Nasopharingeal bacterial and fungal colonization in HIV-positive versus HIV-negative adults.

OBJECTIVES: To compare mucosal flora in HIV-positive and HIV-negative subjects, to assess chemosusceptibility patterns of carriage isolates and to evaluate possible predisposing factors within the two groups. METHODS: We analyzed microbes isolated from nasopharyngeal swabs in virologically suppressed and immunologically stable HIV-positive adult outpatients (n=105) at baseline and after 12 months and in an age-matched cohort of HIV-negative outpatients (n=100) at baseline. Bacteria and Candida spp strains were isolated and identified through standard biochemical assays and chemosusceptibility tests were performed. Multi Locus Sequence Typing was also determined to characterize Staphylococcus aureus isolates from HIV-infected persistent carriers. RESULTS: In HIV-positive patients a significantly higher rate of colonization by S. aureus as compared to HIV-negative controls was observed (19% vs 8%, p=0.02), with a relevant percentage of penicillin resistant strains (15% vs 0, p=0.24). Methicillin resistant strains were recovered only from HIV-positive subjects. Overall HIV-positive status was the only predictor of S. aureus colonization (OR 2.77, 95% CI 1.03;7.41, p=0.04). CONCLUSIONS: The nasopharyngeal bacterial flora differs between HIV-positive and HIV-negative subjects and appears relevant for possible development of staphylococcal infections in HIV-positive patients.

Atazanavir/ritonavir with lamivudine as maintenance therapy in virologically suppressed HIV-infected patients: 96 week outcomes of a randomized trial.

Objectives: To investigate the long-term safety and efficacy of a treatment switch to dual ART with atazanavir/ritonavir + lamivudine versus continuing a standard regimen with atazanavir/ritonavir + 2NRTI in virologically suppressed patients. Methods: ATLAS-M is a 96 week open-label, randomized, non-inferiority (margin -12%) trial enrolling HIV-infected adults on atazanavir/ritonavir + 2NRTI, with stable HIV-RNA <50 copies/mL and CD4 counts >200 cells/mm3. At baseline, patients were randomized 1:1 to switch to atazanavir/ritonavir + lamivudine or to continue the previous regimen. Here, we report the 96 week efficacy and safety data. The study was registered with ClinicalTrials.gov, number NCT01599364. Results: Overall, 266 subjects were enrolled (133 in each arm). At 96 weeks, in the ITT population, patients free of treatment failure totalled 103 (77.4%) with atazanavir/ritonavir + lamivudine and 87 (65.4%) with triple therapy (difference +12.0%, 95% CI +1.2/+22.8, P = 0.030), demonstrating the superiority of dual therapy. Two (1.5%) and 9 (6.8%) virological failures occurred in the dual-therapy arm and the triple-therapy arm, respectively, without development of resistance to any study drug. Clinical adverse events occurred at similar rates in both arms. A higher frequency of grade 3-4 hyperbilirubinemia (66.9% versus 50.4%, P = 0.006) and hypertriglyceridaemia (6.8% versus 1.5%, P = 0.031) occurred with dual therapy, although this never led to treatment discontinuation. A significant improvement in renal function and lumbar spine bone mineral density occurred in the dual-therapy arm. The evolution of CD4, HIV-DNA levels and neurocognitive performance was similar in both arms. Conclusions: In this randomized study, a treatment switch to atazanavir/ritonavir + lamivudine was superior over the continuation of atazanavir/ritonavir + 2NRTI in virologically suppressed patients, with a sustained benefit in terms of improved renal function and bone mineral density.

The risk of late or advanced presentation of HIV infected patients is still high, associated factors evolve but impact on overall mortality is vanishing over calendar years: results from the Italian MASTER Cohort.

