Randomized clinical trial on efficacy of fixed-dose efavirenz/tenofovir/emtricitabine on alternate days versus continuous treatment.

OBJECTIVE: Antiretrovirals with long half-lives, such as tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) and efavirenz (EFV), are suitable for reduced frequency dosing, with potential for improved adherence and reduced toxicity and costs. The objective of this study was to investigate the noninferiority of the TDF/FTC/EFV fixed-dose combination on alternate-days versus standard regimen in virologically suppressed patients. DESIGN: A randomized-controlled open-label noninferiority trial enrolling HIV-1-infected patients treated for at least 6 months with TDF/FTC/EFV fixed-dose combination, virologically suppressed (<40 HIV-RNA copies/ml) with EFV plasma concentrations greater than 1000 ng/ml, were randomized to maintain TDF/FTC/EFV standard-of-care regimen (SOC, Arm A) or to switch to TDF/FTC/EFV on AlTernAte Days (ATAD, Arm B). METHODS: Primary end-point was the proportion of patients with less than 40 HIV-RNA copies/ml at week 48. RESULTS: One hundred and ninety-seven patients were randomized (98 in the SOC and 99 in the ATAD arm). One hundred and seventy-nine (90.3%) were men, median age 43.2 years, 133 (67.5%) MSM. CD4+ T-cell count at baseline was 706 cells/µl in SOC and 632 cells/µl in ATAD arm. At week 48, 95 (96.9%) patients in SOC and 93 (93.9%) in ATAD had a virological response (-3.0% overall risk difference, 95% CI: -8.86%/2.86%). Median change from baseline at week 48 in CD4+ T-cell count was 29.4 cells/µl (95% CI: 2.5/56.4) in SOC (P = 0.008) and 61.0 cells/µl (95% CI: 32.1/89.9) in ATAD (P < 0.001). Median change of EFV concentration at week 48 from baseline was -6.5 ng/ml (95% CI: -103/55) in SOC (P = 0.877) and -1124 ng/ml (95% CI: -1375/-928) in ATAD arm (P < 0.001). CONCLUSION: Despite a significant decrease of EFV exposure, TDF/FTC/EFV on ATAD was noninferior to SOC regimen through 48 weeks.

Evaluation of the Aptima(®) HIV-1 Quant Dx assay for HIV-1 RNA viral load detection and quantitation in plasma of HIV-1-infected individuals: A comparison with Abbott RealTime HIV-1 assay.

The Hologic Aptima(®) HIV-1 Quant Dx assay (Aptima HIV) is a real-time transcription-mediated amplification method CE-approved for use in diagnosis and monitoring of HIV-1 infection. The analytical performance of this new assay was compared to the FDA-approved Abbott RealTime HIV-1 (RealTime). The evaluation was performed using 220 clinical plasma samples, the WHO 3rd HIV-1 International Standard, and the QCMD HIV-1 RNA EQA. Concordance on qualitative results, correlation between quantitative results, accuracy, and reproducibility of viral load data were analyzed. The ability to measure HIV-1 subtypes was assessed on the second WHO International Reference Preparation Panel for HIV-1 Subtypes. With clinical samples, inter-assay agreement for qualitative results was high (91.8%) with Cohen's kappa statistic equal to 0.836. For samples with quantitative results in both assays (n = 93), Lin's concordance correlation coefficient was 0.980 (P < 0.0001) and mean differences of measurement, conducted according to Bland-Altman method, was low (0.115 log10 copies/ml). The Aptima HIV quantified the WHO 3rd HIV-1 International Standard diluted from 2000 to 31 cp/ml (5,700-88 IU/ml) at expected values with excellent linearity (R(2) > 0.970) and showed higher sensitivity compared to RealTime being able to detect HIV-1 RNA in 10 out of 10 replicates containing down to 7 cp/ml (20 IU/ml). Reproducibility was very high, even at low HIV-1 RNA values. The Aptima HIV was able to detect and accurately quantify all the main HIV-1 subtypes in both reference panels and clinical samples. Besides excellent performance, Aptima HIV shows full automation, ease of use, and improved workflow compared to RealTime. J. Med. Virol. 88:1535-1544, 2016. © 2016 Wiley Periodicals, Inc.

a statistical model based on serological parameters for predicting occult HBV infection: implications for organ/ blood donations.

