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IntroductionChronic liver disease leads to neurocognitive impairment (NCI) and more advanced liver fibrosis is associated with greater deficits. Further, cognitive performances do not differ significantly among patients affected by diverse types of chronic liver diseases. Thus, it would be useful to have a clinical tool associated with early cognitive change applicable to the HIV‐infected population with high HCV prevalence. Aim of the analysis was to assess the association between NCI and aspartate aminotransferase‐platelet ratio index (APRI) or Fibrosis‐4, which are non‐invasive scores used to assess liver fibrosis.Materials and MethodsSingle‐centre, retrospective, cross‐sectional analysis of cART‐treated HIV‐infected patients undergoing neuropsychological assessment (NPA) by a set of 14 standardized and comprehensive tests on five different domains: concentration and speed of mental processing; mental flexibility; memory, fine motor functioning; visual‐spatial and constructional abilities. NPA obtained from the same patient were included, if collected while receiving different cART. Patients were classified as having NCI, if they scored >1 SD below the normative mean in at least two tests, or below >2 SD in one test. HIV‐associated neurocognitive disorders (HAND) were classified according to Frascati's criteria, controlling for confounding comorbidities. Univariable analysis and multivariable logistic regression models were carried out.ResultsA total of 556 HIV‐infected cART‐treated patients from 2006 to 2013 were included: male 78%; IVDUs 14%; CDC stage C 31%; median CD4 nadir 200/mm3; median current CD4 501/mm3; undetectable HIV‐RNA in 368 (67%); and HCV‐positivity in 150 (29%). Frequency among score levels was for FIB‐4: min‐1.44=404 (73%), 1.45–3.25=118 (21%), 3.26‐max=28 (5%); for APRI: min‐0.5=414 (75%), 0.5–1.5=112 (20%), 1.5‐max=24 (4%). Median FIB‐4 and APRI were 0.98 and 0.27 in HIV+/HCV‐ and 1.40 and 0.50 in HIV+/HCV+ individuals, respectively. HAND was found in 176 (32%): 91 ANI, 73 MND, 12 HAD. Association of variables with NCI are shown in Table 1.ConclusionsIn this large population, HAND was not associated with commonly used non‐invasive liver fibrosis scores. As aetiology of cognitive dysfunction in HIV mono‐ and HCV co‐infected patients is multifactorial and partially unknown, our results support the hypothesis of a direct or indirect effect on cognitive function of the viruses, rather than the consequence of alterations residing outside the brain.

IntroductionPI/r monotherapy has been suggested as an attainable maintenance strategy in patients achieving stable HIV suppression in plasma. The objective of trial was to compare the virological outcome of two different PI/r QD monotherapy strategies (LPV/r or DRV/r) with maintaining a triple PI/r‐based ARV regimen.Material and MethodsPhase III, open‐label, non‐inferiority (−12% margin), randomized trial of HIV adults with HIV‐RNA <50 cp/mL for at least 48 weeks while on PI/r‐based cART, CD4 nadir >100 cell/mm3, without previous PIs virological failure. Eligible patients were randomized to continue PI/r+2NRTIs (Arm A), to switch to LPV/r 800/200 mg QD monotherapy (Arm B), or to switch to DRV/r 800/100 mg QD monotherapy (Arm C). Primary endpoint was proportion of patients with plasma HIV‐1 RNA <50 cp/mL (TLOVR) at 48w by intent to treat (ITT) analysis (missing/re‐induction=failure). FDA snapshot and ITT switch‐included analysis (ITT‐SI) were also used. In ITT‐SI, patients who had <50 copies/mL at 96w were counted as successes even if they had confirmed HIV‐RNA elevations and had subsequently successfully intensified by NRTI.ResultsDue to slow recruitment, only 103 patients were included. No differences were observed between the three arms with respect to gender, age, HIV transmission, CD4 nadir and at screening. At randomization, 61 patients were receiving TDF/FTC (60%), 19 ZDV/3TC (18%), 8 ABV/3TC (8%), 75 LPV/r (73%), 13 ATV/r (13%), 4 DRV/r (4%). Differences in proportion of virological success by groups using Arm A as comparator according to FDA TLOVR were reported in Figure 1. Similar results were obtained by Snapshot analysis. Of 14 patients with virological failure, 8 patients restarted triple therapy with 2NRTI and 7/8 regained a VL <50 cp/mL over time. According to ITT‐SI analysis, 96 week differences [95% CI] were −5.7 [−29.6; +18.2] in Arm B, and +19.6 [−1.6; +40.8] in Arm C. A GRT was performed in 6/14 patients (one not amplifiable; four without mutations; one showed E138A).ConclusionsCompared to maintaining a PI/r‐based triple ARV regimen, LPV/r QD monotherapy tended to have higher rate of virological failure and of discontinuation due to adverse event. In contrast, the response rate at week 96 during DRV/r QD mono‐therapy was non‐inferior to that of triple PI/r‐based ARV therapy. A re‐induction with 2NRTI was adequate to obtain an undetectable viremia in most of patients with virological failure.

