Is physician assessment of alcohol consumption useful in predicting risk of severe liver disease among people with HIV and HIV/HCV co-infection?

BACKGROUND: Alcohol consumption is a known risk factor for liver disease in HIV-infected populations. Therefore, knowledge of alcohol consumption behaviour and risk of disease progression associated with hazardous drinking are important in the overall management of HIV disease. We aimed at assessing the usefulness of routine data collected on alcohol consumption in predicting risk of severe liver disease (SLD) among people living with HIV (PLWHIV) with or without hepatitis C infection seen for routine clinical care in Italy. METHODS: We included PLWHIV from two observational cohorts in Italy (ICONA and HepaICONA). Alcohol consumption was assessed by physician interview and categorized according to the National Institute for Food and Nutrition Italian guidelines into four categories: abstainer; moderate; hazardous and unknown. SLD was defined as presence of FIB4 > 3.25 or a clinical diagnosis of liver disease or liver-related death. Cox regression analysis was used to evaluate the association between level of alcohol consumption at baseline and risk of SLD. RESULTS: Among 9542 included PLWHIV the distribution of alcohol consumption categories was: abstainers 3422 (36%), moderate drinkers 2279 (23%), hazardous drinkers 637 (7%) and unknown 3204 (34%). Compared to moderate drinkers, hazardous drinking was associated with higher risk of SLD (adjusted hazard ratio, aHR = 1.45; 95% CI: 1.03-2.03). After additionally controlling for mode of HIV transmission, HCV infection and smoking, the association was attenuated (aHR = 1.32; 95% CI: 0.94-1.85). There was no evidence that the association was stronger when restricting to the HIV/HCV co-infected population. CONCLUSIONS: Using a brief physician interview, we found evidence for an association between hazardous alcohol consumption and subsequent risk of SLD among PLWHIV, but this was not independent of HIV mode of transmission, HCV-infection and smoking. More efforts should be made to improve quality and validity of data on alcohol consumption in cohorts of HIV/HCV-infected individuals.

Incidence and predictors of single drug discontinuation according to the presence of HCV coinfection in HIV patients from the ICONA Foundation Cohort Study.

To evaluate incidence rates of and predictors for any antiretroviral (ART) drug discontinuation by HCV infection status in a large Italian cohort of HIV infected patients. All patients enrolled in ICONA who started combination antiretroviral therapy (cART) containing abacavir or tenofovir or emtricitabine or lamivudine plus efavirenz or rilpivirine or atazanavir/r or darunavir/r (DRV/r) or lopinavir/r or dolutegravir or elvitegravir or raltegravir were included. Multivariate Poisson regression models were used to determine factors independently associated with single ART drug discontinuation. Inverse probability weighting method to control for potential informative censoring was applied. Data from 10,637 patients were analyzed and 1,030 (9.7%) were HCV-Ab positive. Overall, there were 15,464 ART discontinuations due to any reason in 82,415.9 person-years of follow-up (PYFU) for an incidence rate (IR) of 18.8 (95% confidence interval [95%CI] 18.5-19.1) per 100 PYFU. No difference in IR of ART discontinuation due to any reason between HCV-infected and -uninfected patients was found. In a multivariable Poisson regression model, HCV-infected participants were at higher risk of darunavir/r discontinuation due to any reason (adjusted incidence rate ratio = 1.5, 95%CI 1.01-2.22, p value = 0.045) independently of demographics, HIV-related, ART and life-style factors. Among DRV/r treated patients, we found that HCV-viremic patients had twice the risk of ART discontinuation due to any reason than HCV-aviremic patients. In conclusion, HIV/HCV coinfected patients had a marginal risk increase of DRV/r discontinuation due to any reason compared with those without coinfection.

Proportion and factors associated with recent HIV infection in a cohort of patients seen for care in Italy over 1996-2014: Data from the ICONA Foundation Study cohort.

