Suchergebnisse

IntroductionThis study compares the trends of HIV inpatient admissions between a London tertiary HIV centre (United Kingdom) and four infectious disease wards in Italy (IT) to recognize common patterns across Europe.MethodsData regarding HIV inpatient admissions was collected by using discharge diagnostic codes from 1 January to 31 December 2012, including patient demographics, combined antiretroviral therapy (cART) history, CD4, viral load (VL) and mortality rates. Discharge diagnoses were categorized according to the International Classification of Disease (ICD) 9 and 10 system. All ICD categories that reach a 3% threshold of total admissions were analyzed.ResultsA total of 731 admissions (257 in Italy and 474 in the United Kingdom) for 521 patients (1.5 mean admission per patient). Female admissions were higher in Italy at 22.6% (n=58) compared to 14.9% (n=47) in the United Kingdom. Median age of patients was 47 years old. There was an undetectable VL in 65.8% (n=169) of admissions in Italy and 67.1% (n=319) in the United Kingdom (p=0.385); 86.4% (n=222) and 82.4% (n=389) of admissions were on cART, respectively. Mean CD4 was 302 in Italy compared to 368 in the United Kingdom (p=0.003). Average length of admission was 16 days with a 10.2% (n=21) mortality rate in Italy compared to 8 days with 2.8% (n=9) mortality in the United Kingdom (p<0.001). HCV co‐infection was present in 64.6% (n=166) in Italy and 13.5% (n=64) in the United Kingdom and commonest mode of transmission was needle use in Italy (67.3%, n=173) and men who have sex with men in the UK cohort (59.9%, n=284). The cause of inpatient admissions according to ICD codes can be seen in following Figure 1.ConclusionsSignificant differences in the duration of inpatient admission and mortality rates can be observed between these two cohorts which is secondary to the impact of Hepatitis C co‐infection in Italy. However increases in the number of Hepatitis C co‐infection patients amongst MSM in London has been reported [1] and route of transmission in Italy is shifting towards MSM [2], therefore it is important to learn how HIV is developing and managed in a global context to help plan future for services. The UK cohort demonstrates a wider range of conditions necessitating admission, and with an ageing HIV population, this is expected to increase in the future, requiring general and specialist HIV physicians to work closely together. The HIV‐RNA threshold is 400 copies/mL to account for blips according to British HIV Association (BHIVA) Guidelines 2012 [3].

BackgroundWe assessed the virological response of DRV/r‐based dual therapy in drug‐experienced patients included in the Italian antiretroviral resistance database (ARCA).Materials and MethodsPatients included in the study were treated with DRV/r in association with raltegravir (RAL), etravirine (ETV) or maraviroc (MAR) following treatment failure(s) and with a resistance test and at least one follow‐up visit available. Observation was censored at last visit under dual therapy and survival analysis and proportional hazard models were used, taking virological failure (confirmed >50 c/mL HIV‐RNA) as the end‐point.ResultsOf the total 221 patients included, 149 (67.4%) started DRV/r with RAL, 45 (20.4%) with ETV, 27 (12.2%) with MAR. Patients characteristics at the start of dual regimen were as follows: mean number of previous regimens, nine (IQR: 5–13); non‐B subtype, 17 (7.7%); median CD4 count, 347 (IQR: 246–544); undetectable viral load, 74 (33.5%). Full DRV/r resistance was detected in one (0.5%, HIV‐DB interpretation system), 13 (5.9%, ANRS) and 17 patients (7.7%, Rega). 69 virological failures (31.2%) were observed during follow‐up. At survival analysis, the overall proportion of failure was 29.2% at one year and 33.8% at two years. The proportion of failure was lower in patients starting with undetectable versus detectable viral load (13.3% and 25.2% versus 37.4% and 38.8% at one and two years, respectively, p=0.001 for both analyses) and in patients treated with DRV 600 BID versus 800 QD (HR: 0, 56; 95% CI 0.31–0.99; p<0.05). By regimen, patients treated with DRV/r‐RAL showed a non‐significant lower proportion of failure (27.7% at one year, 32.0% at two years) if compared with DRV/r‐MAR (35.9%, 47.1%) and DRV/r‐ETV (34.1%, 34.1% at one and two years). In the adjusted proportional model, no significant difference among the three regimens was detected. A significant lower risk of failure was associated with higher overall GSS (HIV‐DB HR: 0.53, 95% CI 0.32–0.88, p=0.014; Rega 0.60, 0.40‐0.88, p<0.01; ANRS 0.55, 0.34–0.90, p=0.017), while a higher risk of failure was associated with detectable HIV‐RNA (3.02, 1.70–5.72, p<0.001).ConclusionsAmong experienced patients, the best candidates to dual‐therapy regimens including DRV/r are those with undetectable viral load and higher GSS. The association with RAL is the most commonly used but no clear advantage with respect to ETV or MAR was observed in our dataset, possibly due to the limited sample size.