BACKGROUND: We aimed at evaluating frequency and factors associated with late presentation and advanced HIV disease and excess risk of death due to these conditions from 1985 to 2013 among naïve HIV infected patients enrolled in the Italian MASTER Cohort. METHODS: All antiretroviral naive adults with available CD4+ T cell count after diagnosis of HIV infection were included. Multivariable logistic regression analysis investigated factors associated either with late presentation or advanced HIV disease. Probabilities of survival were estimated both at year-1 and at year-5 according to the Kaplan-Meier method. Flexible parametric models were used to evaluate changes in risk of death overtime according to late presentation and advanced HIV disease. The analyses were stratified for calendar periods. RESULTS: 19,391 patients were included (54 % were late presenters and 37.6 % were advanced presenters). At multivariable analysis, the following factors were positively associated with late presentation: male gender (OR = 1.29), older age (≥55 years vs. <25 years; OR = 7.45), migration (OR = 1.54), and heterosexual risk factor for HIV acquisition (OR = 1.52) or IDU (OR = 1.27) compared to homosexual risk. Survival rates at year-5 increased steadily and reached 92.1 % for late presenters vs. 97.4 % for non-late presenters enrolled in the period 2004-2009. Using flexible parametric models we found a sustained reduction of hazard ratios over time for any cause deaths between late and non-late presenters over time. Similar results were found for advanced HIV disease. CONCLUSION: Screening polices need to be urgently implemented, particularly in most-at-risk categories for late presentation, such as migrants, older patients and those with heterosexual intercourse or IDU as risk factors for HIV acquisition. Although in recent years the impact of late presentation on survival decreased, about 10 % of patients diagnosed in more recent years remains at increased risk of death over a long-term follow-up.

Single tablet regimens are associated with reduced Efavirenz withdrawal in antiretroviral therapy naïve or switching for simplification HIV-infected patients.

BACKGROUND: Efavirenz (EFV) administration is still controversial for its high rates of interruption mainly related to central nervous system side effects (CNS-SE). Aim of the study was to define if single tablet regimen (STR) as compared to bis-in-die (BID) or once-daily (OD) with ≥2 pills-a-day EFV formulations reduced the risk of interruption. METHODS: Patients starting any cART regimen including EFV + 2NRTIs or switching to EFV + 2NRTIs for simplification after virological suppression were retrospectively selected. Incidence, probability and prognostic factors of interruption by different causes were assessed by survival analysis and Cox regression model. RESULTS: Overall, 553 patients starting EFV-containing regimens were included: 38.2% started BID regimen, 44.5% OD regimens ≥2 pills and 17.4% STR. The overall proportion of EFV interruption was 37.4% at 4 years; at the same time point, interruptions for virological failure and toxicity were 8.8% and 16.5% (8% for CNS-SE), respectively. Starting EFV co-formulated in STR was associated with lower proportion of overall interruption at 4 years (17.1% vs. 40.6%, p < 0.01). Only one virological failure was observed with STR up to 4 years (1.1% vs. 10.3% in non-STR, p = 0.051). STR also accounted for lower proportion of interruption by patient decision (1.5% vs. 11.8%, p = 0.01). No differences of interruption by overall toxicity and CNS-SE were observed. In multivariable analysis, STR and male gender were associated with lower risk of EFV interruption, while higher CD4 nadir and IDU with higher risk. CONCLUSIONS: In our experience, starting EFV co-formulated in STR was associated with lower virological failure and higher adherence, despite a similar proportion of CNS toxicity, thus reducing the risk of treatment interruption.

Safety and efficacy of treatment switch to raltegravir plus tenofovir/emtricitabine or abacavir/lamivudine in patients with optimal virological control: 48-week results from a randomized pilot study (Raltegravir Switch for Toxicity or Adverse Events, RASTA Study).

BACKGROUND: The Raltegravir Switch for Toxicity or Adverse Events (RASTA) Study is a 2-arm randomized pilot study exploring the safety and efficacy at 48 weeks of a treatment switch to raltegravir associated with tenofovir/emtricitabine or abacavir/lamivudine in patients with regimens with optimal virological control. METHODS: Patients treated with stable protease inhibitor (PI)-, non-nucleoside reverse transcriptase inhibitor (NNRTI)-, or nucleoside reverse transcriptase inhibitor (NRTI)-based regimens, with HIV-RNA levels < 50 copies/ml for ≥ 3 months and a CD4 cell count > 200 cells/µl were eligible. Enrollment of 40 patients was planned: at baseline patients were randomized 1:1 to switch to raltegravir plus tenofovir/emtricitabine (arm A) or abacavir/lamivudine (arm B). Laboratory parameters, raltegravir plasma levels, self- reported adherence, quality of life parameters, neurocognitive performance, bone composition, and body fat distribution were monitored. Virological failure was defined as HIV-RNA > 50 copies/ml on 2 consecutive determinations. RESULTS: After 48 weeks, 5/40 (12.5%) regimen discontinuations occurred: 2 were for low-level viremia virological failure (both in arm A, at weeks 24 and 48) and 3 were for adverse events (neurological disturbances and skin rash in arm B; proximal tubulopathy in arm A). Overall, a significant CD4 increase was observed at weeks 36 and 48, and a significant decrease in total cholesterol, non-high density lipoprotein cholesterol, and triglycerides was observed at each study visit. Physical health/satisfaction in therapy scores and neuropsychological performance improved. The lumbar column Z-score improved, with no modification in other bone composition and fat distribution parameters. CONCLUSIONS: The investigated switch strategy was associated with rare virological failure. Improvements in lipid levels, quality of life measures, neuropsychological performance, and bone composition suggest good tolerability of raltegravir-based regimens.

