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The care engagement of people living with HIV (PLWH) measured with the patient health engagement (PHE) model and its association with HIV-related internalized stigma are not well established. Indeed, currently there are no data yet about the engagement of PLWH measured with the PHE model. This study aimed to evaluate the effects of HIV-related internalized stigma on care engagement and mental health and to fill the lack of data on PHE model applied to PLWH. We found that the internalized stigma score was significantly higher for PLWH ( n =82) in worse care engagement phase and both higher internalized stigma scores and worse engagement were associated to major depression symptoms.In conclusion, our findings describe for the first time the engagement in care of PLWH measured with PHE and highlight the importance of PLWH support to find strategies to cope stigma-related stress and optimize their care engagement.

Based on the available literature, women living with HIV (WLWH) seem to show greater cognitive and emotional disadvantages than men living with HIV (MLWH). Our aim was to compare the cognitive performance of MLWH and WLWH in an Italian cohort of People Living With HIV (PLWH) and to analyse factors potentially contributing to sex differences in cognitive function. We ran a retrospective, cross-sectional analysis of a monocentric dataset of PLWH who were administered a standardized neuropsychological test battery (SNB) during routine clinical care. We enrolled 161 Italian PLWH who are on combined antiretroviral therapy (cART): 114 (70.8%) MLWH and 47 (29.2%) WLWH.Global cognitive performance (composite z score) (GCP) was significantly higher in MLWH than WLWH [mean 0.19 (SD 0.85) vs - 0.13 (SD 0.96); p = 0.039]. Moreover, WLWH obtained significantly higher scores on the Zung Depression Scale than MLWH [mean 41.8 (SD 10.9) vs 36.7 (SD 9.2); p = 0.003]. However, there was no statistically significant direct effect between male sex and better GCP (p = 0.692) in the context of a mediation model. On the contrary, the associations between male sex and better GCP were mediated by higher level of education (a*b =  + 0.15, Bootstrap CI95 = 0.05 and 0.27) and a lower Zung depression score (a*b =  + 0.10, Bootstrap CI95 = 0.02 and 0.21).In conclusion, the global cognitive performance of WLWH is lower than that of MLWH. However, other demographic and clinical factors besides sex might help explain differences in their neurocognitive functions and make it possible for us to monitor them and identify those patients most in need., (© 2022. The Author(s).)

Background: The COVID-19 pandemic has changed outpatient clinical practice, which has led to the need defining digital healthcare modalities to provide telehealth services. The aim of our study was to explore opinions about HIV management via telehealth in a representative, southern central Italian cohort of individuals with HIV (PLWH) and doctors involved in the treatment process., Methods: We enrolled 80 PLWH who have never used telehealth tools and 60 doctors, who administered an anonymous self-report questionnaire to investigate their opinions about telehealth service use., Results: Most of the doctors and patients indicated that they would use telehealth services; however, 88.3% of the doctors and 40% of the PLWH did not want to substitute personal visits with telehealth services. Unlike PLWH, physicians seemed to agree with most of the possible risks of telehealth, such as patients' isolation from the hospital system (71.7%), interaction difficulty (46.7%) and lower quality of patient assessment (63.3%). The doctors focused on the qualitative aspects of telehealth services reducing patients' exposure to stigma (61.7%), improving quality of patient care (41.7%), and improving privacy (58.3%). By contrast, patients focused on the quantitative aspects of telehealth services improving timely access to care (44%), time saving (63%) and improving interaction with doctor (43%)., Conclusions: Both PLWH (especially older patients and those with longer experience of disease management) and doctors welcome the use of telehealth services but disagree using it to substitute medical consultation in person focusing on different possible benefits and risks of telehealth depending on the needs expressed. Thus, our results suggest the need to initiate and expand communication about telehealth between doctors and patients., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The aim of this study was to explore the psychological impact of the initial stage of the 2019 coronavirus (COVID-19) pandemic on people living with HIV (PLWH), a population at increased risk of psychological distress. PLWH participated in an online survey exploring demographic and clinical data, physical symptoms, contact history, knowledge and concerns, precautionary measures and additional information about COVID-19 during the first phase of the pandemic in Italy. The Impact of Event Scale-Revised (IES-R) (identifying the COVID-19 pandemic as a specific traumatic life event) and the Depression, Anxiety and Stress Scale (DASS-21) also formed part of the survey. Out of 98 participants, 45% revealed from mild to severe psychological impact from COVID-19 according to IES-R. A lower percentage, instead, complained of significant levels of depression (14%), anxiety (11%) or stress (6%) according to DASS-21. Higher education, being unemployed, number of perceived COVID-19 physical symptoms, concerns about risk of contracting COVID-19 and the pandemic situation in Italy, and needing additional information to prevent COVID-19 infection were positively associated to a higher risk of negative psychological impact. Moreover, among the participants, female gender, age, fewer years from HIV diagnosis and not being aware of their own viremia were associated to a higher risk of negative psychological outcomes. Almost half of our PLWH sample experienced significant levels of distress related to the COVID-19 pandemic. Women, elderly patients and those with recent HIV diagnosis appear to be the more psychologically fragile subgroups. Our findings could help identify patients most in need of psychological interventions to improve the wellbeing of PLWH.