The transmission of hepatitis B virus by donors with occult HBV infection (OBI) is a threat for blood transfusion and organ/tissue transplantation. The risk of carrying HBV DNA is currently not predictable by simple serologic markers, while HBV DNA testing is not universally deployed. This study evaluated an integrated serologic approach for assessing this risk. Anti-HBc positive subjects (461 HIV-negative, 262 HIV-positive) were selected for the study. Serology was analyzed by a commercial CMIA technique. HBV DNA was analyzed by both commercial and home-brew real-time amplification assays. A penalized maximum likelihood logistic approach was used to analyze the data. In HBsAg-negative subjects (HIV-negative), anti-HBc signal/cut off values, the presence of anti-HBc IgM, the absence of anti-HBsAg, and the absence of anti-HCV were correlated to the probability of finding circulating HBV DNA. A model for predicting HBV DNA presence by 4 serological parameters is therefore proposed. The predictive value of the logistic model based on simple serologic markers may represent a reasonable tool for the assessment of HBV transmission risk by transfusion or organ/tissue donation in the context of limited resources and where nucleic acid testing is not performed. In addition, it may be helpful for assessing the risk of reactivation in immunosuppressed OBI patients.

Ability of two commercially available assays (Abbott RealTime HIV-1 and Roche Cobas AmpliPrep/Cobas TaqMan HIV-1 Version 2.0) to quantify low HIV-1 RNA Levels (<1,000 copies/milliliter): comparison with clinical samples and NIBSC working reagent for nucleic acid testing assays.

Concordance between molecular assays may be suboptimal at low HIV-1 viremia levels (<1,000 copies/ml); therefore, it may be difficult to define and compare virologic endpoints for successful and failed therapy. We compared two commercial assays (the Abbott RealTime HIV-1 and the Roche Cobas AmpliPrep/TaqMan HIV-1 version 2.0) for their ability to detect and quantify low viral loads. A comparison was performed using 167 residual clinical samples (with values ranging from "not detected" to 1,000 copies/ml, as measured by the Abbott assay) and the National Institute and Biological Standards and Control (NIBSC) HIV-1 RNA working reagent 1 for nucleic acid amplification techniques (NAT) assays (serially diluted to a range from 1 to 1,000 copies/ml). Quantitative results were compared using Lin's concordance correlation coefficient and a Bland-Altman plot. Concordance with the qualitative results was measured by Cohen's kappa statistic. With clinical samples, the degree of interassay concordance of the qualitative results at a 40-copies/ml HIV-1 RNA threshold was substantial (κ = 0.762); the correlation among the quantified samples was suboptimal (concordance correlation coefficient, 0.728; P < 0.0001); the mean difference of the values between the Roche and Abbott assays was 0.193 log10 copies/ml. Using the HIV-1 RNA working reagent 1 for NAT assays, the results provided by the Roche assay were, on average, 3 times higher than expected, while the Abbott assay showed high accuracy. The Roche assay was highly sensitive, being able to detect a level as low as 3.5 copies/ml HIV-1 RNA with 95% probability. The performance characteristics of each molecular assay should be taken into account when HIV-1 RNA threshold values for "virologic suppression," "virologic failure," "persistent low viral loads," etc., are defined and indicated in the support of clinical decisions.

No impact of interleukin-28B polymorphisms on spontaneous or drug-induced hepatitis delta virus clearance.

BACKGROUND: rs12979860 and rs8099917 interleukin-28B polymorphisms are associated with spontaneous or interferon-alpha induced hepatitis C clearance, "CC" and "TT" genotypes (respectively) being the most favourable. There are no data on the influence of interleukin-28B polymorphisms on hepatitis delta clearance in hepatitis B/D co-infected patients. AIMS: The present study explores the potential influence of both rs12979860 and rs8099917 polymorphisms on delta infection outcome. METHODS: Retrospective-longitudinal study on 55 European patients observed for at least 4 years, selected from a cohort of 439 subjects positive for hepatitis delta antibodies and hepatitis B core antibodies. The rate of spontaneous and interferon induced delta-RNA clearance was compared in interleukin-28B rs12979860 "CC" vs "non CC", and in rs8099917 "TT" vs "non TT" genotypes. RESULTS: Prevalence of rs12979860C allele was 60%, consistent with the reported prevalence in Italy (67%, p=0.128). No significant differences in spontaneous clearance rate were observed between rs12979860 "CC" and "non CC" genotypes (13.3% vs 7.5%, respectively, p=0.60), and between rs8099917 "TT" and "non-TT" genotypes (11.1 vs 7.1%, respectively, p=0.67). No differences were observed for interferon-induced delta-RNA clearance either. CONCLUSIONS: Our data suggest that interleukin-28B polymorphisms might not influence hepatitis delta clearance rate in either natural history or interferon-alpha response.