Intravenous fosfomycin for treatment of severe infections caused by carbapenem-resistant Acinetobacter baumannii: A multi-centre clinical experience.

BACKGROUND: Severe infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) have been reported increasingly over the past few years. Many in-vivo and in-vitro studies have suggested a possible role of intravenous fosfomycin for the treatment of CRAB infections. METHODS: This multi-centre, retrospective study included patients treated with intravenous fosfomycin for severe infections caused by CRAB admitted consecutively to four hospitals in Italy from December 2017 to December 2022. The primary goal of the study was to evaluate the risk factors associated with 30-day mortality in the study population. A propensity score matched analysis was added to the model. RESULTS: One hundred and two patients with severe infections caused by CRAB treated with an intravenous fosfomycin-containing regimen were enrolled in this study. Ventilator-associated pneumonia (VAP) was diagnosed in 59% of patients, primary bacteraemia in 22% of patients, and central-venous-catheter-related infection in 16% of patients. All patients were treated with a regimen containing intravenous fosfomycin, mainly in combination with cefiderocol (n=54), colistin (n=48) or ampicillin/sulbactam (n=18). Forty-eight (47%) patients died within 30 days. Fifty-eight (57%) patients experienced clinical therapeutic failure. Cox regression analysis showed that diabetes, primary bacteraemia and a colistin-containing regimen were independently associated with 30-day mortality, whereas adequate source control of infection, early 24-h active in-vitro therapy, and a cefiderocol-containing regimen were associated with survival. A colistin-based regimen, A. baumannii colonization and primary bacteraemia were independently associated with clinical failure. Conversely, adequate source control of infection, a cefiderocol-containing regimen, and early 24-h active in-vitro therapy were associated with clinical success. CONCLUSIONS: Different antibiotic regimens containing fosfomycin in combination can be used for treatment of severe infections caused by CRAB.

Safety and feasibility of treatment simplification to atazanavir/ritonavir + lamivudine in HIV-infected patients on stable treatment with two nucleos(t)ide reverse transcriptase inhibitors + atazanavir/ritonavir with virological suppression (Atazanavir and Lamivudine for treatment Simplification, AtLaS pilot study).

OBJECTIVES: To explore 48 week safety and efficacy of treatment simplification to atazanavir/ritonavir + lamivudine in HIV-infected patients with virological suppression on a stable atazanavir/ritonavir-based standard triple regimen. METHODS: This was a single-arm pilot study, enrolling 40 patients on atazanavir/ritonavir + two nucleos(t)ide reverse transcriptase inhibitors (NRTIs), without previous treatment failure, with HIV-RNA <50 copies/mL for >3 months and CD4 >200 cells/mm(3). At baseline, patients were switched to 300/100 mg of atazanavir/ritonavir + 300 mg of lamivudine once daily. Laboratory parameters, atazanavir plasma levels, self-reported adherence, quality of life, neurocognitive performance, bone composition and body fat distribution were monitored. Virological failure was defined as HIV-RNA >50 copies/mL on two consecutive determinations or a single level >1000 copies/mL. RESULTS: After 48 weeks, 4/40 (10%) regimen discontinuations occurred: 1 death (brain haemorrhage), 1 study withdrawal (inadequate atazanavir plasma levels), 1 re-induction with two NRTIs due to pregnancy and 1 virological failure without development of resistance. Seven moderate to severe adverse events were recorded (including four renal colics, possibly treatment-related) in six patients. At week 48, increases in total (mean change +17 mg/dL, P = 0.001), high-density lipoprotein (+6 mg/dL, P < 0.001) and low-density lipoprotein (+8 mg/dL, P = 0.052) cholesterol were observed. The glomerular filtration rate improved (+7 mL/min/1.73 m(2), P < 0.001), as did scores exploring self-reported physical and mental health (+11, P = 0.009 and +13, P < 0.001 on a 0-100 scale), neuropsychological performance (-1 pathological task, P = 0.002) and total bone mineral density (+0.03 g/cm(2), P = 0.026). There were no significant changes in CD4 cell count, bilirubin, atazanavir plasma levels, adherence and body fat distribution over time. CONCLUSIONS: Simplification to atazanavir/ritonavir + lamivudine was apparently safe and associated with rare virological failure, without resistance selection. This strategy deserves further investigation in a randomized trial.