Everyday functioning (EF) impairment is frequent in people living with HIV (PLWH). Our aim was to better explore EF and its association with PLWH cognition, by administering both the IADL scale, the most common functional scale, and a new and ecologic multi-domain (communication and financial skills) tool to measure EF as the University of California San Diego (UCSD) Performance-Based Skills Assessment-Brief Version (UPSA-B). Eighty-five PLWH on cART with very good immunological condition and 23 age- and education-matched healthy controls (HC) were enrolled. PLWH underwent a standardized neuropsychological battery plus IADL, and cognitive impairment was defined according to Frascati criteria. Both groups underwent the UPSA-B. Only 6 subjects (7%) were affected by cognitive impairment (asymptomatic profile). While IADL score was at ceiling for all patients, the UPSA-B total score was significantly worse in PLWH when compared with HC [mean 82.1 (SD 9.3) vs 89.2 (SD 6.2); p < 0.001]. At communication subtest, PLWH group and HC were significantly different (p = 0.002), while no difference emerged at financial skills (p = 0.096). Higher score at UPSA-B was independently associated with better global cognitive performance (composite Z-score) (β 7.79; p < 0.001). Also considering each single cognitive domain, UPSA-B performance (both total and at subtests) confirmed the association with neurocognitive performance. In conclusion, UPSA-B seems to better discriminate EF impairment than IADL in PLWH, and it was associated with cognitive functions, also in the absence of symptomatic cognitive impairment. Thus, it appears a promising tool in the context of HIV infection to avoid misdiagnosis and to better detect also mild EF.

Aims: The prognosis and the clinical manifestations of HIV infection have changed with the introduction of the potent combination antiretroviral therapy (cART); however, up to 50% of patients meet research criteria for "HIV-associated neurocognitive disorders" (HAND) according with current nosology. The majority of patients affected by HAND, especially in cohorts with suppressed plasma viremia, showed an Asymptomatic Neurocognitive Impairment (ANI), without any functional impairment. After more than 10 years from the introduction of the current so-called "Frascati criteria", this mini-review aimed to address the emerging limitations in current diagnosis procedures., Methods: We discussed the most relevant literature on HAND prevalence, etiology, and diagnosis., Results: We addressed three main emerging issues: (1) the unclear clinical relevance of ANI entity; (2) the evidences that Frascati criteria could produce a significant overestimation of HAND; (3) the need to better identify patients with a higher risk to develop HAND requiring routine neuropsychological examinations., Conclusions: Frascati criteria should be updated to better respond to the present characteristics of HIV + cohorts and to help clinicians in their cognitive and global management.