Temporal trend and characteristics of recent HIV-1 infections: application of an algorithm for the identification of recently acquired HIV-1 infections among newly diagnosed individuals over a 10-year period.

Identification of recent infections (RI) may contribute to improve the quality of human immunodeficiency virus (HIV) surveillance, monitoring ongoing transmission and planning and evaluating prevention programs. Our study applied an algorithm combining clinical and serological information to identify RI in individuals newly diagnosed with HIV in Rome, during the years 1999-2008, in order to describe the trend and characteristics of recently infected individuals. RI were documented seroconverters, or people with an HIV avidity index (AI)<0.80. Individuals with advanced infection (CD4 count <200 cells/?L or AIDS-defining illness) or with AI ?0.80 were considered long-standing infections. Overall, we observed 2,563 new HIV diagnoses. The algorithm was applied in 2124/2563 (82.9%). Of these, 355 were RI (16.7%). RI was found independently associated with calendar year (adjusted odds ratio [aOR]= 1.06, 95% confidence intervals [CI]=[CI 1.02-1.11], for every year of increase), HIV-risk category (men having sex with men: aOR=1.44, [CI 1.04-1.98]; injecting drug users: aOR=1.58, [CI 1.03-2.42] vs. heterosexuals), country of origin (foreign-born: vs Italians: aOR=0.46, [CI 0.33-0.62]), and recruitment site (inpatient vs outpatient clinic: aOR=0.49, [CI 0.37-0.66]). By the application of our algorithm we could characterize the pattern of ongoing HIV transmission, identifying groups needing more urgent prevention programs.

Cystic echinococcosis in a single tertiary care center in Rome, Italy.

BACKGROUND: Cystic echinococcosis (CE) is a chronic, clinically complex, and neglected disease. Its prevalence in Italy, a country of medium to high endemicity, remains poorly defined, as notification has long ceased to be mandatory. METHODS: We set up a retrospective cohort study involving all CE patients followed at our institute between January 2005 and December 2012. Demographical and clinical features were recorded and analyzed. RESULTS: CE was found in 28 patients (64.3%), mostly Italians from the central regions (50%), followed by subjects from the islands (33.3%) and Southern Italy (16.7%). Their median age was 45 years (IQR: 38.5-66.5), with Eastern Europeans being significantly younger (28 years, IQR: 19-39) than other patients (P ≤ 0.0001). A total of 149 cysts, mostly with hepatic localization (96%), were described. Based on the WHO classification, the cysts were mainly small (80.5%) and active (CE1 (73.8%); CE2 (7.4%)). Active cysts were more common in Eastern Europeans (85.7%) than Italians (66.7%). CONCLUSION: Our data confirm CE occurrence in Italy. We emphasize the importance to have a national CE registry, opportunely recently introduced. This is essential to assess CE prevalence in this country, implement appropriate control measures, and improve patient management.

Access to treatment for HBV infection and its consistency with 2008 European guidelines in a multicentre cross-sectional study of HIV/HBV co-infected patients in Italy.