In Italy the prevalence of recent HIV infection (RHI) isn't currently monitored. Early diagnosis is crucial to allow introduction of antiretroviral therapy (cART) in the recent phase of infection. We aimed to estimate the proportion and the determinants of RHI among patients enrolled in the ICONA cohort; we explored differences in the median time from HIV diagnosis to cART initiation and in the viro-immunological response between RHI and Less Recent HIV infections (NRHI). We included antiretroviral-naïve HIV-positive patients enrolled in the cohort with documented dates of HIV-negative and positive antibodies tests, grouped in RHI (estimated date of seroconversion within 12 months of enrolment) and NRHI. Proportion of RHI and the trend of this proportion by calendar period (1996-2014) were investigated (Chi-square test). Logistic regression analysis was employed to identify factors associated with RHI. The time from seroconversion to cART initiation was compared in RHI and NRHI overall and after stratification by calendar period (survival analysis). We finally explored the time from starting cART to HIV-RNA <50 copies/mL and to CD4+ gain ≥200 cells/mmc by Cox regression. HIV seroconversion could be estimated for 2608/12,616 patients: 981/2608 (37.6%) were RHI. Proportion of RHI increased in recent calendar periods and was associated with younger age, baseline higher HIV-RNA and CD4+ count. There wasn't difference in the 2-year estimates of cART start between RHI and NRHI, regardless of calendar period. Rates and hazards of virological response were similar in RHI versus NRHI. RHI showed a 1.5-fold higher probability of CD4+ gain, also following adjustment for calendar period and cART regimen, and for age, HCV and smoking; the difference in probability was however attenuated after further controlling for baseline HIV-RNA and CD4+ T-cells. The increased proportion of RHI over time suggests that in recent years in Italy HIV infections are more likely to be detected earlier than before. The similar rates of cART introduction and viro-immunological response in RHI and NRHI probably reflect the efficacy of the modern cART regimens. An improvement of the prevention services is warranted to allow an early cART access, also in the perspective of therapy as prevention.

A retrospective study of viral central nervous system infections: relationship amongst aetiology, clinical course and outcome.

PURPOSE: To describe the clinical pattern of viral central nervous system (CNS) infections and compare meningitis and encephalitis. METHODS: This is a retrospective study reporting the clinical characteristics and outcome of 138 cases of viral meningitis and meningoencephalitis in a real life experience at a referral centre in Turin, Northern Italy. RESULTS: Enteroviruses were predominant in younger patients who were mainly presenting with signs of meningitis, had shorter hospital admission and absence of complications, whereas herpesviruses had more often signs of encephalitis, were more frequent in elderly patients, had longer hospital admission and frequent complications and sequelae. CONCLUSIONS: Two main clinical entities with different epidemiology, clinical aspects and prognosis may be identified within the group of viral CNS inefctions.

Switch of predicted HIV-1 tropism in treated subjects and its association with disease progression.

Dynamics of human immunodeficiency virus type 1 (HIV-1) tropism after antiretroviral therapy (ART) initiation and their association with disease progression are poorly investigated.This was a cohort study on subjects from the ICONA cohort receiving ART with persistently detectable (PD) or persistently undetectable (PU) viral load (VL) and with stored plasma or peripheral blood mononuclear cell (PBMC) samples at 2 time-points (T1, T2) after ART initiation. HIV-1 co-receptor tropism was determined by V3-loop sequencing and the geno2pheno algorithm. A switch in viral tropism was defined if the tropism classification at T2 differed from that observed at T1. Time to disease progression, defined as the occurrence of a new acquired immune deficiency syndrome (AIDS)-defining event/death from T2, was also evaluated.One hundred ninety-five patients were analyzed (124 PD, 71 PU). Over a median follow-up of 22.6 (19.8-28.1) months, PD and PU patients showed similar rates (95% confidence interval) of switch to a non-R5 virus [PD: 6.9 (3.7-11.2)/100-person-years of follow-up (PYFU); PU: 8.0 (3.4-14.5)/100-PYFU; P = 0.63] and of switch to a R5 virus [PD: 15.4 (7.3-26.4)/100-PYFU; PU: 8.1 (2.5-16.7)/100-PYFU; P = 0.38]. Switch to non-R5 virus was predicted by nadir CD4+ before T1.Twenty-two (18%) PD and 4 (6%) PU subjects experienced disease progression (P = 0.02). The risk of disease progression was independently associated with a switch in co-receptor tropism (adjusted hazard ratio = 4.06, 95% CI: 1.20-13.80, P = 0.03) as well as age, AIDS diagnosis, nadir CD4+ before T2, current CD4+, and VL.Switch of HIV-1 tropism under ART occurs in both directions, with similar rates in subjects with PD or PU VL and it might be predictive of future unfavorable clinical outcome.