The contribution of HCV-related variables to cognitive impairment in HIV-HCV-coinfected patients has been poorly investigated. We selected HIV-HCV-coinfected patients undergoing cognitive examination (exploring memory, language, speed of mental processing and fine motor function) at three clinical centres. Cognitive performance was evaluated using Z-transformed scores. Logistic regression analysis was used to investigate variables associated to cognitive impairment (defined as a composite Z-score ≤ - 1). Overall, 146 HIV-HCV-coinfected patients were enrolled. Median HCV-RNA was 6.2logU/mL. HCV genotype 1a/b was the most represented (53.4%). Liver fibrosis was mild (Fib4 ≤ 1.45) in the majority of patients (44.5%). Global cognitive impairment was diagnosed in 35 (24%) subjects. Exploring each domain, a higher proportion of impairment was observed for memory (37%) followed by speed of mental processing (32.2%), fine motor functioning (24%) and language (18.5%). Among HCV-related variables, the duration of HCV infection was independently associated with global cognitive impairment (aOR 1.13 per +1 year, p = 0.016) and abnormal speed of mental processing (aOR 1.16 per +1 year, p = 0.001), while higher HCV-RNA was independently associated to fine motor functioning impairment (aOR 1.98 per +1log, p = 0.037). HCV genotype, fibrosis stage, transaminases or bilirubin levels were not related to cognitive performance. Of note, integrase inhibitor (InSTI) use was independently associated to a pathological performance in fine motor functioning (aOR 3.34, p = 0.035) and memory (aOR 3.70, p = 0.014). In conclusion, the duration of HCV infection and HCV-RNA load showed an association with cognitive impairment, suggesting a role of hepatitis-related factors in the development of cognitive disorders in HIV-HCV-coinfected patients. The association between InSTI use and altered cognitive performance should prompt investigations about potential neurotoxicity of these drugs.

Both cognitive diseases and alexithymia may be associated with HIV. Moreover, alexithymia has been linked to cardiovascular (CV) diseases. Our aim was to explore the prevalence of alexithymia and its associations with neurocognitive disorders (HAND) and CV risk factors in a well-controlled HIV-positive population. We consecutively enrolled 140 HIV-positive individuals on antiretroviral therapy and 35 healthy subjects matched for age, education and gender. In all participants alexithymia was explored by the 20-item Toronto Alexithymia Scale. For HIV-positive subjects also data about CV risk factors were collected, and a comprehensive neuropsychological examination was administered; HAND was defined according to Frascati criteria. Patients and controls did not differ in the proportion of alexithymic status (10% vs. 11%; p=0.761). Among HIV-positive patients, alexithymic participants presented a higher prevalence of diabetes (21% vs. 3%, p=0.035) and hypertension (36% vs. 13%, p= 0.037) compared to non-alexithymic. About 30% (n=41) of HIV-positive patients met criteria for asymptomatic HAND. Alexithymia was not independently associated with a higher risk of HAND (p=0.189). Analyzing each cognitive domain, alexithymia showed an independent association with an abnormal performance (OR 1.08; p=0.037) only in psychomotor speed. In conclusion, in the context of a well-controlled HIV infection, we found a low prevalence of alexithymia comparable to healthy controls. Alexithymia was linked to higher risk of CV disease in the HIV-positive population, but with a rate similar to that previously estimated in the HIV-negative alexithymic. Finally, alexithymia was clearly associated to cognitive impairment only in the psychomotor speed domain, suggesting a common fronto-striatal system dysregulation.