IntroductionThe introduction of combined antiretroviral treatment (cART) has reduced HIV‐associated morbidity and mortality, and changed the patients' perspective of life. As a result, Health Related Quality of Life (HRQOL) has become a crucial clinical issue.ObjectiveAssessment of HRQOL in a sample of Italian patients from IANUA study. Investigate correlation between CD4 cell counts, viral load and changes in HRQOL.Materials and MethodsEQ‐5D‐3L self‐reported questionnaire has been used in the evaluation of HRQOL. It assesses five dimensions: "mobility," "self care," "usual activities," "pain/discomfort" and "anxiety/depression." Each dimension has three levels: no problems, some problems and extreme problems. In addition, it includes a Visual Analogue Scale (VAS) where one's own health "today" is rated from 0 "worst imaginable health" to 100 "best imaginable health." The respondents provide information on marital status, education, employment/unemployment, other treatments used in addition to HAART (1,2,3,4,5 or more) and number of hospitalizations due to HIV/AIDS.Results684 patients completed the questionnaire: 231 females and 453 males. The mean age of the sample was 51 years (range 21–78). The mean VAS score was 69.9. 558 patients (81.5%) reported no problems in mobility. 642 patients (93.5%) had no problems in self care. 423 patients (61.8%) had no pain/discomfort while 219 had some problems. 326 patients (46.1%) had some problems in anxiety/depression.ConclusionsThe analysis of self‐reported questionnaires indicates that HRQOL in our sample group is not deeply affected by HIV/AIDS. The dimensions that are affected in the least are "mobility" and "self care" while the major problem is "anxiety/depression" with half of the sample reporting moderate or high level.

IntroductionThe 48‐week interim analysis of the MODAT study showed that confirmed virologic failure (CVF) was more frequent in patients simplifying to ATV/r monotherapy compared to maintaining ATV/r‐based triple therapy. The DSMB recommended stopping study enrollment but continuing follow‐up of enrolled patients. We present the 96‐week efficacy analysis.Material and MethodsMulticentre, randomized, open‐label, non‐inferiority trial (non‐inferiority margin −10%). Treatment failure (TF) was defined as CVF (two consecutive HIV‐RNA >50 cp/mL) or discontinuation for any cause. In the monotherapy arm, patients with CVF re‐introduced their previous NRTIs and remained in the study if HIV‐RNA <50 copies/mL within 12 weeks of re‐intensification.Results101 patients evaluated (Figure 1): 85% males, 21% HCV‐positive, median (IQR) age of 42 (36–48) years, baseline CD4+ 576 (447–743) cells/µL. In the 96‐week analysis (ITT; TF=failure), efficacy was 64% (32/50) in the monotherapy arm and 63% (32/51) in the triple‐therapy arm (difference +1.3%, 95% CI −17.5–20.1). Fourteen patients in monotherapy and two in triple‐therapy arm had CVF; median HIV‐RNA was 136 (72–376) copies/mL. In monotherapy arm, no PI or NRTI associated resistance mutations were observed at CVF. All patients who re‐intensified re‐suppressed. In monotherapy arm, TF was more frequent in HCV‐co‐infected patients (64% vs 28%; p=0.041). In the secondary analysis (ITT; re‐intensification=success), 82% (41/50) in monotherapy arm and 63% (32/51) in triple‐therapy arm were on study at week 96 (difference +19.3%, 95% CI 2.2–36.3). SAEs occurred in four (8%) patients in the monotherapy arm (one left basal pneumonia, one acute coronary stenosis, one traumatic lesion, one nephrolithiasis) and two (4%) in the triple therapy arm (one sepsis, one renal failure). Drug‐related adverse events (AEs) leading to discontinuation were three (6%) in the monotherapy arm (two AEs occurred in patients after successful re‐intensification) and 12 (23.5%) in the triple‐therapy (p=0.023).ConclusionsDespite the small sample size, the primary 96‐week analysis showed that simplification to ATV/r monotherapy showed inferior efficacy to maintaining ATV/r triple‐therapy but appeared to be superior when re‐intensification was considered success.