High-density lipoprotein-cholesterol levels and risk of cancer in HIV-infected subjects: Data from the ICONA Foundation Cohort.

Investigation of the relationship between high-density lipoprotein-cholesterol (HDL-c) and the risk of developing cancer in a prospective cohort of human immunodeficiency virus (HIV)-infected patients.The Italian Cohort of Antiretroviral-naïve Patients Foundation Cohort is an Italian multicenter observational study recruiting HIV-positive patients while still antiretroviral treatment-naïve, regardless of the reason since 1997.Patients with at least 1 HDL-c value per year since enrollment and one such value before antiretroviral treatment initiation were included. HDL-c values were categorized as either low (<39 mg/dL in males or <49 mg/dL in females) or normal. Cancer diagnoses were classified as AIDS-defining malignancies (ADMs) or non-AIDS-defining malignancies (NADMs). Kaplan-Meier curves and Cox proportional-hazards regression models were used.Among 4897 patients (13,440 person-years of follow-up [PYFU]), 104 diagnoses of cancer were observed (56 ADMs, 48 NADMs) for an overall incidence rate of 7.7 (95% confidence interval [CI] 6.3-9.2) per 1000 PYFU.Low HDL-c values at enrollment were associated with higher risk both of cancer (crude hazard ratio [HR] 1.72, 95% CI 1.16-2.56, P = 0.007) and of NADM (crude HR 2.50, 95% CI 1.35-4.76, P = 0.003). Multivariate analysis showed that the risk of cancer diagnosis was higher in patients with low HDL-c values (adjusted HR [AHR] 1.87, 95% CI 1.18-2.95, P = 0.007) in older patients, those patients more recently enrolled, and in those with low current cluster of differentiation 4+ levels, and/or high current HIV-ribonucleic acid.The multivariate model confirmed an association between HDL-c (AHR 2.61, 95% CI 1.40-4.89, P = 0.003) and risk of NADM.Low HDL-c is an independent predictor of cancer in HIV-1-infected subjects.

Unmet Needs for a Rapid Diagnosis of Chikungunya Virus Infection.

Rapid Diagnosis of Chikungunya Virus Infection.

Louseborne Relapsing Fever among East African Refugees, Italy, 2015.

During June 9-September 30, 2015, five cases of louseborne relapsing fever were identified in Turin, Italy. All 5 cases were in young refugees from Somalia, 2 of whom had lived in Italy since 2011. Our report seems to confirm the possibility of local transmission of louse-borne relapsing fever.

Diagnostic and therapeutic appropriateness in bone and joint infections: results of a national survey.

The impact of infectious diseases (ID) specialist consultation in the management of many types of bacterial infections has been fully demonstrated but not for bone and joint infections (BJIs). Nineteen ID Italian centres collected of data from June 2009 to May 2012. Italian guidelines (2009) were used to determine the appropriateness of the diagnostic and therapeutic process of BJIs before and after consulting an ID specialist. Data on 311 patients were collected: 111 cases of prosthetic joint infection, 99 osteomyelitis, 64 spondylodiscitis and 37 fixation device infection. A significant increase of microbiological investigations, imaging techniques and blood inflammation markers were noted after consulting the ID specialist. Moreover, inappropriateness of treatment duration, dosage, and number of administrations significantly decreased after consultation. Infectious disease specialist intervention in the management of BJIs significantly increases the appropriateness both in performing instrumental and laboratory analysis, but especially in determining the correct therapy.