BACKGROUND: A survey was performed in 2008 to evaluate the profiles of patients with chronic hepatitis B cared for by Italian Infectious Diseases Centers (IDCs). This analysis describes: i) factors associated with access to the anti-HBV treatment in a cohort of HIV/HBV co-infected patients cared for in tertiary centers of a developed country with comprehensive coverage under the National Health System (NHS); ii) consistency of current anti-HBV regimens with specific European guidelines in force at the time of the study and factors associated with the receipt of sub-optimal regimens. METHODS: The study focuses on 374 (87.6%) treated patients at some point in their life out of the 427 tested HIV/HBV positive. It is multicentre, cross-sectional in the design. To account for missing values, a Multiple Imputation method is used. RESULTS: Three hundred and thirty-four (89.3%) patients were currently treated. The most common current regimen was combination therapy of tenofovir (TDF) plus LAM/FTC (lamivudine/emtricitabine) (n = 235, 70.4%), as part of antiretroviral treatment. In the multivariate analysis, an increased chance of getting treated was independently associated with increasing years since HBV diagnosis (2-10 years, p <0.001; >10 years, p <0.001). Patients consistently treated with European AIDS Clinical Society (EACS) 2008 guidelines were 255 (76.6%), of whom 202 (79.2%) with an indication to an anti-HIV treatment, 30 (11.8%)without an indication, and 21 (8.2%) with cirrhosis. Among the 78 not-consistent patients, LAM mono-therapy (n = 60, 76.9%) was the most common regimen, 34 (56.7%) of them showing HBV DNA load below 1x10(3) IU/mL. Previous anti-HBV treatment (p = 0.01) and a triple HDV co-infection (p = 0.03) reduced the chance of not-consistent regimens. Conversely, HCV co-infection was independently associated with an increased odds ratio of being inconsistently treated (p = 0.004). CONCLUSION: Our study shows that Italian IDCs treat for HBV infection the vast majority of HIV/HBV co-infected patients with no disparities limiting access to antiviral therapy. In approximately two-thirds of the patients on treatment, anti-HBV regimens are consistent with 2008 EACS guidelines. Finally, our study identifies scenarios in which clinical practice deviates from recommendations, as in case of sub-optimal regimens with effective anti-HBV response.

Impact of previous ART and of ART initiation on outcome of HIV-associated tuberculosis.

BACKGROUND: Combination antiretroviral therapy (cART) has progressively decreased mortality of HIV-associated tuberculosis .To date, however, limited data on tuberculosis treatment outcomes among coinfected patients who are not ART-naive at the time of tuberculosis diagnosis are available. METHODS: A multicenter, observational study enrolled 246 HIV-infected patients diagnosed with tuberculosis, in 96 Italian infectious diseases hospital units, who started tuberculosis treatment. A polytomous logistic regression model was used to identify baseline factors associated with the outcome. A Poisson regression model was used to explain the effect of ART during tuberculosis treatment on mortality, as a time-varying covariate, adjusting for baseline characteristics. RESULTS: Outcomes of tuberculosis treatment were as follows: 130 (52.8%) were successfully treated, 36 (14.6%) patients died in a median time of 2 months (range: 0-16), and 80 (32.6%) had an unsuccessful outcome. Being foreign born or injecting drug users was associated with unsuccessful outcomes. In multivariable Poisson regression, cART during tuberculosis treatment decreased the risk of death, while this risk increased for those who were not ART-naive at tuberculosis diagnosis. CONCLUSIONS: ART during tuberculosis treatment is associated with a substantial reduction of death rate among HIV-infected patients. However, patients who are not ART-naive when they develop tuberculosis remain at elevated risk of death.

HIV incidence estimate combining HIV/AIDS surveillance, testing history information and HIV test to identify recent infections in Lazio, Italy.

BACKGROUND: The application of serological methods in HIV/AIDS routine surveillance systems to identify persons with recently acquired HIV infection has been proposed as a tool which may provide an accurate description of the current transmission patterns of HIV. Using the information about recent infection it is possible to estimate HIV incidence, according to the model proposed by Karon et al. in 2008, that accounts for the effect of testing practices on the number of persons detected as recently infected. METHODS: We used data from HIV/AIDS surveillance in the period 2004-2008 to identify newly diagnosed persons. These were classified with recent/non-recent infection on the basis of an avidity index result, or laboratory evidence of recently acquired infection (i.e., previous documented negative HIV test within 6 months; or presence of HIV RNA or p24 antigen with simultaneous negative/indeterminate HIV antibody test). Multiple imputation was used to impute missing information. The incidence estimate was obtained as the number of persons detected as recently infected divided by the estimated probability of detection. Estimates were stratified by calendar year, transmission category, gender and nationality. RESULTS: During the period considered 3,633 new HIV diagnoses were reported to the regional surveillance system. Applying the model, we estimated that in 2004-2008 there were 5,465 new infections (95%CI: 4,538-6,461); stratifying by transmission category, the estimated number of infections was 2,599 among heterosexual contacts, 2,208 among men-who-have-sex-with-men, and 763 among injecting-drug-users. In 2008 there were 952 (625-1,229) new HIV infections (incidence of 19.9 per 100,000 person-years). In 2008, for men-who-have-sex-with-men (691 per 100,000 person-years) and injecting drug users (577 per 100,000 person-years) the incidence remained comparatively high with respect to the general population, although a decreasing pattern during 2004-2008 was observed for injecting-drug-users. CONCLUSIONS: These estimates suggest that the transmission of HIV infection in Lazio remains frequent and men-who-have-sex-with men and injecting-drug-users are still greatly affected although the majority of new infections occurs among heterosexual individuals.