IntroductionSerious non‐AIDS events (SNAE) are frequent in HIV patients receiving cART. Current CD4 count was shown to be more strongly associated with infective compared to not‐infective SNAE and unable to predict cardiovascular events. We investigated the relationship between baseline and current CD4 count and the risk of both infective and non‐infective SNAE in HIV‐positive patients according to current ART use.MethodsWe included all HIV‐positive persons enrolled in the ICONA Foundation Study cohort who had at least one follow‐up visit. SNAE were grouped in infective (pneumonia, sepsis, endocarditis and meningitis) and non‐infective (malignancies, chronic kidney disease, cardiovascular events, hepatic events and pancreatitis) aetiology. Incidence of these event groups were calculated overall and according to baseline and current CD4 count (grouped as 0–200, 201–350, 351–500, 501–750, and >750 cells/mm3). Participants' follow‐up accrued from the date of enrolment (baseline) to a diagnosis of SNAE or their last visit. An event was defined the first time one of the considered SNAE occurred so that each person contributed a single event. A Poisson regression model for each of the two endpoints was used.ResultsA total of 10,822 patients were included (25.3% females, 38.2% heterosexuals) and 26.6% had hepatitis co‐infections. Median age was 36 (IQR 31–42) years. Overall, 423 not‐infective and 385 infective SNAE were included. The most frequent non‐infective SNAE were malignancies (n=202) and the most frequent infective SNAE were pneumonia (n=289). Crude rates of non‐infective SNAE were 0.78, 1.08 and 0.80/100 PYFU, and those of infective SNAE were 1.00, 0.51 and 0.66/100 PYFU in ART naive, currently off and currently on ART patients, respectively. Higher current CD4 count was associated with reduced risk of both infective and non‐infective SNAE in naives and in patients on ART (Table 1). The association was less strong in the group which suspended ART (for non‐infective SNAE the p value for interaction between current log‐CD4 and ART‐status, p=0.004). Conversely, we found no association between baseline CD4 count and risk of non‐infective SNAE in people treated with ART (p value for interaction = 0.0001). When CVD were considered separately, there was no association with CD4 count (not shown).ConclusionsOur findings show that, differently from ART naive, in ART‐treated patients, non‐infective SNAE are predicted by current but not by baseline CD4, suggesting that immune restoration is crucial to prevent these events.

