The emergence of drug‐resistance mutations in HIV‐1 integrase of patients receiving HAART salvage regimens including raltegravir was investigated in 11 heavily pretreated patients (median number of treatment failures 12, range 5–22) within an expanded access program in Pavia, Italy. HIV‐1 RNA levels in plasma, CD4+ T‐cell counts and sequencing of HIV‐1 reverse transcriptase (RT), protease (PR), gp41, and integrase genes were performed at baseline and after 1, 2, 3, 6, and 12 months. The treatment baseline median HIV‐1 RNA levels in plasma decreased from 7,510 (range 118–407,107) to <50 copies/ml (range <50–7,562), while median CD4+ T‐cell counts remained unchanged (from 212 cells/µl, range 10–764 to 262 cells/µl, range 13–760). Mutations at positions involved in raltegravir resistance (E92G, G140S, Q148H, and N155H) were detected in 4 of 11 (36.3%) patients as early as 1 month after initiating salvage HAART. Of note, the E → G change at codon 92 was not reported previously. In two patients with raltegravir resistance, the simultaneous appearance of additional mutations (Y143R and E170A) with an unclear impact on susceptibility to raltegravir or on integrase activity was observed. It is concluded that raltegravir resistant HIV‐1 strains may emerge as early as 1 month after initiating HAART salvage regimens. A new mutation associated with the emergence of raltegravir resistance is described, and the simultaneous appearance of primary and secondary mutations was observed. The effect of single and multiple mutations on integrase activity, raltegravir susceptibility, and on the capacity of viral replication remains to be elucidated. J. Med. Virol. 82:116–122, 2010. © 2009 Wiley‐Liss, Inc.

BackgroundThe aim of the present study is to test in the feasibility of a screening programme for HCV infection in an Italian prison and to evaluate the treatment outcomes.MethodSingle-centre cross-sectional study carried out in Milan-Opera. The HCV infection prevalence was calculated on the imprisoned population on the January 31 2006, the data on treatment over the following 2 years. Treatment option offered to HCV chronically infected patients was then analysed, reasons for not being treated was evaluated.ResultsOf the 965 inmates, 695 were enrolled in the study, 682 (98%) were males, the median age was 43 years. There were 131 (18.8%) foreigners and 564 (81.2%) Italians. HCV seroprevalence was 22.4%(95% CI:19.4%-25.7%), 60 subjects (38.4%) being HIV co-infected too. Prevalence of HCV infection was significantly higher in HIVAb positive (89.6%; 95% CI:79.7%-95.7%) than in HIVAb negative (15.15%; 95% CI 12.6%-18.3%) (p<0.001). Among Italian inmates HCVAb positivity was significantly higher than among foreigners (p=0.0154). Among HCVAb positive patients, 135 subjects were HCV-RNA positive. Forty-seven (36%) had major clinical contraindication to treatment, 18 (13%) refused the treatment, 7 (5%) moved to other Institute and 27 (20%) were not evaluated by infectious disease specialists. Fifteen patients (43%) who received treatment were considered responders, 9 (26%) were non responders/relapsers, 6 (17%) interrupted treatment due to side effects and 5 (14%) were released during treatment and lost in follow-up.ConclusionsThis study indicates that the proportion of patients in a prison setting receiving diagnosis and treatment for HCV infection remained low.

Observational retrospective study to evaluate the etiology, the outcome and the risk factors of bloodstream infections (BSIs) in patients with liver disease. One hundred and forty-eight BSIs were diagnosed (infection rate: 0.60 per 100 days of hospital stay), 62 BSIs (41.9 %) were associated with Gram-positive bacteria (infection rate: 0.25 per 100 days of hospital stay) and 80 (54.4 %) with Gram-negative bacteria (infection rate: 0.32 per 100 days of hospital stay). Admission-associated mortality was higher in patients with BSI than in those without BSI (20.6 versus 5.0 %, p < 0.001). Patients with cirrhosis had an increased risk to develop a BSI compared with patients with chronic hepatitis, specifically for Gram-positive (and Staphylococcus spp)-related BSI.