IntroductionCentral nervous system (CNS) penetration‐effectiveness (CPE) rank was proposed in 2008 as an estimate of penetration of ARV regimen into the CNS, and validated as predictor of CSF HIV‐1 replication. Results on predictive role of CPE on neurocognitive and clinical outcome were conflicting.Materials and MethodsRetrospective, cross‐sectional analysis of neurocognitive profile in HIV‐infected cART‐treated patients. All patients underwent neuropsychological (NP) assessment by standardized battery of 14 tests on 5 different domains. People were classified as having NCI if they scored >1 standard deviation (SD) below the normal mean in at least two tests, or >2 SD below in one test. Linear and logistic regression analyses were fitted using as outcome Npz8 and impaired/not impaired respectively.ResultsA total of 660 HIV‐infected cART‐treated individuals from 2009 to 2014, contributing a total of 1003 tests (mean age 49 (IQR 43–56), male 82%; median current CD4 586/mm3; 18% HCV infected; HIV‐RNA <40 cp/mL in 84%). Current ARV regimen was 2NRTIs+1NNRTI 50.3%, 2NRTI+1PI/r in 32.6%, NRTI sparing in 11.1%. Mean CPE of current regimens was 6.6 (95% CI 6.5–6.7). As per test multivariable analysis, higher CPE values were associated to poor NP tasks (Beta=−0,09; 95% CI −0,14 −0,03; p=0.002 at multivariable linear regression). The association between higher CPE and increased NCI risk was confirmed at multivariable logistic regression, with a 1.24‐fold risk of NCI occurrence for each point increase of CPE of current regimen at the time of NP testing (see Table 1). In a sensitivity analysis performed only on patients at the first NP test, the association between higher CPE and poor NP tasks and enhanced NCI risk was only marginally confirmed (Beta=−0,05; [−0,12–0,02]; p=0,19; OR 1,13 [0,95–1,34]; p=0.17). Older age, longer time from HIV diagnosis, current CD4 count <350 cell/mm3 and lower education level were all associated to an increased risk of NCI.ConclusionsIn our analysis, higher CPE rank is associated to poorly performing at NP tasking. Even if selection bias could not be excluded due to retrospective cross‐sectional design, these results fitted with the direct correlation between high CPE and HIV dementia recently recorded in a large observational database. We think that CPE use to guide ART in patients neurocognitively impaired should be revised.

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

BackgroundTo assess efficacy and safety of treatment simplification to co‐formulated Rilpivirine/Emtricitabine/Tenofovir (RPV/FTC/TDF) in virologically suppressed patients.Materials and MethodsEndpoints of the analysis were: (a) treatment discontinuation of RPV/FTC/TDF for any reasons and (b) occurrence of virological failure (VF) defined as confirmed HIV‐RNA >50 cp/mL).ResultsOverall, 508 patients from five Italian reference centres were included: male gender 71.9%; median age 47 years (IQR 40–52); IVDU as HIV risk 17.7%; HCV‐AB positive 23.4%; CDC‐C stage 17.5%; median CD4 cells/µL at switch 655 (IQR: 487–843); median number of previous regimens three (IQR 2–7). In a median follow‐up of 196 days (IQR: 84–287), 31 patients discontinued RPV/FTC/TDF (virological failure n=5, hypersensitivity reaction n=2, GI‐toxicity n=6, liver toxicity n=1, CNS‐toxicity n=4, kidney toxicity n=5, patient's decision/lost in follow‐up n=10). Moreover, VF occurred in eight patients (five discontinued regimen, while three remained on RPV/FTC/TDF). At survival analysis, the probabilities of treatment discontinuation or VF were 5.5% and 1.2% at 6 months, 13.2% and 2.8% at 12 months, respectively (Figure 1). At adjusted Cox model, factors associated with discontinuation were: <200 CD4 cells/µL at switch (HR 5.3, 95% CI 1.1–25.9, p=0.038), number of pre‐switch regimens (for each extra regimen: HR 1.05, 95% CI 1.01–1.10, p=0.024), male gender (HR 0.4, 95% CI 0.2–0.9, p=0.032). Only the number of pre‐switch regimens was associated with VF (HR 1.13, 95% CI 1.06–1.21, p=0.001). Type of pre‐switch regimen was not associated with discontinuation or failure, but no VF was observed if switching from co‐formulated Efavirenz/FTC/TDF or from Raltegravir containing regimens. Switching to RPV/FTC/TDF led to significant improvement in fasting lipids levels: the decrease in cholesterol, LDL and triglycerides was observed switching from any regimen, but was more marked from boosted PI. In contrast, a moderate increase in transaminase (switching from all regimens except NNRTI‐containing) and creatinine (except from TDF‐containing regimens) were observed.ConclusionsOur data suggest that switching to RPV/FTC/TDF in virologically suppressed patients could be a good strategy with low risk of virological failure or treatment discontinuation; the switch is also associated with significant improvement in lipid profile.