IntroductionThe aim of this study was to analyze the likelihood and the predictors of discontinuation of first‐line regimen in the late HAART era.MethodologyAn observational multi‐center analysis of HIV‐positive patients enrolled in ICONA. Patients eligible were those starting a first‐line HAART after 1 January 2008. Discontinuation was defined as stop and/or switch of at least one drug of the regimen. All causes of discontinuation, as reported by the treating physician, were evaluated and cumulative risk of stopping was investigated according to age, gender, co‐morbidity, years since starting HAART, immuno‐virological status, third drug and backbone of the first regimen. Kaplan Meier (KM) analysis and Cox proportional hazards model were used for the outcome discontinuation of ≥1 drug regardless of the reason. For the KM estimates a competing risk approach was used to estimate the contribution of each of the reasons over time to the cumulative risk of stopping over time.ResultsData of 1759 patients who started first HAART and had at least one month of clinical follow‐up were analyzed. The overall discontinuation risk was 33% over a median follow‐up of 12 months. The likelihood of discontinuation by KM was 27% by one year (95% CI 25–29) and 41% by two years (95% CI 38–44). Main reason for stopping at least one drug in regimen was simplification (10%), followed by intolerance (7%), toxicity (5%), failure (2%) and other causes (8%). Estimates of the cumulative risk of discontinuation of ≥1 drug over time and according to reason are shown in Figure 1. In a multivariable Cox model independent predictors of discontinuation regardless of the reason were: longer time from HIV diagnosis to date of starting HAART (hazard ratio [HR] 0.96; 95% CI 0.93–1.00; p=0.039), regimens containing ZDV/3TC (HR 2.86; 95% CI 1.42–5.76; p=0.003 vs TDF/FTC) and an NNRTI‐based regimen (HR 2.47; 95% CI 0.91–6.72; p=0.07 vs regimens not NNRTI‐based).ConclusionsIn a previously reported analysis of the ICONA data [1], the overall risk of discontinuation of first‐line HAART was 36% with 21% due to intolerance/toxicity. In this updated analysis, the main reason for stopping is simplification (accounting for 32% of stops), reflecting the recent changes in recommendations aimed to minimize drug toxicity, enhancing adherence and quality of life.

IntroductionWe aimed at evaluating the efficacy and durability of a lopinavir/ritonavir‐based dual regimen (LPV/r‐DR) in virologically controlled HIV‐infected individuals in current clinical practice.MethodsPatients who have initiated for the first time a LPV/r‐DR with HIV‐RNA<50 copies/mL were included in this observational study. The main endpoints were: time to virological rebound [VR=time of first of two consecutive viral loads (VL)>50 copies/mL] and time to experience either a single VL>200 copies/mL or discontinuation/intensification (= treatment failure, TF). Individuals' follow‐up accrued from the date of starting the LPV/r‐DR to event or last available VL. Kaplan‐Meier curves and Cox regression analysis were used. Covariates included in the multivariable analysis were gender, age, route of transmission, hepatitis co‐infection, calendar year of starting the DR, nadir CD4+ count, VL at initiation of first cART, previous failures to protease inhibitors (PIs), time with undetectable VL before starting the DR and the type of DR [nucleoside reverse transcriptase (NRTI), non‐NRTI (NNRTI), raltegravir or maraviroc, with NRTI as reference group]. Results are presented as median (Q1, Q3) or frequency (%) as appropriate.Results108 individuals followed for 18 (7, 30) months were included; baseline (BL) characteristics are detailed in Table 1.LPV/r was associated with a NRTI in 51, with a NNRTI in 10, with raltegravir in 29, and with maraviroc in 18 individuals. By 36 months from switching to the LPV/r‐DR, the proportion of individuals with VR and TF was 10% (95% CI 3–17%) and 36% (95% CI 22–50%), respectively. We did not find any factor independently associated with the risk of VR. Older age (ARH=0.49 (95% CI 0.30–0.78) per 10 years older; p=0.003) was found to be protective from TF. Mean (SE) CD4+ cells/µL increase from BL to month 36 resulted significant: 195 (40.1) cells/µL (p=0.0028). We did not observe significant changes in AST, ALT, eGFR (MDRD formula), triglycerides and both total and HDL‐cholesterol.ConclusionsA LPV/r‐DR can be considered a valuable option in patients with HIV‐RNA<50 copies/mL and ongoing toxicity from the third drug of the regimen, although up to 17% of patients showed viral rebound by 3 years. Older patients are at lower risk of failure with this strategy, but larger sample size is needed to identify who might benefit from this strategy instead of others.