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We are conducting a multicenter, randomized, controlled, prospective, open trial to evaluate both the efficacy and toxicity of nevirapine (NVP) (given twice [BID] or once daily [QD]) in virologically-suppressed patients on a PIbased HAART. NVP BID dosing is maintained for 2 months after the switch in both groups. MethodsPatients with >6 months of plasma HIV-RNA (pVL) undetectability (<50 copies/mL) while on therapy with a PI (boosted or unboosted) plus two NRTIs were considered for enrolment. Co-infection with HCV and/or HBV was allowed. All patients were to receive NVP 400 mg/day on a bid schedule for 2 months and then should be randomized to continue (group A) or to switch to a QD schedule (group B). The NRTI backbone could either be maintained or changed during the study. Summary of resultsThe study enrolled 126 patients (63 in each group). Database was frozen on June 30, 2008, and an interim analysis was done on 119 patients whose data are available on the internet-based CRFs. Males are 90%, mean age was 45 ± 8.9 years, 93.1% are Caucasians, 37.8% had AIDS, 24.7% are HCV+. HIV-RNA pVL result undetectable since mean of 28 months before switch. At baseline CD4s were 531 ± 262/mm 3 , total cholesterol 202 ± 49.2 mg/dL, triglycerides 216 ± 140.3 mg/dL, ALT 33 ± 22.6 U/L, and gamma-GT 53 ± 69.6 U/L (all means ± SD). No statistically significant differences were present between groups at switch. After 6 months, mean values in group A vs. B were respectively: CD4s 578 ± 290 and 573 ± 261/mm 3 ; cholesterol 204 ± 42.6 and 195 ± 39.9 mg/dL; triglycerides 135 ± 69.3 and 142 ± 81.7 mg/dL; ALT 51 ± 47.4 and 50 ± 44.3 U/L; gamma-GT 124 ± 120.9 and 123 ± 176.9 U/L (p values: all NS). We have so far recorded five virological failures (four in group A -two at 3rd and two at 4th month, one in B at 4th month). Five patients (three in group A; two in group B) had grade-4 adverse events (AEs) in the first 2 months after switch (when both groups were treated with NVP bid): three episodes of hepatotoxicity (two in HCV+), one rash (in a black woman), and one for headache and dizziness. Three additional hepatotoxic grade-4 AEs occurred afterwards: two in group A (6th month) and one in B (3rd month), all in patients without HCV/HBV co-infections.

To assess the efficacy and the tolerability of once-daily (QD) versus twice-daily (BID) nevirapine (NVP)-based highly active antiretroviral therapy (HAART) in virologically suppressed, HIV-positive patients switched from protease inhibitor (PI)-based HAART. Eligible patients were enrolled in the multicenter trial if HIV RNA levels were <50 copies/mL for ³6 months prior. Patients were switched from a PI to NVP 200 mg BID for 2 months, and then randomized to continue with that regimen (group A) or NVP 400 mg QD (group B) for a further 10 months. Virological efficacy (primary endpoint) and tolerability/toxicity were evaluated according to an intention-to-treat analysis. A total of 126 patients (63 per group) were enrolled. Withdrawals from the study (any reason) numbered 15 in group A and 14 in B, virological failures numbered 5 and 2, respectively, and there were 4 cases of adverse events in each group (all p = NS). Mean alanine aminotransaminase (ALT) and gamma-glutamyl transpeptidase (γ-GT) level increases were significant for the whole cohort (33.2±22.9 to 43.3±29.1, p < 0.001; 57.3±72 to 109±131 U/L, p < 0.0002, respectively), but there were no differences between the two groups. Apparently, no significant differences between the QD and BID NVP groups were found, in terms of virological failures or tolerability/toxicity. The switch to NVP may be safely pursued with a QD schedule.