Purpose: Our aim was to better explore the association between liver fibrosis (LF) and neurocognitive impairment (NCI) in people living with HIV (PLWH)., Methods: We performed a cross-sectional cohort study by consecutively enrolling PLWH at two clinical centers. All subjects underwent a comprehensive neuropsychological battery; NCI was defined as having a pathological performance (1.5 SD below the normative mean) on at least two cognitive domains. LF was explored using FIB4 index; in a subgroup of PLWH, LF was also assessed by transient elastography., Results: A total of 386 subjects were enrolled, of whom 17 (4.4%) had FIB4 > 3.25. In the subgroup of PLWH (N = 127) performing also liver transient elastography, 14 (11%) had liver stiffness > 14 kPa. Overall, 47 subjects (12%) were diagnosed with NCI. At multivariate regression analyses, participants with FIB4 > 1.45 showed a higher risk of NCI in comparison with those with lower values (aOR 3.04, p = 0.044), after adjusting for education (aOR 0.71, p < 0.001), past AIDS-defining events (aOR 2.91, p = 0.014), CD4 cell count, past injecting drug use (IDU), HIV-RNA < 50 copies/mL, and HCV co-infection. Also a liver stiffness > 14 kPa showed an independent association with a higher risk of NCI (aOR 10.13, p = 0.041). Analyzing any single cognitive domain, a higher risk of abnormal psychomotor speed was associated with a liver stiffness > 14 kPa (aOR 223.17, p = 0.019) after adjusting for education (aOR 0.57, p = 0.018), HIV-RNA < 50 copies/mL (aOR 0.01, p = 0.007), age, past IDU, and HCV co-infection., Conclusions: In PLWH, increased LF, estimated through non-invasive methods, was associated to a higher risk of NCI independently from HCV status.

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.

HIV+ population is getting older because of progress in treatments. Yet, there are concerns that Older HIV+ individuals (OHIV+) may be more vulnerable for developing a "cortical" dementia such as Alzheimer Disease (AD). Our aim was to explore the hypothesis that the cognitive deficit extends to ''cortical'' functions in OHIV+ by comparing serial position effects (SPE) in different groups of participants affected by "cortical" or "subcortical" damage. We enrolled a total of 122 subjects: 22 OHIV+ (≥60 years of age), 31 Younger HIV+ (YHIV+) (<60 years of age), 18 participants with AD, 23 subjects with Parkinson Disease (PD), and 28 healthy subjects. All subjects performed verbal learning tasks (VLT) to explore SPE. Factorial analysis of covariance showed a significant effect of "group" (p < 0.001) and "task" (Primacy vs Recency) (p < 0.001), but no significant group*task (p = 0.257) interaction. Compared with healthy subjects (p = 0.003), AD had the most severe reduction of Primacy, confirming a primary "encoding deficit," while PD confirmed a "frontal pattern." OHIV+ showed a memory profile similar to that of PD with a worsening of the cognitive performance in comparison with YHIV+. In conclusion, we did not confirm the "cortical" hypothesis in OHIV+, at least in terms of learning and memory functions.