Action on social determinants is a main component of the World Health Organization End Tuberculosis (TB) Strategy. The aim of the study was to collect information on socioeconomic characteristics and biomedical risk factors in migrant TB patients in Italy and compare it with data collected among Italian TB patients. A cross-sectional study was conducted among TB patients aged ≥18 years over a 12-months enrolment period in 12 major Italian hospitals. Information on education, employment, housing and income was collected, and European Union Statistics on Income and Living Conditions index was used to assess material deprivation. Among migrants, we also analyzed factors associated with severe material deprivation. Migrants were compared with younger (18-64 years) and older (65+ years) Italians patients. Out of 755 patients enrolled (with a median age of 42 years, interquartile range: 31-53), 65% were migrants. Pulmonary, microbiologically confirmed, and new cases were 80%, 73%, and 87% respectively. Prevalence of co-morbidities (i.e. diabetes, chronic kidney disease, neoplastic diseases and use of immunosuppressive drugs) was lower among migrants compared to Italian TB patients, while indicators of socioeconomic status, income and housing conditions were worst in migrants. Forty-six percent of migrants were severely deprived vs. 9% of Italians (p<0.0001, 11.3% and 5.5% among younger and older Italians, respectively). Among migrants, being male, older, irregular, unemployed, with a shorter time spent in Italy, a lower education level, and without a co-morbidity diagnosis were factors associated with severe material deprivation at multi-variable logistic regression. Moreover, socioeconomic indicators for Italian patients did not differ from those reported for the general Italian population, while migrant TB patients seem to have a higher prevalence of severe material deprivation than other migrants residing in Italy. Intervention to address the needs of this population are urgent.

IntroductionThe persistence of immune activation and inflammation in HIV patients with HIV‐RNA (VL) undetectable causes many co‐morbidities [1–3]. The aim of this study is to correlate monocytes (m) and NK cell activation levels, soluble markers and oxidative stress with clinical, biochemical and metabolic data in HIV‐1 infected patients with VL≤50 copies (cp)/mL on antiretroviral therapy.Materials and MethodsMulticentre, cross‐sectional study in patients with VL≤50 cp/mL and on antiretroviral therapy by at least six months. We studied: activation/homing markers (CD38, HLA‐DR, CCR‐2, PDL‐1) on inflammatory, intermediate, proinflammatory m; activatory receptors NKp30, NKp46 and HLA‐DR on NK cells; soluble inflammatory (sCD14, adiponectina, MCP‐1) and stress oxidative markers (dRoms, antiRoms). Univariate analyses are performed with non‐parametric and Pearson tests. The significant correlations were adjusted for possible known confounding factors (smoking, Cytomegalovirus IgG serology, Raltegravir, Protease Inhibitor [PI] therapy and HCV‐RNA) with multivariate analysis.ResultsIn the 68 patients the positive correlation between age and antiRoms was significant also after adjustment for PI use (p=0.05). The% CD8+T was associated with% proinflammatory m (p=0.043) and with their expression of CCR2 mean fluorescence intensity (MFI) (p=0.012). The% NKp46+ was positively correlated with CD4+T count (p=0.001). The fibrinogen was positively associated with dRoms (p=0.052) and the positive correlation between triglycerides and antiRoms has been confirmed (p<0.001); the impact of antiRoms on HDL/triglycerides ratio (p=0.006) was observed after adjustment for PI use. The BMI was associated with smoking (p=0.011). Only the maraviroc‐treated patients showed minimal arterial pressure, fibrinogen and antiRoms lower (p=0.001, 0.004 e 0.006) and sCD14 values higher (p=0.029).ConclusionsPatients with long history of HIV infection and stable immunological and virological status showed interactions between acquired and innate immunity activation; moreover, the levels of some metabolic and inflammatory parameters correlate with oxidative stress values and innate immunity activation. The age, BMI and smoking impact metabolic and immunological parameters. The correlations between antiretroviral drugs and clinical‐immunological parameters need further confirmations.