IntroductionReduced bone mass density (BMD) is a frequent observation in HIV‐infected persons. Relationship between body mass index (BMI), weight, height and BMD was reported for many populations. In particular, BMI has been found to be inversely related to the risk of osteoporosis.MethodsThis is a cross‐sectional, monocentric study where all HIV‐infected patients referred to first DXA scan in clinical routine during 2010–2013 were included. Osteopenia and osteoporosis were defined by T‐ score <−1 and <−2.5, respectively. Patients were categorized according to WHO BMI classification: underweight <18.5 kg/m2; normal weight 18.5–24.9 kg/m2; over weight 25–29.9 kg/m2; obese >30 kg/m2. Statistical analysis was carried using logistic regression.ResultsA total of 918 patients were included: median age 49 years (IQR, 44–55); 59.4% male; 93% Caucasian. Median anthrometric characteristics were: 68 kg (IQR, 59–78); 1.7 m (IQR, 1.6–1.75); 23.5 kg/m2 (IQR, 21.4–26.2). Underweight was found in 5%, normal weight in 61%, overweight in 26% and obesity in 8% of patients. According to T‐scores, 110 (11.2%) patients were osteoporotic and 502 (54.7%) had osteopenia. In the femoral neck area, the prevalence of osteoporosis was slightly lower (5.7%) than lumbar spine site (9.2%). Agreements between sites of T‐scores for the diagnosis of osteoporosis were 26 and 172 and 346 for osteopenia and normal BMD values, respectively. T‐scores at femoral neck or lumbar spine positively correlated with BMI (p<0.001) (Figure 1). Among predictors of osteopenia/osteoporosis, univariable analysis showed: older age (p<0.0001); lower weight (p<0.0001); increasing height (p<0.002). Patients underweight had a higher risk of osteopenia (p=0.02) as well as of osteoporosis (p=0.003). Patients with BMI above normal had a reduced risk of low BMD (osteopenia p<0.0001; osteoporosis p<0.03). Controlling for calendar year, gender, ethnicity, and age, BMI was confirmed as risk factor if below normal (AdjOR of osteopenia 2.42 [95% CI 1.16–5.07] p=0.02; AdjOR of osteoporosis 3.22 [95% CI 1.60–6.49] p=0.001).ConclusionsOur findings indicate that almost 66% of HIV‐infected patients have subnormal bone mass. Further, as in other patient populations, in the HIV infection also low BMI is an important risk factor for osteopenia/osteoporosis. This finding highlights the compelling need for standardized screening actions, particularly in patients weighting below normal.

BackgroundTo assess the role of drugs used in dual therapy (DT), as cART simplification, over the risk of treatment failure.Materials and MethodsPatients starting DT regimen composed by a boosted protease inhibitor (PI/r): darunavir (DRV/r), lopinavir (LPVr) or atazanavir (ATV/r) plus a second drug: raltegravir (RAL), maraviroc (MRV) etravirine (ETR), lamivudine (3TC) or tenofovir (TDF), this one generally used in HBV co‐infected patients, were included. The effect of each drug as well as other clinical and virological cofactors over treatment failure was assessed using survival analysis.ResultsOverall, 480 patients from six reference Italian centres were included: all switched to DT with HIV‐RNA <500 cp/µL, 376 of them at <50 cp/µL. Patients who switched at <50 cp/µL showed a significant lower risk of treatment failure (13.3% versus 23.3% at 1 year and 28.0% versus 44.6% at 3 years, p=0.005), thus the analysis was focused on this subgroup. Among the patients who switched at <50 cp/µL, the proportion of drug used in DT was: DRV/r 63.0%, RAL 53.7%, ETR 19.4%, ATV/r 18.4%, MRV 17.3%, LPV/r 12.8%, TDF 6.4% and 3TC 5.9%; DRV/r‐RAL was the most widely used combination: 32.5%. Treatment failure was observed in 78 patients, of whom 38 virological and 35 for toxicity/intolerance, one patient died during follow‐up and four patients interrupted for personal decision with undetectable HIV‐RNA. At Cox Model, adjusted by gender, age, non‐Italian origin, AIDS diagnosis, time on cART, number of regimens, CD4 nadir, baseline CD4, all the drugs had a positive effect on probability of failure (Figure), however the effect was significant for DRV/r (HR:0.21, 95% CI 0.07–0.59, p=0.03), ATV/r (0.30, 0.09–0.97, p=0.044) and RAL (0.37, 0.15–0.93, p=0.034); higher CD4 count at baseline was also associated with lower risk of failure while number of previous regimens with a higher risk. Moreover, ATV/r was found significant associated with significant higher risk of failure by toxicity (as well as LPV/r) but lower risk of virological failure, while both 3TC and RAL with significant lower risk of toxicity.ConclusionsOur analysis suggest that using PI/r‐based DL is highly effective if switching from HIV‐RNA <50 cp/µL; DL should be used with caution in patients with low CD4 count and longer history of treatment; DRV/r is the best compromise among PI/r, ATV/r is effective but is associate with frequent interruption by toxicity; RAL showed high tolerability so that its use is related to the lowest risk of failure as second drug.