Microbial translocation in chronic liver diseases.

The intestinal microflora is not only involved in the digestion of nutrients, but also in local immunity, forming a barrier against pathogenic microorganisms. The derangement of the gut microflora may lead to microbial translocation, defined as the passage of viable microorganisms or bacterial products (i.e., LPS, lipopeptides) from the intestinal lumen to the mesenteric lymph nodes and other extraintestinal sites. The most recent evidence suggests that microbial translocation (MT) may occur not only in cirrhosis, but also in the early stage of several liver diseases, including alcoholic hepatopathy and nonalcoholic fatty liver disease. Different mechanisms, such as small intestinal bacterial overgrowth, increased permeability of intestinal mucosa, and impaired immunity, may favor MT. Furthermore, MT has been implicated in the pathogenesis of the complications of cirrhosis, which are a significant cause of morbidity and mortality in cirrhotic subjects. Therapeutic strategies aiming at modulating the gut microflora and reducing MT have focused on antibiotic-based options, such as selective intestinal decontamination, and nonantibiotic-based options, such as prokinetics and probiotics. In particular, probiotics may represent an attractive strategy, even though the promising results of experimental models and limited clinical studies need to be confirmed in larger randomized trials

HAART in HIV+ naive elderly patients: immuno-virological response and clinical outcome

Purpose of the study Elderly patients (≥50 years) are increasing in the HIV population; HAART-related prolonged survival and late diagnosis of new HIV infections are possible reasons of this findings. It is debated whether older patients have a different response to HAART. The aim of this retrospective study was to evaluate efficacy of HAART and clinical outcome in a group of patients ≥50 year in comparison to a control group (<50 years-old)

Time trend in hypertension prevalence, awareness, treatment, and control in a contemporary cohort of HIV-infected patients: the HIV and Hypertension Study

Hypertension control is often inadequate in HIV patients. In a contemporary, nationwide cohort of Italian HIV-infected adults, we assessed time trends in hypertension prevalence, awareness, treatment, and control. We also evaluated predictors of cardiovascular events and of new-onset hypertension

Efficacy of 1998 <i>vs</i> 2006 first-line antiretroviral regimens for HIV infection: an ordinary clinics retrospective investigation

Purpose: The evidence suggesting increased HAART efficacy over time comes from randomized trials or cohort studies. This retrospective multicenter survey aimed to assess the variation over time in the efficacy and tolerability of first-line HAART regimens in unselected patients treated in ordinary clinical settings. Methods: Retrospective analysis of data of all patients starting first-line HAART regimens in 1998 and 2006 at adhering centers in the Italian CISAI group. Results: For the 543 patients included, mean age was 39.1 ± 9.8y in 1998 and 41.0 ± 10.7y in 2006 (p=0.03), with a similar proportion of males. Baseline mean log10 HIV-RNA was 4.56 ± 0.97 copies/mL in 1998 vs 4.91 ± 0.96 copies/mL in 2006 (p&lt;0.001); baseline mean CD4 T-cell counts were 343 ± 314/mm3 in 1998 vs 244 ± 174/mm3 in 2006 (p&lt;0.001). The following outcomes were significantly improved at 48w in 2006: proportion with undetectable HIV-RNA (86.3% vs 58.0%; p&lt;0.001); mean increase in CD4 T-cells count (252 ± 225 vs 173 ± 246; p&lt;0.001); HAART modification (20.1% vs 29.2%; p=0.02); HAART interruption (7.3% vs 14.6%; p=0.01); proportion reporting optimal adherence (92.2% vs 82.7%, p=0.03). No differences were observed in the prevalence of grade 3-4 WHO toxicities (26.4% vs 26.6%; p=0.9). Multivariate logistic regression showed that being treated in 1998 remained an independent predictor of virological failure after several adjustments, including adherence. Conclusions: Our data from patients not included in clinical trials or cohort studies provide an additional line of evidence that the effectiveness of HAART significantly improved in 2006. Treated patients, however, were significantly older and more frequently late HIV presenters in 2006 than in 1998.</br

"Diagnosis on the Dock" project: A proactive screening program for diagnosing pulmonary tuberculosis in disembarking refugees and new SEI model.

Abstract Objective From 2011 to 2017, the total number of refugees arriving in Europe, particularly in Italy, climbed dramatically. Our aim was to diagnose pulmonary TB in migrants coming from the African coast using a clinical-based port of arrival (PoA) screening program. Methods From 2016 to 2018, migrants coming via the Mediterranean Route were screened for body temperature and the presence of cough directly on the dock: if they were feverish with productive cough, their sputum was examined with NAAT; with a dry cough, they underwent Chest-X-ray (CXR). Those migrants with positive NAAT or CXR suggestive for TB were admitted to our ward. In addition, we plotted an SEI simulation of our project to evaluate the epidemiological impact of our screening. Results Out of 33.676 disembarking migrants, 314 (0.9%) had fever and cough: 80 (25.47%) with productive cough underwent NAAT in sputum, and 16 were positive for TB; 234 (74.52%) with dry cough had a CXR examination, and 39 were suggestive of TB, later confirmed by mycobacterial culture. The SEI-new model analysis demonstrated that our screening program significantly reduced TB spreading all over the country. Conclusions For possible future high migrant flows, PoA screening for TB has to be considered feasible and effective in decreasing TB spreading