The association of high-sensitivity c-reactive protein and other biomarkers with cardiovascular disease in patients treated for HIV: a nested case-control study.

BACKGROUND: Elevated high-sensitivity C-reactive protein (hsCRP) increases the risk of cardiovascular disease (CVD) in the general population, but its role as a predictive marker in HIV-positive patients remains unclear. Aim of the study was to evaluate whether hsCRP or other biomarkers are independent predictors of CVD risk in HIV-infected patients. METHODS: Retrospective, nested case-control study. HIV-positive men and women (35-69 years of age) receiving combination antiretroviral therapy (cART) were included. Cases (n = 35) had a major CVD event. Controls (n = 74) free from CVD events for at least 5 years from starting ART were matched on diabetes and smoking. HsCRP, D-dimer, P-selectin, interleukin-6 (IL-6), tissue plasminogen activator, plasminogen activator inhibitor-1 levels were measured. RESULTS: High hsCRP was associated with CVD risk, independently of traditional cardiovascular risk factors, HIV replication and the type of ART received at the time of sampling (adjusted odds ratio 8.00 [1.23-51.94] comparing >3.3 mg/L with <0.9 mg/L; P = 0.03). Higher IL-6 and P-selectin levels were also independently associated with increased CVD risk, although the association was weaker than for hsCRP. Higher total cholesterol and lower HDL cholesterol increased CVD risk, independent of hsCRP. CONCLUSION: hsCRP may be a useful additional biomarker to predict CVD risk in HIV-infected patients receiving cART.

Predictors of first-line antiretroviral therapy discontinuation due to drug-related adverse events in HIV-infected patients: a retrospective cohort study.

BACKGROUND: Drug-related toxicity has been one of the main causes of antiretroviral treatment discontinuation. However, its determinants are not fully understood. Aim of this study was to investigate predictors of first-line antiretroviral therapy discontinuation due to adverse events and their evolution in recent years. METHODS: Patients starting first-line antiretroviral therapy were retrospectively selected. Primary end-point was the time to discontinuation of therapy due to adverse events, estimating incidence, fitting Kaplan-Meier and multivariable Cox regression models upon clinical/demographic/chemical baseline patients' markers. RESULTS: 1,096 patients were included: 302 discontinuations for adverse events were observed over 1,861 person years of follow-up between 1988 and 2010, corresponding to an incidence (95% CI) of 0.16 (0.14-0.18). By Kaplan-Meier estimation, the probabilities (95% CI) of being free from an adverse event at 90 days, 180 days, one year, two years, and five years were 0.88 (0.86-0.90), 0.85 (0.83-0.87), 0.79 (0.76-0.81), 0.70 (0.67-0.74), 0.55 (0.50-0.61), respectively. The most represented adverse events were gastrointestinal symptoms (28.5%), hematological (13.2%) or metabolic (lipid and glucose metabolism, lipodystrophy) (11.3%) toxicities and hypersensitivity reactions (9.3%). Factors associated with an increased hazard of adverse events were: older age, CDC stage C, female gender, homo/bisexual risk group (vs. heterosexual), HBsAg-positivity. Among drugs, zidovudine, stavudine, zalcitabine, didanosine, full-dose ritonavir, indinavir but also efavirenz (actually recommended for first-line regimens) were associated to an increased hazard of toxicity. Moreover, patients infected by HIV genotype F1 showed a trend for a higher risk of adverse events. CONCLUSIONS: After starting antiretroviral therapy, the probability of remaining free from adverse events seems to decrease over time. Among drugs associated with increased toxicity, only one is currently recommended for first-line regimens but with improved drug formulation. Older age, CDC stage, MSM risk factor and gender are also associated with an increased hazard of toxicity and should be considered when designing a first-line regimen.