Evaluation of a Cognitive Rehabilitation Protocol in HIV Patients with Associated Neurocognitive Disorders: Efficacy and Stability Over Time.

The primary aim of the present study was to evaluate the efficacy and stability over time of a cognitive rehabilitation protocol (restorative and compensatory approach) in HIV/AIDS patients with HIV-associated Neurocognitive Disorder (HAND). At baseline, 32 HIV/AIDS patients (16 with and 16 without HAND) were assessed with a neuropsychological battery (i.e., pre-assessment) consisting of 22 tests covering eight cognitive domains. Then, the experimental group was administered over 4 months a cognitive rehabilitation protocol aimed at improving four cognitive domains by means of eight paper and pencil/computer-based exercises. The control group received guideline-adherent clinical care (i.e., standard of care). At the end of the cognitive treatment, both groups were re-administered the neuropsychological battery (i.e., post-assessment). Additionally, 6 months after post-assessment, the experimental group was given the same neuropsychological battery (i.e., follow up-assessment). In order to test the efficacy of the cognitive rehabilitation protocol, we compared between groups the results of the neuropsychological battery at the pre- and post-assessments. In order to evaluate the stability over time, the effects of the cognitive rehabilitation protocol was examined comparing within the experimental group the results of the neuropsychological battery at post- and follow up-assessments. Our results show that the two groups did not differ at the pre-assessment, but differed at post-assessment. Specifically, the experimental group showed a significant improvement in five domains (Learning and memory, Abstraction/executive functioning, Verbal fluency, Attention/working memory, and Functional), whereas the control group significantly worsened in the same domains. The improvement of the experimental group did not change in the follow up-assessment in two domains (Abstraction/executive functioning, Attention/working memory, and Functional). Overall, these findings support the efficacy and, to some extent, the stability over time of our cognitive rehabilitation protocol.

Travelers With Chikungunya Virus Infection Returning to Northwest Italy From the Caribbean and Central America During June-November 2014.

Chikungunya virus (CHIKV) has recently emerged in the Caribbean. In Italy, CHIKV vector is documented in the Po river valley; therefore, a risk for autochthonous outbreaks is present. We report a case series of seven imported CHIKV infections in travelers returning from the Caribbean and Latin America occurring between June and November 2014, in the area of Turin, Northwest Italy, 3 years after the last imported cases were reported. These cases are a reminder of the need to always consider CHIKV infection in travelers from these epidemic areas as well as the importance of a prompt diagnosis.

Increased risk of virological failure to the first antiretroviral regimen in HIV-infected migrants compared to natives: data from the ICONA cohort.

INTRODUCTION: Aim of the study was to evaluate possible disparities in access and/or risk of virological failure (VF) to the first antiretroviral (ART) regimen for migrants compared to Italian-born patients and to assess determinants of failure for the migrants living with HIV. METHODS: All native and migrant naïve patients enrolled in ICONA in 2004-2014 were included. Firstly, variables associated to ART initiation were analyzed. In a second analysis, the primary endpoint was time to failure after at least six months of ART, defined as: (a) VF (first of two consecutive viral load (VL) >50 and >200 copies/mL); (b) treatment discontinuation (TD) for any reason; and (c) treatment failure (TF: confirmed VL >200 cp/mL or TD). A Poisson multivariable analysis was performed to control for confounders. RESULTS: A total of 5777 HIV-pos ART-naïve patients (1179 migrants and 4598 natives) were evaluated. Most migrants were from sub-Saharan Africa (35.3%) and South-Central America/Caribbean (29%). Median duration of residency in Italy was five years (IQR 1-10). Baseline characteristics significantly differed between the two groups (Table 1); in particular, lower CD4 counts and higher frequency of AIDS events were observed in migrants vs natives. When adjusting for baseline confounders, migrants presented a lower chance to initiate ART compared to natives (OR 0.78, 95% CI 0.65-0.93, p=0.006). After ART initiation, the incidence rate of VF >50 cp/mL was 15.5 per 100 person-years (95% CI 12.8-18.8) in migrants and 8.9 in natives (95% CI 7.9-9.9), respectively. By multivariable analysis, migrants had a significantly higher risk of VF, both >50 cp/mL (OR 1.50, 95% CI 1.17-1.193, p=0.001) and >200 cp/mL (OR 1.59, 95% CI 1.23-2.05, p<0.001), and of TF (OR 1.15, 95% CI 1.00-1.32, p=0.045), while no differences were observed in TD risk. Among migrants, variables associated with a higher VF risk were age (for 10-year increase, OR 0.96, 95% CI 0.93-0.98, p=0.002), unemployment (OR 1.96, 95% CI 1.20-3.20, p=0.007) and use of a boosted PI based-regimen (OR 2.04, 95% CI 1.25-3.34, p=0.005 vs NNRTI-based), while pregnancy was associated with TD (OR 3.73, 95% CI 2.36-5.90, p<0.001) and TF (OR 3.13, 95% CI 02.00-4.89, p<0.001). CONCLUSIONS: Despite the use of more potent and safer antiretroviral drugs in the last 10 years, and even in a setting of universal access to ART, migrants living with HIV still present barriers to ART initiation and increased risk of VF compared to natives.