Reversibility of Central Nervous System Adverse Events in Course of Art

The purpose of this study is to evaluate the frequency of central nervous system adverse events (CNS-AE) on dolutegravir (DTG) and non-DTG containing ART, and their reversibility, in the observational prospective SCOLTA cohort. Factors associated with CNS-AE were estimated using a Cox proportional-hazards model. 4939 people living with HIV (PLWH) were enrolled in DTG (n = 1179) and non-DTG (n = 3760) cohorts. Sixty-six SNC-AE leading to ART discontinuation were reported, 39/1179 (3.3%) in DTG and 27/3760 (0.7%) in non-DTG cohort. PLWH naive to ART, with higher CD4 + T count and with psychiatric disorders were more likely to develop a CNS-AE. The risk was lower in non-DTG than DTG-cohort (aHR 0.33, 95% CI 0.19-0.55, p &lt; 0.0001). One-year follow-up was available for 63/66 PLWH with CNS-AE. AE resolution was reported in 35/39 and 23/24 cases in DTG and non-DTG cohorts, respectively. The probability of AE reversibility was not different based on ART class, sex, ethnicity, CDC stage, or baseline psychiatric disorder. At the same time, a lower rate of event resolution was found in PLWH older than 50 years (p = 0.017). In conclusion, CNS-AE leading to ART discontinuation was more frequent in DTG than non-DTG treated PLWH. Most CNS-AE resolved after ART switch, similarly in both DTG and non-DTG cohorts

Elderly HIV-positive women: A gender-based analysis from the Multicenter Italian \u201cGEPPO\u201d Cohort

BACKGROUND: HIV-positive patients are facing age-and disease-related comorbidities. Since gender differences in viro-immunological, clinical and therapeutic features have been described, aim of this analysis was to explore such differences in elderly HIV-positive females compared to males coming from the same cohort. DESIGN: Cross-sectional study. SETTING: Ten Infectious Diseases Center participating to a new multicenter Italian geriatric Cohort aiming at describing health transition over time in HIV-positive individuals. PARTICIPANTS: HIV-positive patients aged 6565 years old. MEASUREMENTS: We recorded clinical, viro-immunological and therapeutical data. RESULTS: We included 210 women (17%) out of 1237 patients. Compared to males, elderly females were less likely to present a HIV-RNA &lt;50 copies/mL (74.3% vs. 81.8%, OR 0.64, 95%CI 0.44-0.93); they showed higher CD4+/CD8+ ratio (p = 0.016). Combined antiretroviral therapy (cART) strategies were similar between genders (p&gt;0.05), although women were less likely to be treated with protease Inhibitors (PIs) (p = 0.05); specifically, in triple-drug regimens females received less PIs (28% vs 38% p = 0.022) and more integrase inhibitors (30% vs. 20% p = 0.012). Bone disease was more common in females (p&lt;0.001) while males presented more frequently cardiovascular disease (CVD) (p&lt;0.001). In females with bone disease, PIs and boosted regimens (38% vs. 53.7% p = 0.026 and 30.4 vs 44.0% p = 0.048 respectively) were prescribed less frequently. Polypharmacy was common and similar in both genders (20% vs. 22.8%, p = &gt;0.05). A higher use of lipid-lowering drugs (20.5% vs. 14.8%, p = 0.04) was observed in females and yet they were less likely to receive anti-thrombotic agents (18.6% vs. 26.3%, p = 0.019) even when CVD was recorded (57.1% vs. 83.1%, p = 0.018). In multivariate analysis, we found that female gender was independently associated with a higher CD4+/CD8+ ratio but not with virological suppression. CONCLUSIONS: Elderly HIV-positive women display a worse virologic response despite a better immune reconstitution compared to males. The burden of comorbidities as well as the medications received (including cART) may slightly differ according to gender. Our data suggest that more efforts and focused interventions are needed in this population

Enhanced immunological recovery with early start of antiretroviral therapy during acute or early HIV infection–results of Italian Network of ACuTe HIV InfectiON (INACTION) retrospective study

