Suchergebnisse

IntroductionSwitch to Stribild (STB) was non‐inferior to continuation of a non‐nucleoside reverse transcriptase inhibitor (NNRTI) with emtricitabine and tenofovir DF (FTC/TDF) at week 48 in virologically suppressed HIV adults [1]. We report the Week 48 efficacy and safety of STB versus nevirapine (NVP) or rilpivirine (RPV) with FTC/TDF in suppressed subjects.Materials and MethodsVirologically suppressed subjects on an NNRTI with FTC/TDF regimens for ≥6 months were randomized (2:1) to switch to STB versus continue their NNRTI regimen. Eligibility criteria included no documented resistance to FTC and TDF, no history of virologic failure and eGFR ≥70 mL/min. The primary endpoint was the proportion of subjects in the modified ITT population who maintained HIV‐1 RNA <50 copies(c)/mL at Week 48 by FDA snapshot algorithm (12% non‐inferiority margin). Subgroup analysis by non‐EFV NNRTI use (NVP [74]; RPV [19]; etravirine [3]) at screening was pre‐specified.ResultsThe mITT population included 433 subjects who were randomized and treated. In the non‐EFV NNRTI subgroup, 59 switched to STB; 37 continued a non‐EFV NNRTI (27 NVP, 10 RPV) with FTC/TDF. At week 48, 97% STB versus 95% non‐EFV NNRTI maintained HIV‐1 RNA <50 c/mL. No emergent resistance was detected in either group. No difference in median increases from baseline in CD4 count at week 48 (cells/µL): 25 STB versus 55 non‐EFV NNRTI (p=0.78). No discontinuation due to adverse events; no cases of proximal renal tubulopathy. As expected, there were no significant changes in the frequency of neuropsychiatric symptoms (i.e. anxiety, insomnia, dizziness, vivid dreams, weird/intense dreams, and nightmares) reported on the HIV Symptom Index at week 48 compared to baseline after switching to STB. There was a greater but non‐progressive decrease from baseline in eGFR in the STB versus non‐EFV NNRTI group; median changes (mL/min) at week 48: −9.1 versus −1.4. Switch to STB was associated with a higher treatment ease (convenience, flexibility, demand, lifestyle, understanding) score (range: −15 to 15) at week 4 (median: 14 vs 11; p=0.047) and week 24 (median: 14 vs 12.5; p=0.038).ConclusionsIn this small group of virologically suppressed subjects, switch to STB vs continuation of NVP or RPV with FTC/TDF was safe, well‐tolerated, and associated with a high rate of virologic suppression at week 48. There was more treatment ease with STB use.

IntroductionThis descriptive, non‐interventional study on HIV‐1‐infected patients treated with DRV/r in the usual clinical setting, with a single‐arm prospective observational design, collected data on utilization of darunavir/ritonavir (DRV/r) under the conditions described in marketing authorization in usual clinical practice in Italy to evaluate efficacy and safety of DRV/r‐based antiretroviral (ARV) treatment. This analysis focussed on the safety profile of DRV/r in HIV‐1 infected patients.Materials and MethodsData were analyzed from four cohorts of HIV‐1‐infected patients treated with DRV/r in the real‐world setting, including an ARV‐naïve‐DRV/r‐naïve cohort (Cohort 1), an ARV‐experienced‐DRV/r‐naïve cohort (Cohort 2) and two ARV‐DRV/r‐experienced cohorts (Cohorts 3 and 4), one of which (Cohort 3) was from the DRV/r Early Access Program. The objective of this analysis was to examine the safety data obtained in these four cohorts in patients enrolled from June 2009 to November 2011 and observed until December 2012 or DRV/r discontinuation.ResultsSafety data from 875 patients were analyzed. DRV/r‐based treatment was well tolerated, with 36.2% of patients reporting ≥1 adverse event (AE) and very few discontinuations due to study drug‐related AEs (3.0% overall). The most frequent AEs were diarrhoea (2.7%), reduced bone density (2.6%) and hypercholesterolaemia (2.1%) (Table 1). Regarding metabolic parameters, levels of liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) remained stable from baseline to the last study visit (LSV) in DRV‐experienced patients and decreased in DRV‐naïve patients. Blood glucose concentrations remained stable in all cohorts. Serum triglyceride and cholesterol concentrations remained stable in DRV‐experienced patients but increased in naïve patients, yet were still within normal range.ConclusionsIn HIV‐1‐infected patients treated with DRV/r in these settings, the tolerability profile was favourable and similar to (or better than) that reported in controlled clinical trials. These data confirm DRV/r to be a safe treatment choice in DRV/r‐experienced and naïve patients.