Performance of a multicompounds nutraceutical formulation in patients with symptomatic uncomplicated diverticular disease.

BACKGROUND: Symptomatic uncomplicated diverticular disease (SUDD) is a recognized clinical condition characterized by abdominal pain and changes in bowel habits, attributed to diverticula but without macroscopic signs of diverticulitis. There is no consensus about the management of these patients. Enteroflegin®, an association of natural active ingredients, could be effective in the treatment of those patients. METHODS: We conducted a retrospective observational study to evaluate the performances of Enteroflegin® in patients with SUDD. Patients were treated with Enteroflegin® 2 cp/day for 10 days per month for 6 months. Primary endpoint was the clinical remission rate, defined as the absence of any symptoms; secondary endpoints were the impact of the treatment on reduction of symptoms, on fecal calprotectin (FC) expression, and the prevention of acute diverticulitis. RESULTS: Three hundred and fifty patients were retrospectively enrolled (183 males, median age 64 years, IQR 54-70). Enteroflegin® was effective in inducing remission in 9.34% and 17.64% of patients at 3 and 6 months respectively (P<0.001). Reduction of symptoms occurred in 92.3% and in 85.3% of patients at 3 and 6 months respectively (P<0.001), and symptoms' recurrence or worsening was recorded in only 1.71% of patients during the follow-up. FC expression dropped from 181.3 µg/g at baseline to 100.2 µg/g (P<0.001) and to 67.9 µg/g (P<0.001) at 3 and 6 months of follow-up respectively. No adverse event was recorded during the follow-up. Finally, acute diverticulitis occurred in just 2% of patients during the follow-up. CONCLUSIONS: Enteroflegin® seems to be an effective nutraceutical compound in obtaining remission and symptom relief in SUDD patients. Further randomized, placebo-controlled clinical trials are needed to confirm these preliminary data.

Prospective evaluation of epidemiological, clinical, and microbiological features of pandemic influenza A (H1N1) virus infection in Italy.

Since several characteristics of pandemic influenza A (H1N1) virus infection remain to be determined, this study aimed to describe clinical features and complications of patients infected with H1N1. Subjects affected by influenza-like illnesses and a control group of asymptomatic patients were enrolled prospectively at an Emergency Department from October 2009 to April 2010. At enrollment, clinical data and nasopharyngeal swabs for virological analyses were obtained. Ill subjects were followed until recovery and swabs were collected weekly in patients infected with H1N1. Of 318 patients enrolled, 92 (28.9%) were positive to H1N1. Patients infected with H1N1 were mainly young adults and complained classic influenza-like symptoms. Fever was observed for a median time of 5 (IQR 3-7) days. Hospitalization occurred in 27.7% with 2% requiring intensive care unit admission: median length of hospitalization was 6 days (IQR 5-9). Pneumonia was diagnosed in 19.6% of patients. A similar proportion of lower airways involvement and of clinical complications was observed in subjects testing positive or negative for H1N1. However, patients infected with H1N1 were younger and hospitalized for a shorter period as compared to the control group (P = 0.002 and P = 0.045, respectively). Older age, asthma/chronic obstructive pulmonary disease and hypertension were associated with an increased risk of pneumonia. Viral shedding was observed for at least 1 week in 21.3% of patients. Asymptomatic infection was uncommon (1.1%). Respiratory syndromes caused by H1N1 and factors associated with disease severity were investigated and compared to influenza-like illnesses of other origin. Such findings might contribute to improve clinical and epidemiological management of the disease.

Efficacy of a Fosfomycin-Containing Regimen for Treatment of Severe Pneumonia Caused by Multidrug-Resistant Acinetobacter baumannii: A Prospective, Observational Study.

