and proper treatment.

Proteomic characterization of hepatitis C eradication: enzyme switch in the healing liver.

Lipid pathway impairment, decrease in the antioxidant pool and downregulation in amino-acid metabolism are just some of the metabolic variations attributed to chronic HCV infection. All of them have been studied separately, mainly in animal models. Thanks to proteomic analysis we managed to describe (for the fist time to the best of our knowledge), in vivo and in humans, the metabolic alterations caused by HCV, and the recovery of the same alterations during HCV treatment. We performed proteomic analysis on liver specimens of a 28-year-old woman affected by hepatitis C genotype 1a, alcoholism and diabetes mellitus type 1, before and after antiviral treatment with pegylated interferon alpha 2b and ribavirin. The subject, thanks to a patient-tailored therapy, reached Sustained Virological Response. Throughout the treatment period the patient was monitored with subsequent biochemical, clinical and psychological examinations. The data obtained by the patient's close monitoring suggest a direct interaction between insulin resistance and an active HCV genotype 1 infection, with a leading role played by the infection, and not by insulin resistance, as demonstrated by the sharp fall of the insulin units needed per day during treatment. The proteomic analysis showed that after therapy, a downregulation of enzymes involved in amino acid metabolism, glycolysis/gluconeogenesis and alcohol catabolism takes place, the latter probably due to cessation of alcohol abuse. On the contrary, the metabolic pathways linked to metabolism of the reactive oxygen species were upregulated after therapy. Finally, a significant alteration in the pathway regulated by peroxisome proliferator-activated receptor alpha (PPARA), a major regulator of lipid metabolism in the liver, was reported. These "real time" data confirm in vivo, in humans, that during HCV infection, the pathways related to fatty acids, glucose metabolism and free radical scavenging are inhibited. The same enzyme deficit is completely recovered after HCV eradication.

Chronic obstructive pulmonary disease: an emerging comorbidity in HIV-infected patients in the HAART era?

PURPOSE: The objective of our study was to evaluate the presence of respiratory symptoms and chronic obstructive pulmonary disease (COPD) in a human immunodeficiency virus (HIV)-infected outpatient population and to further investigate the role of highly active antiretroviral therapy (HAART) and other possibly associated risk factors. METHODS: We consecutively enrolled in a cross-sectional study HIV-infected patients and HIV-negative age, sex and smoking status matched controls. All participants completed a questionnaire for pulmonary symptoms and underwent a complete spirometry. RESULTS: We enrolled 111 HIV-infected patients and 65 HIV-negative age- and sex-matched controls. HIV-infected patients had a significantly higher prevalence of any respiratory symptom (p = 0.002), cough (p = 0.006) and dyspnoea (p = 0.02). HIV-infected patients also had a significantly higher prevalence of COPD in respect of HIV-negative controls (p = 0.008). Furthermore, HIV-infected individuals had significantly (p = 0.002) lower forced expiratory volume at one second (FEV1) and FEV1/forced vital capacity (FVC) ratio (Tiffeneau index) (p = 0.028), whereas the total lung capacity (TLC) was significantly higher (p = 0.018). In the multivariate analysis, significant predictors of respiratory symptoms were current smoking [adjusted odds ratio (AOR) 11.18; 95 % confidence interval (CI) 3.89-32.12] and previous bacterial pneumonia (AOR 4.41; 95 % CI 1.13-17.13), whereas the only significant predictor of COPD was current smoking (AOR 5.94; 95 % CI 1.77-19.96). HAART receipt was not associated with respiratory symptoms nor with COPD. CONCLUSIONS: We evidenced a high prevalence of respiratory symptoms and COPD among HIV-infected patients. HIV infection, current cigarette smoking and previous bacterial pneumonia seem to play a significant role in the development of respiratory symptoms and COPD. Thus, our results suggest that the most at-risk HIV-infected patients should be screened for COPD to early identify those who may need specific treatment.