IntroductionThis was a descriptive non‐interventional study in HIV‐1‐infected patients treated with DRV/r conducted in the clinical setting, with a single‐arm prospective design. The primary objective was to collect data on utilization of darunavir/ritonavir (DRV/r) under the conditions described in the marketing authorization. Efficacy (measured as viral load [VL] <50 copies/mL and CD4+ cell count) was evaluated for DRV/r in combination with other antiretroviral (ARV) agents in routine clinical practice in Italy.Materials and MethodsHere we describe an analysis of effectiveness and durability data from two cohorts of DRV/r‐experienced patients with HIV‐1 infection, already receiving DRV/r according to usual clinical practice, collected prospectively from June 2009 to December 2012: Cohort 1, data from patients from the DRV/r Early Access Program (TMC114‐C226 study; N=235 patients) and Cohort 2, a separate cohort of ARV‐DRV/r‐experienced patients (N=407 patients), treated with DRV/r in the market. Patient characteristics are shown in Table 1.ResultsThe median length of DRV/r exposure during the study was 925 days (interquartile range [IQR] 692–1006) in Cohort 1, and 581 (IQR 508–734) days in Cohort 2. Of those patients that completed the study, 94% and 87% of patients were virologically suppressed in Cohort 1 and 2, respectively, at last study visit (LSV). As expected, the virological suppression rate was higher in patients with baseline VL <50 copies/mL (Table 2). Mean CD4+ cell counts improved from baseline to LSV in both cohorts (Cohort 1: +54 cells/µL [95% CI 31, 77] and Cohort 2: +59 cells/µL [95% CI 44, 73]). High persistence rates were seen in both cohorts, with 75.3% of patients in Cohort 1 and 82.6% in Cohort 2 remaining on treatment at LSV; very few patients discontinued due to virologic failure (Table 1). Other reasons for study discontinuation are shown in Table 1. Very few patients changed DRV/r dosing during the study, 15 from 1200 to 800 mg o.d.ConclusionsIn patients already treated with DRV/r, DRV/r‐based ARV treatment provided effective viral suppression with long‐lasting durability, low virological response failure, low discontinuation rates and good tolerability. These data confirm DRV/r to be an effective treatment choice in previously treated patients.

IntroductionIn clinical trials, toxicity leading to discontinuation of tenofovir (TDF) is a rare occurrence (3% by two years)[1, 2]; however, in clinical practice it seems to be higher. Previous studies suggested that TDF toxicity is higher when it is co‐administered with ritonavir‐boosted protease inhibitors (PI/r)[3, 4]. The aim of this study is to assess the rate of TDF discontinuations in clinical practice and to explore associated factors.MethodsAll previously antiretroviral‐naïve patients initiating a TDF‐containing regimen were selected from the ICONA cohort, unless they were positive for hepatitis B. The primary outcome was TDF discontinuation (>30 days) regardless of the reason, the secondary was TDF discontinuation due to toxicity. All analyses were repeated for the isolated stop of TDF (no stop of associated drugs). The main reason for discontinuation as reported by the treating physicians was used to classify stops. Kaplan–Meier (KM) analysis and Cox proportional hazards model were used.ResultsA total of 3,303 naïve patients were enrolled: 674 (20.4%) were female, the median age was 38 years (32–45), 55% were on PI/r‐based regimen and 45% on NNRTI; 80% of calculated estimated glomerular filtration rates (eGFR) were >90 ml/min. The probability of discontinuation of TDF regardless of the reason was 10% (95% CI 8–11) at two years, 20% by eight years. The causes of discontinuation were: toxicity (33%), failure (10%), non‐adherence (21%), simplification (16%) and other/unknown causes (20%). The five‐year KM estimates in the PI/r vs. not PI/r groups were 23% vs. 10%, respectively (log‐rank p=0.0001), for the outcome of stopping regardless of the reason, and 8% vs. 4% (p=0.18) for discontinuation due to toxicity. In a multivariable Cox model, PI/r use and lower body weight were associated with increased risk of discontinuing TDF regardless of the reason; lower eGFR at baseline was associated with TDF discontinuation for toxicity and PI/r use was associated with isolated stop of TDF (Figure). No differences in rates of TDF discontinuations between PIs were found.ConclusionIn our cohort, the observed frequency of TDF discontinuations was low although higher than estimated in clinical trials (10% by two years). Co‐administration of TDF with PI/r was associated with an increased rate of TDF discontinuations. This finding should guide further investigations of the mechanism that may have led to discontinuation of TDF in patients using PI/r.