INTRODUCTION: Severe pneumonia caused by multidrug-resistant Acinetobacter baumannii (MDR-AB) remains a difficult-to-treat infection. Considering the poor lung penetration of most antibiotics, the choice of the better antibiotic regimen is debated. METHODS: We performed a prospective, observational, multicenter study conducted from January 2017 to June 2020. All consecutive hospitalized patients with severe pneumonia due to MDR-AB were included in the study. The primary endpoint of the study was to evaluate risk factors associated with survival or death at 30 days from pneumonia onset. A propensity score for receiving therapy with fosfomycin was added to the model. RESULTS: During the study period, 180 cases of hospital-acquired pneumonia, including ventilator-associated pneumonia, caused by MDR-AB strains were observed. Cox regression analysis of factors associated with 30-day mortality, after propensity score, showed that septic shock, and secondary bacteremia were associated with death, while a fosfomycin-containing regimen was associated with 30-day survival. Antibiotic combinations with fosfomycin in definitive therapy for 44 patients were: fosfomycin + colistin in 11 (25%) patients followed by fosfomycin + carbapenem + tigecycline in 8 (18.2%), fosfomycin + colistin + tigecycline in 7 (15.9%), fosfomycin + rifampin in 7 (15.9%), fosfomycin + tigecycline in 6 (13.6%), fosfomycin + carbapenem in 3 (6.8%), and fosfomycin + aminoglycoside in 2 (4.5%). CONCLUSIONS: This real-life clinical experience concerning the therapeutic approach to severe pneumonia caused by MDR-AB provides useful suggestions to clinicians, showing the use of different antibiotic regimens with a predominant role for fosfomycin. Further randomized clinical trials are necessary to confirm or exclude these observations.

Hot Topics in Medical Treatment of Diverticular Disease: Evidence Pro and Cons.

Symptomatic Uncomplicated Diverticular Disease (SUDD) is the most common clinical form of Diverticular Disease (DD). The therapy should be aimed at reducing both the intensity and frequency of symptoms as well as preventing complications. The pharmacological treatments include fibers, not absorbable antibiotics (for example rifaximin), anti-inflammatory drugs (for example 5-amino-salycilic acid) and probiotics, alone or in combination with other drugs. Although some of these treatments seem to be effective in treating SUDD, but their efficacy in preventing complications of the disease is still uncertain. It has been hypothesized that microbial imbalance associated with bacterial overgrowth of the colon, may be the key to the development of diverticular disease (DD). Therefore, drugs that can manipulate gut microbiota such as probiotics or rifaximine are considered as a potential key therapy. Rifaximine is able to modulate the intestinal ecosystem, restoring eubiosis. Traditionally, DD of the colon is thought to be related to low grade of inflammation. By analogy with other inflammatory bowel diseases mesalazine has been studied also in DD. There are several evidences that may support the use of mesalazine in the SUDD. Unfortunately, mesalazine cannot be used to prevent diverticulitis because of the paucity of high-quality studies. Currently, mesalazine has a limited place for the management of SUDD. In SUDD probiotics have been proven as an effective therapy in reducing abdominal symptoms, but unfortunately there has been limited number of relevant studies regarding efficacy of this therapy.

3-Year efficacy and durability of simplification to single tablet regimens: a comparison between co-formulated efavirenz/emtricitabine/tenofovir and rilpivirine/emtricitabine/tenofovir.

BACKGROUND: Few data are available about efficacy and durability of simplification from multi-tablet antiretroviral regimens to co-formulated efavirenz (EFV)/emtricitabine (FTC)/tenofovir (TDF) versus rilpivirine (RPV)/FTC/TDF in virologically suppressed HIV-1-infected patients. METHODS: We retrospectively analysed HIV-infected patients with HIV RNA <50 copies/ml switching to co-formulated EFV/FTC/TDF or RPV/FTC/TDF at five Italian centres. Patients were followed from time of switch until regimen discontinuation or a maximum of 3-years follow-up. Time to treatment discontinuation (TD) and virological failure (VF; defined as two consecutive HIV RNA >50 copies/ml or a single determination >1,000 copies/ml) and their predictors were investigated. RESULTS: 1,560 patients were reviewed of which 1,097 (70%) switched to EFV/FTC/TDF and 463 (30%) to RPV/FTC/TDF. During follow-up, VF and TD occurred in 44 (4%) and 242 (22%) patients in EFV/FTC/TDF and in 29 (6%) and 50 (11%) patients in RPV/FTC/TDF, respectively. The 3-year estimated probability of remaining free from VF was 96.2% with EFV/FTC/TDF versus 92.7% with RPV/FTC/TDF (P=0.003). At multivariate analysis, regimen type (EFV/FTC/TDF versus RPV/FTC/TDF aHR 0.24; P=0.004) and time of virological suppression (aHR 0.85; P=0.048) were the only independent predictors of VF. The estimated 3-year probability of remaining free from TD was 77.4% with EFV/FTC/TDF versus 88.4% with RPV/FTC/TDF (P=0.001). Predictors of TD were female sex, switching from PI-based regimens, older age, shorter time of virological suppression and regimen type (EFV/FTC/TDF versus RPV/FTC/TDF aHR 2.48; P<0.001). RPV/FTC/TDF showed a safer lipid profile and a greater increase in creatinine. CONCLUSIONS: Both regimens showed good safety and efficacy in this real-life setting, although switch to RPV/FTC/TDF seemed better tolerated while EFV/FTC/TDF was associated with a lower probability of VF.