Determinants of access to experimental antiretroviral drugs in an Italian cohort of patients with HIV: a multilevel analysis.

BACKGROUND: Identification of the determinants of access to investigational drugs is important to promote equity and scientific validity in clinical research. We aimed to analyze factors associated with the use of experimental antiretrovirals in Italy. METHODS: We studied participants in the Italian Cohort of Antiretroviral-Naive Patients (ICoNA). All patients 18 years or older who had started cART (≥ 3 drugs including at least two NRTI) after their enrolment and during 1997-2007 were included in this analysis. We performed a random effect logistic regression analysis to take into account clustering observations within clinical units. The outcome variable was the use of an experimental antiretroviral, defined as an antiretroviral started before commercial availability, in any episode of therapy initiation/change. Use of an experimental antiretroviral obtained through a clinical trial or an expanded access program (EAP) was also analyzed separately. RESULTS: A total of 9,441 episodes of therapy initiation/change were analyzed in 3,752 patients. 392 episodes (360 patients) involved an experimental antiretroviral. In multivariable analysis, factors associated with the overall use of experimental antiretrovirals were: number of experienced drugs (≥ 8 drugs versus "naive": adjusted odds ratio [AOR] = 3.71) or failed antiretrovirals(3-4 drugs and ≥ 5 drugs versus 0-2 drugs: AOR = 1.42 and 2.38 respectively); calendar year (AOR = 0.80 per year) and plasma HIV-RNA copies/ml at therapy change (≥ 4 log versus < 2 log: AOR = 1.55). The probability of taking an experimental antiretroviral through a trial was significantly lower for patients suffering from liver co-morbidity(AOR = 0.65) and for those who experienced 3-4 drugs (vs naive) (AOR = 0.55), while it increased for multi-treated patients(AOR = 2.60). The probability to start an experimental antiretroviral trough an EAP progressively increased with the increasing number of experienced and of failed drugs and also increased for patients with liver co-morbidity (AOR = 1.44; p = 0.053). and for male homosexuals (vs heterosexuals: AOR = 1.67). Variability of the random effect associated to clinical units was statistically significant (p < 0.001) although no association was found with specific characteristics of clinical unit examined. CONCLUSIONS: Among patients with HIV infection in Italy, access to experimental antiretrovirals seems to be influenced mainly by exhaustion of treatment options and not by socio-demographic factors.

Liver protein profiling in chronic hepatitis C: identification of potential predictive markers for interferon therapy outcome.

The current anti-hepatitis C virus (HCV) therapy, based on pegylated-interferon alpha and ribavirin, has limited success rate and is accompanied by several side effects. The aim of this study was to identify protein profiles in pretreatment liver biopsies of HCV patients correlating with the outcome of antiviral therapy. Cytosolic or membrane/organelle-enriched protein extracts from liver biopsies of eight HCV patients were analyzed by two-dimensional fluorescence difference gel electrophoresis and mass spectrometry. Overall, this analysis identified 21 proteins whose expression levels correlate with therapy response. These factors are involved in interferon-mediated antiviral activity, stress response, and energy metabolism. Moreover, we found that post-translational modifications of dihydroxyacetone kinase were also associated with therapy outcome. Differential expression of the five best performing markers (STAT1, Mx1, DD4, DAK, and PD-ECGF) was confirmed by immunoblotting assays in an independent group of HCV patients. Finally, we showed that a prediction model based on the expression levels of these markers classifies responder and nonresponder patients with an accuracy of 85.7%. These results provide evidence that the analysis of pretreatment liver protein profiles is valuable for discriminating between responder and nonresponder HCV patients, and may contribute to reduce the number of nonresponder patients exposed to therapy-associated risks.

Standardization and performance evaluation of "modified" and "ultrasensitive" versions of the Abbott RealTime HIV-1 assay, adapted to quantify minimal residual viremia.