IntroductionIn previous studies, protease inhibitor (PI) monotherapy has shown trends for higher low‐level elevations in HIV‐1 RNA compared to triple therapy, but no increase in the risk of drug resistance.MethodsA total of 273 patients with HIV‐1 RNA <50 copies/mL for over 24 weeks on current antiretrovirals switched to DRV/r (darunavir/ritonavir) 800/100 mg once‐daily, either as monotherapy (n=137) or with 2NRTIs (nucleoside reverse‐transcriptase inhibitors) (n=136), after a 4 week run‐in phase with DRV/r + 2NRTI. Treatment failure was defined as HIV‐1 RNA levels above 50 copies/mL (FDA Snapshot method) by Week 48, or switches off study treatment. Patients with elevations in HIV‐1 RNA on DRV/r monotherapy could be re‐intensified with NRTIs. The trial had 80% power to show non‐inferiority for the monotherapy arm (delta = − 12%).ResultsPatients were 83% male and 87% Caucasian, with mean age 42 years; 10% were HCV antibody positive. In the DRV/r monotherapy arm, there were more patients with nadir CD4 count below 200 cells/µL (30% versus 22%). In the primary efficacy analysis, HIV‐1 RNA <50 copies/mL by Week 48 (intent‐to‐treat (ITT)) was 118/137 (86.1%) in the DRV/r monotherapy arm versus 129/136 (94.9%) in the triple therapy arm; DRV/r monotherapy did not show non‐inferiority versus triple therapy in the primary analysis (difference=− 8.7%, 95% CI −15.5 to −1.8%). In the multivariate analysis, the main predictor of treatment failure was nadir CD4 count. For patients with nadir CD4 counts <200 cells/µL, HIV‐1 RNA suppression rates at Week 48 were 27/41 (66%) in the DRV/r monotherapy arm and 29/30 (97%) in the triple therapy arm; for patients with CD4 nadir at least 200 cells/µL, HIV‐1 RNA suppression rates were 91/96 (95%) in the DRV/r monotherapy arm and 100/106 (94%) in the triple therapy arm. In the overall population, by a switch included analysis, efficacy was 92.0% versus 96.3%, showing non‐inferiority (difference=− 4.3%, 95% CI=−9.7 to +1.2%). No treatment‐emergent primary PI mutations were detected in three patients with sustained elevations in HIV‐1 RNA at least 400 copies/mL (two on PI monotherapy, one on triple therapy). CD4 counts remained stable during the trial in both arms.ConclusionsIn this study for patients with HIV‐1 RNA < 50 copies/mL at baseline, switching to DRV/r monotherapy showed lower efficacy versus triple antiretroviral therapy at Week 48 in the primary switch equals failure analysis (86% versus 95%). However, this lower efficacy was seen mainly in patients with CD4 nadir levels below 200 cells/µL. There was no development of PI resistance.

IntroductionSeveral genetic single nucleotide polymorphisms (SNPs) in biotransformation enzymes (CYP3A4, CYP3A5) or transporter proteins (multidrug resistance MDR1 gene product, P‐gp) are involved in PI metabolism so that PI pharmacokinetics is characterized by a large inter‐individual variability. The aim of this study was: (i) to develop an in‐house PCR/direct sequencing, based on DNA purification of full‐length CYP3A4 and CYP3A5 genes (SNPs) and MDR1 C3435T variant; (ii) to investigate association of CYP3A4 and CYP3A5 reported or unreported genetic polymorphisms and MDR1‐C3435T (CC homozygote, CT heterozygote, TT homozygote) with clinical outcome of HIV‐1 infected subjects treated with PI.MethodsOverall, 39 HIV‐1 infected patients receiving boosted Lopinavir (LPV/r) monotherapy after virological suppression were genotyped and analyzed through PCR and direct sequencing of full‐length CYP3A4 and CYP3A5 gene sequences [1] and MDR1 gene (C3435T). CD4+T‐cell counts and plasma viral load were analyzed before and after LPV/r initiation; LPV/r therapeutic drug monitoring (TDM) was determined at 12‐hours.ResultsLPV/r TDM (ng/ml) did not show significant differences among CYP3A4 or CYP3A5 SNPs, although a mean lower level of LPV/r was associated with detection of several SNPs: CYP3A5*3 rs776746; CYP3A5 rs28365088, CYP3A5 rs15524, CYP3A4 rs2687116, and a not already described polymorphism CYP3A4 nt20338. In follow‐up analysis, <90% adherence was the main factor associated with virological failure of LPV/r monotherapy (83.3% of failure vs 34.4%, p<0.001 at log‐rank test). Adjusting for adherence, the detection of a single CYP3A5*3 rs776746 and CYP3A5 rs15524 SNPs was associated with higher probability of LPV/r monotherapy failure (p<0.01), and in general, detection of any CYP3A5 SNP was associated with failure (26.2% vs 58.3%, p=0.067). No‐association with detection of any CYP3A4 SNPs was found. MDR1 TT variants showed significant lower frequency of treatment failure (0.0% vs 47.7%, p=0.026), since non‐TT homozygote patient failed LPV/r monotherapy.ConclusionsEfficacy of PI monotherapy is strongly dependent from patient adherence, but, in adherent patients, genetic factors, such as CYP3A5 and MDR1‐C3435T gene variants, may affect the response to treatment, though their role, as well of other genetic variants, need further investigation.