Changes in bone mineral density in HIV-positive, virologically suppressed patients switching to lamivudine/dolutegravir dual therapy: preliminary results from clinical practice.

Bone toxicity is a well-known side effect of several antiviral agents. In a cohort of virologically suppressed HIV-infected patients, we investigated the effects of a lamivudine/dolutegravir dual therapy on bone mineral density (BMD). We observed a significant improvement in lumbar spine BMD as well as T-score after 12 months of observation with concomitant bisphosphonate therapy independently predicting a greater improvement. These preliminary data show a favorable effect of this 2-drug regimen on bone health.

Lipid-lowering effect and changes in estimated cardiovascular risk after switching to a tenofovir-containing regimen for the treatment of HIV-infected patients.

Tenofovir could have a direct lipid-lowering effect. The aim of our retrospective study was to investigate changes in cardiovascular risk after switching from a tenofovir-sparing to a tenofovir-containing backbone. Lipid parameters and cardiovascular risk [calculated using 10-years Framingham Risk Score (FRS) and 5-years DAD Risk Score (DRS)] were analysed at baseline and after three months. 273 patients were enrolled. After switching, significant decreases in total cholesterol (TC) (-8.2mg/dl, p < 0.001), LDL (-8.7mg/dl, p < 0.001) and DRS (mean -0.26%, p < 0.001) were observed, while a reduction in FRS was only observed in patients with pre-switch high TC or medium-high (>10%) FRS. Pre-switch factors associated with DRS reduction were higher TC, abacavir, new generation protease inhibitors, while zidovudine predicted an increase of DRS. Our results suggest that the improvement of lipid parameters observed after switching to a tenofovir-containing backbone could lead to a significant reduction in predicted cardiovascular risk, which became more evident in subjects with higher cardiovascular risk.

Switch to maraviroc with darunavir/r, both QD, in patients with suppressed HIV-1 was well tolerated but virologically inferior to standard antiretroviral therapy: 48-week results of a randomized trial.

OBJECTIVES: Primary study outcome was absence of treatment failure (virological failure, VF, or treatment interruption) per protocol at week 48. METHODS: Patients on 3-drug ART with stable HIV-1 RNA <50 copies/mL and CCR5-tropic virus were randomized 1:1 to maraviroc with darunavir/ritonavir qd (study arm) or continue current ART (continuation arm). RESULTS: In June 2015, 115 patients were evaluable for the primary outcome (56 study, 59 continuation arm). The study was discontinued due to excess of VF in the study arm (7 cases, 12.5%, vs 0 in the continuation arm, p = 0.005). The proportion free of treatment failure was 73.2% in the study and 59.3% in the continuation arm. Two participants in the study and 10 in the continuation arm discontinued therapy due to adverse events (p = 0.030). At VF, no emergent drug resistance was detected. Co-receptor tropism switched to non-R5 in one patient. Patients with VF reported lower adherence and had lower plasma drug levels. Femoral bone mineral density was significantly improved in the study arm. CONCLUSION: Switching to maraviroc with darunavir/ritonavir qd in virologically suppressed patients was associated with improved tolerability but was virologically inferior to 3-drug therapy.

Neuropsychological screening tools in Italian HIV+ patients: a comparison of Montreal Cognitive Assessment (MoCA) and Mini Mental State Examination (MMSE).