Background: Combination ART (cART)-related toxicities and costs have prompted the need for treatment simplification. The ATLAS-M trial explored 48 week non-inferior efficacy of simplification to atazanavir/ritonavir  +  lamivudine versus maintaining three-drug atazanavir/ritonavir-based cART in virologically suppressed patients., Methods: We performed an open-label, multicentre, randomized, non-inferiority study, enrolling HIV-infected adults on atazanavir/ritonavir + two NRTIs, with stable HIV-RNA <50 copies/mL and CD4 + >200 cells/mm 3 . Main exclusion criteria were hepatitis B virus coinfection, past virological failure on or resistance to study drugs, recent AIDS and pregnancy. Patients were randomly assigned 1:1 to either switch to 300 mg of atazanavir/100 mg of ritonavir once daily and 300 mg of lamivudine once daily (atazanavir/ritonavir + lamivudine arm) or to continue the previous regimen (atazanavir/ritonavir + two NRTIs arm). The primary study outcome was the maintenance of HIV-RNA <50 copies/mL at week 48 of the ITT-exposed (ITT-e) analysis with switch = failure. The non-inferiority margin was 12%. This study is registered at ClinicalTrials.gov, number NCT01599364., Results: Between July 2011 and June 2014, 266 patients were randomized (133 to each arm). After 48 weeks, the primary study outcome was met by 119 of 133 patients (89.5%) in the atazanavir/ritonavir + lamivudine arm and 106 of 133 patients (79.7%) in the atazanavir/ritonavir + two NRTIs arm [difference atazanavir/ritonavir + lamivudine versus atazanavir/ritonavir + two NRTIs arm: +9.8% (95% CI + 1.2 to + 18.4)], demonstrating non-inferiority and superior efficacy of the atazanavir/ritonavir + lamivudine arm. Virological failure occurred in two (1.5%) patients in the atazanavir/ritonavir + lamivudine arm and six (4.5%) patients in the atazanavir/ritonavir + two NRTIs arm, without resistance selection. A similar proportion of adverse events occurred in both arms., Conclusions: Treatment simplification to atazanavir/ritonavir + lamivudine showed non-inferior efficacy (superiority on post-hoc analysis) and a comparable safety profile over continuing atazanavir/ritonavir + two NRTIs in virologically suppressed patients., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Progress in treatments has led to HIV+ patients getting older. Age and HIV are risk factors for neurocognitive impairment (NCI). We explored the role of cognitive reserve (CR) on cognition in a group of virologically suppressed older HIV+ people. We performed a multicenter study, consecutively enrolling asymptomatic HIV+ subjects ≥60 years old during routine outpatient visits. A comprehensive neuropsychological battery was administered. Raw test scores were adjusted based on Italian normative data and transformed into z-scores; NCI was defined according to Frascati criteria. All participants underwent the Brief Intelligence Test (TIB) and the Cognitive Reserve Index (CRI) questionnaire as proxies for CR. Relationships between TIB, CRI, and NCI were investigated by logistic or linear regression analyses. Sixty patients (85 % males, median age 66, median education 12, 10 % HCV co-infected, 25 % with past acquired immunodeficiency syndrome (AIDS)-defining events, median CD4 cells count 581 cells/μL, median nadir CD4 cells count 109 cells/μL) were enrolled. Twenty-four patients (40 %) showed Asymptomatic Neurocognitive Impairment. At logistic regression analysis, only CRI (OR 0.94; 95 % CI 0.91-0.97; P = 0.001) and TIB (OR 0.80; 95 % CI 0.71-0.90; P < 0.001) were associated with a lower risk of NCI. Higher CRI and TIB were significantly correlated with a better performance (composite z-score) both globally and at individual cognitive domains. Our findings highlight the role of CR over clinical variables in maintaining cognitive integrity in a virologically suppressed older HIV-infected population. A lifestyle characterized by experiences of mental stimulation may help to cope aging and HIV-related neurodegeneration.

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.

Background: The aim of the study was to explore how viral resistance and antiretroviral central nervous system (CNS) penetration could impact on cognitive performance of HIV-infected patients., Methods: We performed a multicentre cross-sectional study enrolling HIV-infected patients undergoing neuropsychological testing, with a previous genotypic resistance test on plasma samples. CNS penetration-effectiveness (CPE) scores and genotypic susceptibility scores (GSS) were calculated for each regimen. A composite score (CPE-GSS) was then constructed. Factors associated with cognitive impairment were investigated by logistic regression analysis., Results: A total of 215 patients were included. Mean CPE was 7.1 (95% CI 6.9, 7.3) with 206 (95.8%) patients showing a CPE≥6. GSS correction decreased the CPE value in 21.4% (mean 6.5, 95% CI 6.3, 6.7), 26.5% (mean 6.4, 95% CI 6.1, 6.6) and 24.2% (mean 6.4, 95% CI 6.2, 6.6) of subjects using ANRS, HIVDB and REGA rules, respectively. Overall, 66 (30.7%) patients were considered cognitively impaired. No significant association could be demonstrated between CPE and cognitive impairment. However, higher GSS-CPE was associated with a lower risk of cognitive impairment (CPE-GSSANRS odds ratio 0.75, P=0.022; CPE-GSSHIVDB odds ratio 0.77, P=0.038; CPE-GSSREGA odds ratio 0.78, P=0.038). Overall, a cutoff of CPE-GSS≥5 seemed the most discriminatory according to each different interpretation system., Conclusions: GSS-corrected CPE score showed a better correlation with neurocognitive performance than the standard CPE score. These results suggest that antiretroviral drug susceptibility, besides drug CNS penetration, can play a role in the control of HIV-associated neurocognitive disorders.