BACKGROUND: Numerous studies investigating clinical significance of HIV-1 minimal residual viremia (MRV) suggest potential utility of assays more sensitive than those routinely used to monitor viral suppression. However currently available methods, based on different technologies, show great variation in detection limit and input plasma volume, and generally suffer from lack of standardization. OBJECTIVES: In order to establish new tools suitable for routine quantification of minimal residual viremia in patients under virological suppression, some modifications were introduced into standard procedure of the Abbott RealTime HIV-1 assay leading to a "modified" and an "ultrasensitive" protocols. STUDY DESIGN: The following modifications were introduced: calibration curve extended towards low HIV-1 RNA concentration; 4 fold increased sample volume by concentrating starting material; reduced volume of internal control; adoption of "open-mode" software for quantification. Analytical performances were evaluated using the HIV-1 RNA Working Reagent 1 for NAT assays (NIBSC). Both tests were applied to clinical samples from virologically suppressed patients. RESULTS: The "modified" and the "ultrasensitive" configurations of the assay reached a limit of detection of 18.8 (95% CI: 11.1-51.0 cp/mL) and 4.8 cp/mL (95% CI: 2.6-9.1 cp/mL), respectively, with high precision and accuracy. In clinical samples from virologically suppressed patients, "modified" and "ultrasensitive" protocols allowed to detect and quantify HIV RNA in 12.7% and 46.6%, respectively, of samples resulted "not-detectable", and in 70.0% and 69.5%, respectively, of samples "detected <40 cp/mL" in the standard assay. CONCLUSIONS: The "modified" and "ultrasensitive" assays are precise and accurate, and easily adoptable in routine diagnostic laboratories for measuring MRV.

Accuracy of immunodiagnostic tests for active tuberculosis using single and combined results: a multicenter TBNET-Study.

BACKGROUND: The clinical application of IFN-gamma release assays (IGRAs) has recently improved the diagnosis of latent tuberculosis infection. In a multicenter study of the Tuberculosis Network European Trialsgroup (TBNET) we aimed to ascertain in routine clinical practice the accuracy of a novel assay using selected peptides encoded in the mycobacterial genomic region of difference (RD) 1 for the diagnosis of active tuberculosis in comparison with tuberculin skin test (TST), QuantiFERON-TB GOLD In-Tube (Cellestis Ltd., Carnegie, Australia) and T-SPOT.TB (Oxfordimmunotec, Abingdon, UK). PRINCIPAL FINDINGS: 425 individuals from 6 different European centres were prospectively enrolled. We found that sensitivity of the novel test, TST, QuantiFERON-TB GOLD In-Tube and T-SPOT.TB was respectively 73.1%, 85.3%, 78.1%, and 85.2%; specificity was respectively 70.6%, 48.0%, 61.9% and 44.3%; positive likelihood ratios were respectively 2.48, 1.64, 2.05, and 1.53; negative likelihood ratios were respectively 0.38, 0.31, 0.35, 0.33. Sensitivity of TST combined with the novel test, QuantiFERON-TB GOLD In-Tube and T-SPOT.TB increased up to 92.4%, 97.7% and 97.1%, respectively. The likelihood ratios of combined negative results of TST with, respectively, the novel test, QuantiFERON-TB GOLD In-Tube and T-SPOT.TB were 0.19, 0.07 and 0.10. CONCLUSIONS: The assay based on RD1 selected peptides has similar accuracy for active tuberculosis compared with TST and commercial IGRAs. Then, independently of the spectrum of antigens used in the assays to elicit mycobacterial specific immune responses, the novel test, IGRAs, and the TST do not allow an accurate identification of active tuberculosis in clinical practice. However, the combined use of the novel assay or commercial IGRAs with TST may allow exclusion of tuberculosis.

Late presenters in an HIV surveillance system in Italy during the period 1992-2006.

OBJECTIVES: The objectives of this study are to describe trends over time from 1992 to 2006 in the number of newly diagnosed HIV-infected individuals in Modena (Italy) and to describe their clinical and immunological characteristics. We also identify risk factors associated with presenting at late stages of HIV disease. METHODS: All new HIV diagnoses with at least 1 CD4 cell count and known stage of HIV disease were included. Using multivariate logistic regression models, we examined factors associated with being a late presenter, defined as individuals presenting with CD4 cell count <200 cells per microliter or AIDS within 3 months of their HIV-positive test. A quantile regression model was used to examine changes in CD4 cell count at presentation and trends over time. RESULTS: Of 844 newly diagnosed individuals included in analyses, 332 (39%) were late presenters, and this proportion remained constant over time (P = 0.106). Older age, male sex, and foreign born were the only determinants of being a late presenter. Persons newly diagnosed in 2002-2006 were less likely to present with an advanced clinical status. DISCUSSION: A substantial proportion of new HIV diagnoses are still at advanced stages of disease. In particular, foreign-born and heterosexual males still represent the largest part of AIDS presenters. Efforts are needed to encourage HIV testing and reduce the proportion who first seek HIV care at such a late stage.