ABSTRACT Background: Viral load peak and immune activation occur shortly after exposure during acute or early HIV infection (AEHI). We aimed to define the benefit of early start of antiretroviral treatment (ART) during AEHI in terms of immunological recovery, virological suppression, and treatment discontinuation. Setting: Patients diagnosed with AEHI (Fiebig stages I-V) during 2008-2014 from an analysis of 20 Italian centers. Methods: This was an observational, retrospective, and multicenter study. We investigated the ef- fect of early ART (defined as initiation within 3 months from AEHI diagnosis) on time to virolog- ical suppression, optimal immunological recovery (defined as CD4 count ≥ 500/μL, CD4 ≥ 30%, and CD4/CD8 ≥ 1), and first-line ART regimen discontinuation by Cox regression analysis. Results: There were 321 patients with AEHI included in the study (82.9% in Fiebig stage III-V). At diagnosis, the median viral load was 5.67 log10 copies/mL and the median CD4 count was 456 cells/μL. Overall, 70.6% of patients started early ART (median time from HIV diagnosis to ART initiation 12 days, IQR 6-27). Higher baseline viral load and AEHI diagnosis during 2012-2014 were independently associated with early ART. HBV co-infection, baseline CD4/CD8 ≥ 1, lower baseline HIV-RNA, and AEHI diagnosis in recent years (2012-2014) were independently associ- ated with a shorter time to virological suppression. Early ART emerged as an independent predic- tor of optimal immunological recovery after adjustment for baseline CD4 (absolute and percent- age count) and CD4/CD8 ratio. The only independent predictor of first-line ART discontinuation was an initial ART regimen including &gt; 3 drugs. Conclusions: In a large cohort of well-characterized patients with AEHI, we confirmed the ben- eficial role of early ART on CD4+ T-cell recovery and on rates of CD4/CD8 ratio normalization. Moreover, we recognized baseline CD4/CD8 ratio as an independent factor influencing time to virological response in the setting of AEHI, thus giving new insights into research of immunolog- ical markers associated with virological control

Growing old with antiretroviral therapy or elderly people in antiretroviral therapy: two different profiles of comorbidity?

Background In persons living with HIV (PLWH), the burden of non-communicable chronic diseases increased over time, because of aging associated with chronic inflammation, systemic immune activation, and long-term exposure to the combination antiretroviral therapy (ART). Methods To explore the association of chronological age, age at first ART, and exposure to ART with non-communicable chronic diseases, we performed a cross-sectional analysis to evaluate the prevalence of comorbidities in patients enrolled in the SCOLTA Project, stratified by groups of chronological age (50-59 and 60-69 years) and by years of antiretroviral treatment (ART, &lt;= 3 or &gt; 3 years). Results In 1394 subjects (23.8% women), mean age at enrollment was 57.4 (SD 6.5) years, and at first ART 45.3 (SD 10.7). Men were older than women both at enrollment (57.6 vs 56.8, p = 0.06) and at first ART (45.8 vs 43.6, p = 0.0009). ART duration was longer in women (13.1 vs 11.7 years, p = 0.01). The age- and sex-adjusted rate ratios (aRRs, and 95% confidence interval, CI) showed that longer ART exposure was associated with dyslipidemia (aRR 1.35, 95% CI 1.20-1.52), hypertension (aRR 1.52, 95% CI 1.22-1.89), liver disease (aRR 1.78, 95% CI 1.32-2.41), osteopenia/osteoporosis (aRR 2.88, 95% CI 1.65-5.03) and multimorbidity (aRR 1.36, 95% CI 1.21-1.54). These findings were confirmed in strata of age, adjusting for sex. Conclusions Our data suggest that longer ART exposure was associated with increased risk of dyslipidemia, hypertension, and osteopenia/osteoporosis, hence the presence of multimorbidity, possibly due to the exposition to more toxic antiretrovirals. We observed different comorbidities, according to ART exposure and age

Impatto Economico Dei Regimi Semplificati a Base di Raltegravir Nel Trattamento di Mantenimento Dei Pazienti HIV-1 Infetti in Soppressione Virologica:

Budget impact analysis in the maintenance raltegravir-containing regimen in virologically suppressed HIV infected patientsBackgroundA one-year cost analysis was conducted to estimate the impact from the perspective of the Italian National Health Service (NHS) of nevirapine or etravirine or rilpivirine plus raltegravir administration as maintenance antiretroviral therapy in virologically suppressed HIV-1 infected patients.MethodsPatient data were retrieved from the electronic medical record system in use (year 2016) in a reference HIV centre in South Italy. The analysis considered patients with long-term (more than 1 year) virological suppression (HIV-1 RNA <50 copies/mL) on Highly Active Antiretroviral Therapy (HAART) and no prior exposure to integrase inhibitors (INIs). To estimate the total HAART expenditure, we calculated the annual treatment cost for each enrolled patient. Subsequently, to estimate the dual therapy hypothetical expenditure, we assumed to treat the same patients with nevirapine or rilpivirine or etravirine and raltegravir. We took into account only drug costs (ex-factory prices, included all discounts and VAT) from the perspective of the Italian NHS.ResultsIn 2016, the total expenditure for the 116 enrolled HIV-1 infected patients treated with HAART was €869,889. The mean treatment cost per patient was €7,499. If all patients were treated with the dual therapy (nevirapine/raltegravir), the total expenditure would be €641,016 (-26.3%) with a mean treatment cost per patient of €5,526 and a potential total saving of €228,873. On the contrary, the dual regimen based on etravirine or rilpivirine associated with raltegravir would engender respectively a 35.5% and 8.7% expenditure increase.ConclusionsFrom the Italian NHS perspective, nevirapine/raltegravir represent a cost-saving option as maintenance antiretroviral therapy in virologically suppressed HIV-1 infected patients