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.

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

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.

IntroductionDiagnosis of HIV infection during early stages is mandatory to catch up with the challenge of limiting HIV viral replication and reservoirs formation, as well as decreasing HIV transmissions by immediate cART initiation.ObjectivesAims were to describe (a) virological characteristics of AHI identified, (b) epidemiological and clinical factors associated with being diagnosed with AHI.MethodsCross‐sectional, retrospective study. All individuals diagnosed with AHI according to Fiebig's staging between Jan 2013 and Mar 2014 at the INMI "L. Spallanzani" were included. Serum samples reactive to a fourth generation HIV‐1/2 assay (Architect HIV Ag/Ab Combo, Abbott) were retested with another fourth generation assay (VIDAS DUO HIV Ultra, Biomérieux) and underwent confirmation with HIV‐1 WB (New Lav I Bio‐Rad) and/or with Geenius confirmatory assay (Bio‐Rad). WHO criteria (two env products reactivity) were used to establish positivity of confirmatory assays. In case of clinically suspected AHI, HIV‐1 RNA (Real time, Abbott) and p24 assay (VIDAS HIV P24 Bio‐Rad) were also performed. Avidity test was carried out, on confirmed positive samples lacking p31 reactivity, to discriminate between recent (true Fiebig V phase) and late infections; to avoid possible misclassifications, clinical data were also used. Demographic, epidemiological, clinical and laboratory data are routinely, and anonymously recorded in the SENDIH and SIREA studies.ResultsDuring the study period, we observed 483 newly HIV diagnosed individuals, of whom 40 were identified as AHI (8.3%). Fiebig classification showed: 7 stage II/III, 13 stage IV, 20 stage V. Demographic, epidemiological, and clinical characteristics of patients are shown in the Table. Overall, the study population had a median S/Co ratio at fourth generation EIA (Architect) of 49.50 (IQR, 23.54–98.05): values were significantly lower in Fiebig II‐IV than in Fiebig V (38.68 [IQR, 20.08–54.84] vs 75.72 [IQR, 42.66–249.80], p=0.01). Overall, median HIV‐1 RNA was 5.44 log copies/mL (IQR, 4.29–6.18) and the value observed in Fiebig phase II‐IV was higher than that found in Fiebig stage V (6.10 [IQR, 5.49–7.00] vs 4.69 [3.71–5.44], p<0.001). Median CD4+ cell count was 596/mmc (IQR, 410–737). cART was started in 26 patients: TDF/FTC/DRV/r/RAL=18; TDF/FTC/DRV/r=2; TDF/FTC/ATV/r=2; TDF+FTC+EFV=2; TDF/FTC/RAL=1; DRV/r+RAL=1.ConclusionsIntegration of careful epidemiological investigation, partner notification, and technical advances in virological testing are key elements in AHI case‐finding. Significant differences were found between Fiebig stages II–IV and Fiebig V with regard to virological exams.

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.