[Kidney transplant and cancer risk: an epidemiological study in Northern and Central Italy]. / Trapianto di rene e rischio di cancro: studio epidemiologico in Nord e Centro Italia.

OBJECTIVE: This investigation aimed at highlighting the cancer risk of recipients of kidney transplant in northern and central Italy. METHODS: Data on 2,120 kidney transplant recipients from Niguarda Ca' Granda Hospital Milan, or from Policlinico "A. Gemelli", Rome, were analyzed The period at risk of developing cancer (person-years, PY) was computed from 30 days after transplant to date of cancer diagnosis, or date of death, or date of re-entering dialysis, or date of last follow-up. Observed and expected numbers of cancer were compared through sex- and age-standardized incidence ratios (SIRs) and 95% confidence intervals (CIs). The transplant attributable fraction (AF) of cancer cases and incidence rate ratios (IRR) were also computed. RESULTS: After 16.594 PY of follow-up (median flow-up: 6.8 years), 121 cancer cases were diagnosed (729.2 cases/10(5) PY). The SIR for all cancers was 1.9. Kaposi's sarcoma (KS) (27 cases observed, SIR = 82) and non-Hodgkins lymphoma (NHL) (18 cases observed a SIR = 6.4 were the most common cancers. Significantly increased SIRs were also noted for native kidney (11 cases observed SIR = 4.9), corpus uteri (6 cases observed SIR = 4.6), and liver (6 cases observed, SIR = 3.1). The transplant AF was 46.9%, largely due to KS (98.8%) and NHL (84.3%). Since SIRs decreased with increasing age, the transplant AF ranged from 73.2% below 45 years of age to 30.4% after 54. Among risk factors, area of birth strongly influenced the risk of KS, with a 3-fold higher risk in those born in the South of Italy as compared to those born in the northern part. CONCLUSIONS: Immune depression after kidney transplantation entails a two-fold increased overall risk of cancer, mainly related to cancers associated to a viral aetiology. Furthermore, our findings suggest the need to adopt a specific serological screening for the prevention of post-transplant KS in individuals born in southern Italy.

HIV coinfection and antiretroviral therapy enhances liver steatosis in patients with hepatitis C, but only in those infected by HCV genotype other than 3.

BACKGROUND: Liver steatosis is a common finding in hepatitis C virus (HCV) infection and is associated with an increased progression of the disease. However, HCV genotype 3 steatosis presents a peculiar and virus-induced pathogenesis. We analysed the effect of HIV coinfection and antiretroviral therapy on hepatic steatosis and the effect of the steatosis on fibrosis in patients with or without HCV genotype 3 infection. METHODS: All consecutive HIV-infected and uninfected patients who had undergone a liver biopsy for evaluation of HCV infection at the Infectious Diseases Clinic (Modena, Italy) were included in this study. Primary outcomes were the presence or absence of steatosis or the presence of moderate or advanced fibrosis. RESULTS: A total of 284 patients were enrolled: 187 infected by HCV and 97 coinfected with HIV and HCV. In HCV genotype 3 patients, only HCV-related variables, such as plasma HCV RNA levels (odds ratio [OR] per log10 1.68, P < 0.001) and estimated duration of HCV infection (OR per year 1.17, P = 0.004) were associated with steatosis. In patients infected with other HCV genotypes, steatosis was associated with older age (OR per 5 years 1.47, P < 0.001), with exposure to d-drugs in HIV-HCV-coinfected patients (OR 2.60, P = 0.04) and specifically exposure to stavudine (OR 2.76 HIV-HCV-coinfected versus not HIV-infected patients, P = 0.04). Steatosis was independently associated with bridging fibrosis only in patients infected by HCV genotype other than 3 (OR 4.03, P = 0.01). CONCLUSIONS: Hepatic steatosis, in both HCV-monoinfected and in HIV-HCV-coinfected patients, is strongly correlated with HCV genotype 3, probably through interactions between HCV virus and liver cells. HIV-related increase of steatosis in patients with HCV is probably related to antiretroviral drugs, especially stavudine, in patients infected by HCV genotype other than 3.