Background: The aim of our study was to better understand the dynamics between cardiovascular risk factors and immunological parameters in the evolution of cognitive performance in HIV+ patients., Methods: We conducted a prospective longitudinal study, consecutively enrolling asymptomatic HIV+ subjects during routine outpatient visits at two clinical centres. At baseline and after 2 years, all patients underwent a comprehensive neuropsychological battery. Common carotid intima-media thickness (cIMT) was also measured., Results: A total of 150 patients completed the study (77% males, median age 46 years, 20% with past AIDS-defining events, 95% on cART, 88% with HIV-RNA<50 copies/ml). After a 2-year follow-up, there was no difference in the proportion of patients with cognitive impairment (32% versus 33% at baseline; P=1.00). However, a significantly worse memory performance was observed (z score mean change -0.51, sd 1.05; P=0.001). At multivariate analysis, baseline dyslipidaemia (OR 2.7, 95% CI 1.1, 7.1; P=0.037) showed a significant association with a higher risk of memory impairment at 2-year follow-up, while higher baseline CD4(+) T-cell count (OR 0.80 per 100 cells/μl higher; 95% CI 0.66, 0.97; P=0.026) was found to be a protective factor, adjusting for the presence of a memory impairment at baseline. When the analysis was restricted to patients who did not change antiretroviral therapy during the study period (n=109), baseline cIMT (OR 14.6 per 0.1 mm higher; 95% CI 1.1, 189.9; P=0.041) also emerged as an independent risk factor for memory impairment at 2-year follow-up., Conclusions: Immunological parameters and cardiovascular risk factors are independently associated with the evolution of cognitive status in HIV+ patients.

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.

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.

Background: The objective of our study was to compare two different central nervous system penetration-effectiveness (CPE) scores for the prediction of cognitive dysfunction in HIV-infected patients., Methods: We performed a cross-sectional single cohort study, consecutively enrolled during routine outpatient visits. HIV-infected subjects on antiretroviral therapy with plasma HIV RNA<50 copies/ml were included. A neuropsychological battery was administered. Each patient was classified as cognitively impaired on the basis of results obtained in age-, gender-, education- and nationality-matched healthy HIV-negative subjects. Self-reported adherence to antiviral therapy was measured on a 0-100 visual analogue scale. CPE rank was calculated for each antiretroviral regimen based on rules proposed by the CHARTER group in the 2008 original version (orCPE rank) and the 2010 revised version (revCPE rank). Neuroeffectiveness categories were analysed based on cutoffs of ≥1.5 (orCPE rank) or ≥6 (revCPE rank)., Results: A total of 101 patients were enrolled (66% male, median age 47 years, median education 13 years); mean adherence was 81%. orCPE rank ≥1.5 and revCPE rank ≥6 were observed in 85.0% and 78.2% of patients, respectively (P=0.31). Asymptomatic neurocognitive impairment (ANI) was diagnosed in 50 (49.5%) subjects. In a multivariable model, after adjusting for nationality, adherence and nadir CD4(+) T-cell count, orCPE rank did not show an association with cognitive performance (P=0.704). By contrast, patients with revCPE rank ≥6 (OR 0.32, 95% CI 0.11, 0.95; P=0.039) and adherence ≥80% (OR 0.39, 95% CI 0.15, 0.99; P=0.047) showed a decreased risk of cognitive impairment., Conclusions: A high prevalence of ANI was observed in virologically suppressed HIV-infected individuals. The revCPE rank showed improved association with neurocognitive dysfunction over the orCPE rank. Moreover, a relationship between cognitive impairment and adherence to antiretroviral therapy was found.