IntroductionHuman papillomavirus (HPV) is responsible for 85% of anal cancers. Recently, anal cancer incidence has been increasing, particularly in men who have sex with men (MSM). Cytology may be a useful tool for the detection of anal precancerous lesions. We assessed the prevalence and determinants of anal HPV infection and cytologic abnormalities among HIV‐infected and ‐uninfected MSM.Materials and MethodsMSM ≥18‐year‐old attending an STI clinic in Rome (Italy) were enrolled. Anal cytologic samples were collected in PreservCyt (Hologic) using a Dacron swab. The Linear Array HPV Genotyping Test (Roche Diagnostics) was used for the detection and genotyping of 37 mucosal HPV types. Liquid‐based cytological slides were obtained using a ThinPrep2000 processor (Hologic). The morphology of the anal pap‐test was classified following the Bethesda 2001 guidelines.ResultsWe enrolled 180 HIV‐infected (median age 41 years, IQR 33–47) and 438 HIV‐uninfected MSM (median age 32 years, IQR: 27–39). Most of the individuals were Caucasian (92.2% and 97.0%, respectively). HPV prevalence, both overall (93.3% vs 72.4%, p<.001) and by high‐risk (HR) HPV types (80.5% vs 56.0%, p<.001), was significantly higher among HIV‐infected than HIV‐uninfected individuals. HPV‐multiple infections were evidenced in 48.2% of the HIV‐uninfected and 76.1% of the HIV‐infected MSM (p<.001). HPV16 was the most prevalent genotype in both groups (23.3% in HIV‐positive and 17.6% in HIV‐negative MSM). HPV6 and 84 were the most frequent low‐risk types in both cohorts. Anal cytologic abnormalities were found in a significantly higher proportion of HIV‐infected MSM (46.1% vs 27.9%, p<.001). H‐SILs (high‐grade squamous intraepithelial lesions) were exclusively observed among the HIV‐infected individuals, although at a low prevalence (1.2%).ConclusionsA high prevalence of anal HPV infection and cytologic abnormalities was evidenced in both populations. Nonetheless, HIV‐infected MSM showed a significantly higher rate of HPV infection and abnormal cytology, confirming that HIV‐1 infection poses a significant risk for anal HPV infection as well as for anal cellular abnormalities. Screening for anal cancer, which is currently the most frequent non‐AIDS‐defining cancer in HIV‐positive MSM, should be considered for this population. Moreover, vaccination strategies for the prevention of HPV infection should be taken into account.

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

IntroductionSexually transmitted diseases (STDs) data collected in HIV+ patients could be used as indicator of risky sexual behaviour possibly linked to HIV transmission. We described the STDs incidence over time and identified higher incidence factors.MethodologyAll patients in the ICONA Foundation Study enrolled after 1998 were included. STDs considered: any‐stage syphilis, human papilloma virus (HPV) diseases, gonococcal and non‐gonococcal urethritis, herpes simplex virus (HSV) genital ulcers, vaginitis and acute hepatitis B virus (HBV), hepatitis A virus (HAV), and hepatitis C virus (HCV) infections (only for non‐IVDU (intravenous drug user) patients). STDs incidence rate (IR): number of STDs divided by person years of follow‐up (PYFU). Calendar periods: 1998–2002, 2003–2007 and 2008–2012. Predictors of STDs occurrence were identified using Poisson regression and sandwich estimates for the standard errors were used for multiple STD events.ResultsData of 9,168 patients were analyzed (median age 37.3 (SD=9.3), 74% male, 30% MSM). Over 46,736 PYFU, 996 episodes of STDs were observed (crude IR 17.3/1,000 PYFU). Median (IQR) CD4/mmc and HIV‐RNA/mL at STD: 433 (251–600) and 10,900 (200–63,000). Highest crude IRs were observed for any‐stage syphilis (3.95, 95% CI 3.59–4.35), HPV diseases (1.96, 1.71–2.24) and acute hepatitis (1.72, 1.49–1.99). At multivariable analysis (variables of adjustment shown in Figure 1), age (IRR 0.82 per 10 years younger, 95% CI 0.77–0.89), MSM contacts (IRR 3.03, 95% CI 2.52–3.64 vs heterosexual) and calendar period (IRR 1.67, 95% CI 1.42–1.96, comparing 2008–2012 with 1998–2002) significantly increased the risk of acquiring STDs. Moreover, having a HIV‐RNA >50 c/mL (IRR 1.44, 95% CI 1.19–1.74 vs HIV‐RNA <50 c/mL) and current CD4+ cell count <100/mmc (IRR 4.66, 95% CI 3.69–5.89, p<0.001 vs CD4+ cell count >500) showed an increased risk of STDs. Being on ARV treatment significantly reduced the risk of developing an STD (IRR 0.37, 95% CI 0.32–0.43) compared to ART‐naïve people, even in the situation of temporary interruption of treatment (IRR 0.51, 95% CI 0.39–0.43) (see Figure 1).ConclusionsThe overall incidence of STDs has been increasing in the recent years. Interventions to prevent STDs and potential further spread of HIV infection should target the recently HIV diagnosed, the young population and MSM. Being on ARV treatment (potentially an indicator of whether a person is regularly seen for care) seems to reduce the risk of acquiring STDs independently of its viro‐immunological effect.