Combination of conventional blood cultures and the SeptiFast molecular test in patients with suspected sepsis for the identification of bloodstream pathogens.

We evaluated performances of the molecular test SeptiFast (SF) for the detection of agents of bloodstream infection (BSI) in patients with suspected sepsis, the majority of them under antibiotic treatment and at high prevalence of HIV-1 infection (10.5%). Matched SF and blood culture (BC) samples (n=1186) from 1024 patients were studied. Two hundred fifty-one episodes of BSI out of 1144 were identified with the combined methods (22%). SF identified more episodes of BSI than BC: 206 versus 176 (χ(2)=7.008, P=0.0081) and a significantly higher number of Gram-negative bacteria than BC (77 versus 53, χ(2)=9.12; P=0.0025), as well as of polymicrobial infections (χ(2)=4.50, P=0.0339). In conclusion, SF combined with BC improved the diagnosis of sepsis, especially in immunocompromised patients.

Timing of antiretroviral therapy initiation after a first AIDS-defining event: temporal changes in clinical attitudes in the ICONA cohort.

BACKGROUND: Time of starting antiretroviral therapy (ART) after diagnosis of specific AIDS-defining event (ADE) is a crucial aspect. Objectives of this study were to evaluate if in patients diagnosed with ADE the time to ART initiation may vary according to year of diagnosis and type of ADE. METHODS: All HIV+ persons diagnosed with an ADE over the 6 months prior to or after enrolment in the Icona Foundation study cohort and while ART-naive were grouped according to type of diagnosis: Those with ADE requiring medications interacting with ART [group A], those with ADE treatable only with ART [B] and other ADE [C]. Survival analysis by Kaplan-Meier was used to estimate the percentage of people starting ART, overall and after stratification for calendar period and ADE group. Multivariable Cox regression model was used to investigate association between calendar year of specific ADE and time to ART initiation. RESULTS: 720 persons with first ADE were observed over 1996-2013 (group A, n=171; B, n=115; C, n=434). By 30 days from diagnosis, 27% (95% CI: 22-32) of those diagnosed in 1996-2000 had started ART vs. 32% (95% CI: 24-40) in 2001-2008 and 43% (95% CI: 33-47) after 2008 (log-rank p=0.001). The proportion of patients starting ART by 30 days was 13% (95% CI 7-19), 40% (95% CI: 30-50) and 38% (95% CI 33-43) in ADE groups A, B and C (log-rank p=0.0001). After adjustment for potential confounders, people diagnosed after 2008 remained at increased probability of starting ART more promptly than those diagnosed in 1996-1999 (AHR 1.72 (95% CI 1.16-2.56). CONCLUSIONS: In our "real-life" setting, the time from ADE to ART initiation was significantly shorter in people diagnosed in more recent years, although perhaps less prompt than expected.

[The use of tolvaptan in a case of severe hyponatriemia in SIADH during meningitis]. / Utilizzo di tolvaptan in un caso di iponatriemia grave da SIADH.