Objectives: To explore the combined effects of aging and human immunodeficiency virus (HIV) infection on cognitive decay., Design: Cross-sectional, single-cohort study., Setting: Institute of Clinical Infectious Diseases, Catholic University of the Sacred Heart, Rome, Italy., Participants: One hundred fifty-three asymptomatic HIV-positive (HIV+) outpatients (20% aged ≥ 60) and an age- and education-matched control population of 39 HIV-negative individuals., Measurements: A neuropsychological investigation was conducted to compare four groups of participants classified on the basis of HIV serostatus and age (<60 vs ≥ 60). The effects of age and HIV infection on neuropsychological performance were analyzed using a two-by-two factorial analysis of variance. Demographic and clinical variables associated with neuropsychological performance were identified using linear regression analysis in the HIV+ population., Results: HIV infection and aging had significant negative effects on cognitive performance, but no significant interaction was observed between these two factors. Although older HIV+ participants had worse cognitive performance, they showed no distinct cognitive pattern from younger HIV+ participants. Moreover, younger HIV+ participants' performance on memory tasks was qualitatively and quantitatively comparable with that of older HIV- participants, despite the dramatic age difference., Conclusion: Aging and HIV might be additive factors in the expression of cognitive decline. As the HIV+ population ages, routine neuropsychological examinations could help clinicians better understand and manage the expression of cognitive impairment., (© 2012, Copyright the Authors Journal compilation © 2012, The American Geriatrics Society.)

Objectives: Despite the introduction of combined antiretroviral therapy (cART), the prevalence of HIV-associated neurocognitive disorders (HANDs) remains high. Aim of the study was to investigate the potential relationship between ophthalmic artery resistance index (OARI), a marker of subclinical cerebrovascular disease, and cognitive performance., Methods: We performed a cross-sectional cohort study by consecutively enrolling HIV-infected patients during routine outpatient visits. All subjects underwent a comprehensive neuropsycological battery and ultrasonographic assessment of OARI. Patients were classified as cognitively impaired if they showed decreased cognitive function involving at least two ability domains. OARI was considered abnormal if above 0.72 at left or right side. Factors associated with cognitive performance were evaluated by linear and logistic regression analysis., Results: A total of 116 patients [78.4% males, median age 44 years (IQR 37-49), 13.8% with past AIDS-defining events, median CD4 482 cells/μL (IQR 352-690), 79.3% with HIV RNA <20 copies/mL] were enrolled. A hundred-thirteen (97.4%) subjects were on cART of which 88.5% on current regimen from one year. Fifty-four (46.6%) patients were classified as cognitively impaired. ROC curves indicated that the most discriminant left and right OARI values for predicting a mild cognitive impairment were >0.72 (AUC = 0.73, sensitivity 61.8%, specificity 81.4%, p < 0.001) and >0.71 (AUC = 0.72, sensitivity 69.1%, specificity 71.2%, p < 0.001), respectively. Multivariate analysis showed that OARI >0.72 (OR 4.7, p = 0.001) was independently associated with increased risk of cognitive impairment. Moreover, education (β = -0.18, p = 0.005), Zung depression score (β = +0.05, p = 0.021) and an abnormal OARI (β = +1.46, p = 0.002) were independently associated with an increased number of pathological performances. Evaluating separately each cognitive domain, an abnormal OARI confirmed an independent association with lower performance in attention and executive functions (p = 0.003) and in psychomotor speed (p = 0.010)., Conclusions: Increased OARI was associated with lower cognitive performance in HIV-infected patients. These findings suggest a potential role of subclinical cerebrovascular disease in the pathogenesis of HAND., (Copyright © 2012 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Introduction Raltegravir intensification is associated with an increase in 2-LTR episomal HIV DNA= circles, indicating a persistent low-level replication, in some individuals in ART with suppressed HIV RNA. We aimed at monitoring residual plasma HIV RNA and cellular HIV DNA in virologically suppressed patients switching to a raltegravir-based regimen. Materials and Methods Forty-six HIV-infected subjects on PI or NNRTI based-regimens, with plasma HIV RNA level <40 copies/mL for ≥6 months and CD4 >200 cells/µL for ≥12 months were enrolled. Thirty-four patients switched to raltegravir-based regimen (RASTA study group) and 12 continued a PI or NNRTI based-regimen (control group). Ultrasensitive HIV residual viremia and total PBMC HIV DNA were assessed at baseline (W0), 24 (W24) and 48 (W48) weeks. HIV RNA levels were determined by an ultrasensitive test derived from a commercial real time PCR (limit of detection 5 copies/ml). A real time PCR was used to quantify HIV DNA copy numbers in PBMCs. Results At W0, HIV DNA was detected in all patients while at W48 it was detectable in 82.3% of RASTA group vs 100% of controls (p=0.01). The difference between the average values of HIV DNA log10 copies/10°6 CD4 at W0 (median 3.11, IQR 2.70-3.45) and W48 (median 2.87, IQR 2.24-3.38) was statistically significant for RASTA group (p=0.035). Male gender (mean difference −0.37 log10 copies/10°6 PBMC, p=0.023) and previous PI based-ART (mean difference +0.39 log10 copies/10°6 PBMC, p=0.036) were predictive of HIV DNA level at W0. After adjusting for previous PI based-ART, male gender was the only variable independently associated with HIV DNA size at W0 (mean difference −0.326 log10 copies/10°6 PBMC, 95% CI −0.641, −0.011 p=0.043). Ultrasensitive HIV-1 RNA was detectable at W0 in 50% of RASTA group versus 66.7% of controls and at W48 in 32.4% versus 45.5%, respectively. No differences were found between HIV RNA levels at W0 and W48 within and between the two groups. Conclusions Switching to raltegravir-based regimens may be associated with a decrease of HIV reservoir, as measured by total PBMC HIV DNA. A larger sample size is required to confirm this finding. [ABSTRACT FROM AUTHOR]