OBJECTIVE: Despite the progress in HIV treatments, mild forms of cognitive impairment still persist. Brief and sensitive screening tools are needed. We evaluated the accuracy of the Montreal Cognitive Assessment (MoCA) compared to the Mini Mental State Examination (MMSE) to detect cognitive impairment in HIV-infected participants. METHOD: HIV-infected patients were consecutively enrolled during routine outpatient visits at a single institution. The MoCA, the MMSE, and a comprehensive neuropsychological battery were administered. Patients were considered as affected by cognitive impairment if they showed decreased cognitive function in at least two ability domains based on age and education adjusted Italian normative cut-offs. RESULTS: Ninety-three HIV-infected participants (75% males, median age 47, all on antiretroviral therapy; 90% HIV-RNA <50copies/mL, median CD4 644 cells/µL) were enrolled. Thirteen participants (14%) were diagnosed as cognitively compromised via a comprehensive neuropsychological examination. The area under the curve of the adjusted MMSE and MoCA scores to detect cognitive impairment were .51 (95% CI = .31-.72, p = .877) and .70 (95% CI = .53-.86, p = .025), respectively. A MoCA score <22 was able to predict the cognitive impairment with 62% of sensitivity and 76% of specificity. CONCLUSIONS: Our findings suggested that the prognostic performance of the MoCA to detect cognitive impairment among mildly impaired HIV-infected participants was only moderate. Further investigations are needed to identify optimal cognitive tests to screen HIV-infected individuals or to explore whether a combination of cognitive tests might represent a viable alternative to a single screening tool.

Liver fibrosis is associated with cognitive impairment in HIV-positive patients.

INTRODUCTION: The aim of our study was to investigate the potential relationship between liver fibrosis (LF) and cognitive performance in HIV+ patients. MATERIALS AND METHODS: We performed a cross-sectional cohort study by consecutively enrolling HIV+ patients during routine outpatient visits at two clinical centres in Italy. Subjects with decompensated liver disease were excluded. All subjects underwent a comprehensive neuropsychological battery exploring memory, attention, psychomotor speed and language; cognitive impairment was defined as at least two abnormal [1.5 SD below the mean for appropriate norms] cognitive domains. LF was explored by calculating FIB4 index; in a subgroup of patients, LF was also assessed by transient elastography. Factors associated with cognitive impairment were investigated by logistic regression models. RESULTS: A total of 413 patients [77% males, median age 46 (IQR 39-52), 17% with past AIDS-defining events, 19% past IDU, 3% with diabetes, 94% on cART, 90% with HIV RNA <50 copies/mL, 18% co-infected with HCV] were enrolled. Seventeen patients (4%) had FIB4 >3.25 and 14/129 (3%) had liver stiffness >14KPa. Forty-seven patients (11%) were diagnosed with cognitive impairment. At multivariate analyses patients with FIB4 >1.45 showed a higher risk of cognitive impairment in comparison with those with lower values (OR 2.19, 95% CI 1.02-4.72; p=0.044) after adjusting for education (OR 0.79, 95% CI 0.71-0.88; p<0.001), past IDU (OR 1.69, 95% CI 0.67-4.23; p=0.264), diabetes (OR 2.35, 95% CI 0.62-8.86; p=0.207), HIV RNA <50 copies/mL (OR 0.47, 95% CI 0.19-1.14; p=0.095) and HCV co-infection (OR 0.88, 95% CI 0.33-2.39; p=0.807). Analyzing any single cognitive domain, a higher risk of abnormal psychomotor speed was associated with fibroscan score >14KPa in comparison with fibroscan score <7KPa (OR 285.07; 95% CI 2.42-33574.06; p=0.020) after adjusting for education (OR 0.54, 95% CI 0.31-0.92; p=0.024), age (for 10 years increase) (OR 2.03, 95% CI 0.55-7.53; p=0.288), past IDU (OR 4.43, 95% CI 0.35-7.57; p=0.526), HIV RNA <50 copies/mL (OR 0.01, 95% CI 0.00-0.18; p=0.003), HIV history (for 1 year increase) (OR 0.96, 95% CI 0.83-1.12; p=0.641), CD4 cells count at nadir (OR 1.10, 95% CI 0.56-2.16; p=0.779), and HCV co-infection (OR 0.06; 95% CI 0.00-1.93; p=0.113). CONCLUSIONS: In HIV-infected patients higher LF, estimated through non-invasive methods, is associated to a higher risk of cognitive impairment.