Vaptans, vasopressin V2 receptor antagonists, are new drugs indicated in the treatment of Inappropriate ADH Secretion Syndrome (SIADH). We report a case of SIADH in a patient affected by AIDS. During a hospitalization for an ongoing CMV meningitis she developed a severe hyponatremia (114 mEq/L), which was initially treated with restriction of free water. When the diagnosis of SIADH was done (plasma Osmolarity 240 mOsm/kg, urinary sodium >30 mEq/24 h, normal volemia, lack of hypocorticosurrenalism and hypothyroidism), tolvaptan was given at the dose of 15 mg/day. Important fluctuations of plasma Na were observed thereafter (119-143 mEq/L). The progressive reduction of the drug (to 2 mg/die) allowed a stable correction of natremia. Unconsciousness determined the impossibility of the patient to freely access to water, thus explaining the fluctuations of natremia and the difficult management of the drug. Only a posology reduction to doses lower than those available for sale allowed a stable correction of natremia.

Role of serum free light chains in predicting HIV-associated non-Hodgkin lymphoma and Hodgkin's lymphoma and its correlation with antiretroviral therapy.

A nested case-control study was performed within the Italian cohort of naïve to antiretroviral human immunodeficiency virus (HIV) patients (ICONA) cohort to evaluate the role of serum free light chains (sFLC) in predicting non-Hodgkin's lymphoma (NHL) and Hodgkin lymphoma (HL) in HIV-infected individuals. Of 6513 participants, 86 patients developed lymphoma and 46 of these (NHL, 30; HL, 16) were included in this analysis having stored prediagnostic blood. A total of 46 serum case samples matched 1:1 to lymphoma-free serum control samples were assayed for κ and λ sFLC levels and compared by using conditional logistic regression. Because the polyclonal nature of free light chains (FLCs) was the focus of our study, we introduced the k + λ sum as the measurement of choice and as the primary variable studied. κ + λ sFLC values were significantly higher in patient with lymphoma than in controls, especially when considering samples stored 0-2-year period before the lymphoma diagnosis. In the multivariable analysis, the elevation of sFLC predicted the risk of lymphoma independently of CD4 count, (odd ratio of 16.85 for k + λ sFLC >2-fold upper normal limit (UNL) vs. normal value). A significant reduction in the risk of lymphoma (odd ratio of 0.07 in model with k + λ sFLC) was found in people with low sFLC and undetectable HIV viremia lasting more than 6 months. Our analysis indicates that an elevated polyclonal sFLC is a strong and sensitive predictor of the risk of developing lymphomas, and it is an easy to measure biomarker that merits consideration for introduction in routine clinical practice in people with HIV.

Malaria chemoprophylaxis recommendations for immigrants to Europe, visiting relatives and friends--a Delphi method study.

BACKGROUND: Numbers of travellers visiting friends and relatives (VFRs) from Europe to malaria endemic countries are increasing and include long-term and second generation immigrants, who represent the major burden of malaria cases imported back into Europe. Most recommendations for malaria chemoprophylaxis lack a solid evidence base, and often fail to address the cultural, social and economic needs of VFRs. METHODS: European travel medicine experts, who are members of TropNetEurop, completed a sequential series of questionnaires according to the Delphi method. This technique aims at evaluating and developing a consensus through repeated iterations of questionnaires. The questionnaires in this study included questions about professional experience with VFRs, controversial issues in malaria prophylaxis, and 16 scenarios exploring indications for prescribing and choice of chemoprophylaxis. RESULTS: The experience of participants was rather diverse as was their selection of chemoprophylaxis regimen. A significant consensus was observed in only seven of 16 scenarios. The analysis revealed a wide variation in prescribing choices with preferences grouped by region of practice and increased prescribing seen in Northern Europe compared to Central Europe. CONCLUSIONS: Improving the evidence base on efficacy, adherence to chemoprophylaxis and risk of malaria and encouraging discussion among experts, using techniques such as the Delphi method, may reduce the variability in prescription in European travel clinics.