Introduction According to recent evidence about boosted protease inhibitors (PIs/r)-simplified regimens, the combination of 3TC and DRV/r 800/100 mg could represent a feasible option for optimizing antiretroviral therapy (ART) in treatment-experienced HIV+ patients. Patients and Methods We retrospectively evaluated patients switching to 3TC+DRV/r, with at least six months of viral suppression, no resistance mutation to DRV or 3TC and not HBV-coinfected: incidence of ART discontinuation and of virological failure (VF: 2 consecutive HIV-RNA determinations>49 cps/mL or a single one≥1000 cps/mL) and the probability of remaining discontinuation-free during one-year follow-up (FU), as well as changes in laboratory parameters at 1, 3, 6 and 12 months were estimated. Results We included 94 patients: 74 males, mostly MSM (39.4%), with 49 years old, 9 years of HIV disease, 8 years of ART (median values). Median nadir CD4 count and zenith viral load (log10) were 194 cells/µL and 4.90, respectively. Ten patients were HCV-coinfected and 38 had at least a previous VF. Seventy-four patients were on an NRTIs-based triple regimen (mainly TDF/FTC or 3TC/ABC) whereas 14 on another PI-based dual therapy (mainly LPV/r). Incidence of treatment discontinuation was 12.4 per 100 patients-year follow-up (PYFU), but only 2 patients experienced a VF (3.5 per 100 PYFU). Mean time free from discontinuation was 5 years (95% CI 4-6), with a cumulative one-year estimated probability of staying on 3TC+DRV/r of 85.9%. At three months, a trend of increased CD4 cells count (+42 cells/µL, p 0.059) was observed, but not confirmed at later time point; an increase of total cholesterol (TC, +17mg/dL, p 0.008) and LDL (+19 mg/dL, p 0.002), and a decreased level of AST and ALT (−2 UI/L, p 0.045; −5 UI/L, p 0.009, respectively) were also detected. Total bilirubin was reduced (−0.71 mg/dL, p 0.038). At 6 and 12 months, alteration of lipid profile was similar, with also an increased TC/HDL ratio (+0.48, p=0.030, at six months) and HDL/LDL ratio (−0.04, p=0.035, at 12 months). A significant decrease in ALT levels (−6 UI/L, 0.013) and a diminishing trend for AST and total bilirubin, as well as a significant increase in renal function (GFR +4mL/min, p 0.048) were observed at 12 months. Conclusions These observations on 3TC+DRV/r-based dual therapy simplification in virologically suppressed patients show a good profile of efficacy and safety. An extended FU time is needed in order to establish the real impact of this promising therapeutic choice. [ABSTRACT FROM AUTHOR]