Efavirenz associated with cognitive disorders in otherwise asymptomatic HIV-infected patients

Despite the availability of potent antiretroviral regimens (combination antiretroviral therapy [cART]), HIV-associated neurocognitive disorders (HAND) are increasingly recognized. Our aim was to investigate the prevalence and treatment-related correlates of HAND, exploring the potential neurotoxicity of antiretrovirals on cognitive functions

Verbal list learning and memory profiles in HIV-infected adults, Alzheimer’s disease, and Parkinson’s disease: An evaluation of the “cortical hypothesis” of NeuroAIDS

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

Cardiovascular risk factors and carotid intima-media thickness are associated with lower cognitive performance in HIV-infected patients

OBJECTIVES: The aim of the study was to investigate the relationship between metabolic comorbidities, cardiovascular risk factors or common carotid intima-media thickness (cIMT) and cognitive performance in HIV-infected patients. METHODS: Asymptomatic HIV-infected subjects were consecutively enrolled during routine out-patient visits at two clinical centres. All patients underwent an extensive neuropsychological battery and assessment of metabolic comorbidities and cardiovascular risk factors. Moreover, cIMT was assessed by ultrasonography. Cognitive performance was evaluated by calculating a global cognitive impairment (GCI) score obtained by summing scores assigned to each test (0 if normal and 1 if pathological). RESULTS: A total of 245 patients (median age 46 years; 84.1% with HIV RNA < 50 copies/mL; median CD4 count 527 cells/μL) were enrolled in the study. Cardiovascular risk factors were highly prevalent in our population: the most frequent were dyslipidaemia (61.2%), cigarette smoking (54.3%) and hypertension (15.1%). cIMT was abnormal (≥ 0.9mm) in 31.8% of patients. Overall, the median GCI score was 2 [interquartile range (IQR) 1-4]; it was higher in patients with diabetes (P = 0.004), hypertension (P = 0.030) or cIMT ≥ 0.9 mm (P < 0.001). In multivariate analysis, it was confirmed that diabetes (P = 0.007) and cIMT ≥ 0.9 mm (P = 0.044) had an independent association with lower cognitive performance. In an analysis of patients on combination antiretroviral therapy (cART), abacavir use was independently associated with a better cognitive performance (P = 0.011), while no association was observed for other drugs or neuroeffectiveness score. CONCLUSIONS: Diabetes, cardiovascular risk factors and cIMT showed a strong association with lower cognitive performance, suggesting that metabolic comorbidities could play a relevant role in the pathogenesis of HIV-associated neurocognitive disorders in the recent cART era

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

Objectives: To investigate the long-term safety and efficacy of a treatment switch to dual ART with atazanavir/ritonavir+lamivudine versus continuing a standard regimen with atazanavir/ritonavir+2NRTI in virologically suppressed patients. Methods: ATLAS-M is a 96 week open-label, randomized, non-inferiority (margin -12%) trial enrolling HIV-infected adults on atazanavir/ritonavir+2NRTI, with stable HIV-RNA &lt; 50 copies/mL and CD4 counts.200 cells/mm 3 . 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

Treatment simplification to atazanavir/ritonavir+lamivudine versus maintenance of atazanavir/ritonavir+two NRTIs in virologically suppressed HIV-1-infected patients: 48 week results from a randomized trial (ATLAS-M)

none149noBackground: 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 &lt;50 copies/mL and CD4+&gt;200 cells/mm3. 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 300mg of atazanavir/ 100mg of ritonavir once daily and 300mg 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 &lt;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.mixedDi Giambenedetto, S.; Fabbiani, M.; Quiros Roldan, E.; Latini, A.; D'Ettorre, G.; Antinori, A.; Castagna, A.; Orofino, G.; Francisci, D.; Chinello, P.; Madeddu, G.; Grima, P.; Rusconi, S.; Di Pietro, M.; Mondi, A.; Ciccarelli, N.; Borghetti, A.; Focà, E.; Colafigli, M.; De Luca, A.; Cauda, R.; Baldonero, E.; Belmonti, S.; D'Avino, A.; Gagliardini, R.; Lamonica, S.; Lombardi, F.; Sidella, L.; Tamburrini, E.; Visconti, E.; Giacometti, A.; Barchiesi, F.; Castelli, P.; Cirioni, O.; Mazzocato, S.; Blanc, P.; Degli Esposti, A.; Del Pin, B.; Mariabelli, E.; Marini, S.; Poggi, A.; Amadasi, S.; Apostoli, A.; Biasi, L.; Bonito, A.; Brianese, N.; Compostella, S.; Ferraresi, A.; Motta, D.; Mughini, M.T.; Celesia, B.M.; Gussio, M.; Sofia, S.; Tana, M.; Tundo, P.; Viscoli, C.; De Hoffer, L.; Di Biagio, A.; Grignolo, S.; Parisini, A.; Schenone, E.; Taramasso, L.; Manconi, P.E.; Boccone, A.; Ortu, F.; Piano, P.; Serusi, L.; Puoti, M.; Moioli, M.C.; Rossotti, R.; Travi, G.; Ventura, F.; Galli, M.; Di Nardo Stuppino, S.; Di Cristo, V.; Giacomelli, A.; Vimercati, V.; Viale, P.; Gori, A.; Rizzardini, G.; Capetti, A.; Carenzi, L.; Mazza, F.; Meraviglia, P.; Rosa, S.; Zucchi, P.; Mineo, M.; Giuliani, M.; Pacifici, A.; Pimpinelli, F.; Solivetti, F.; Stivali, F.; Angelici, F.; Bellagamba, R.; Delle Rose, D.; Fezza, R.; Libertone, R.; Mosti, S.; Narciso, P.; Nicastri, E.; Ottou, S.; Tomassi, C.; Vlassi, C.; Zaccarelli, M.; Zoppè, F.; Vullo, V.; Altavilla, F.; Ceccarelli, G.; Fantauzzi, A.; Gebremeskel, S.; Lo Menzo, S.; Mezzaroma, I.; Tierno, F.; Petrosillo, N.; Boumis, E.; Cicalini, S.; Grilli, E.; Musso, M.; Stella, C.; Mura, M.S.; Bagella, P.; Mannazzu, M.; Soddu, V.; Caramello, P.; Carcieri, C.; Carosella, S.; Farenga, M.; Scotton, P.G.; Rossi, M.C.; Concia, E.; Corsini, F.; Gricolo, C.; Lanzafame, M.; Lattuada, E.; Leonardi, S.; Rigo, F.; Lazzarin, A.; Bigoloni, A.; Carini, E.; Nozza, S.; Spagnuolo, V.; Belfiori, B.; Malincarne, L.; Schiaroli, E.; Sfara, C.; Tosti, A.; Sacchini, D.; Ruggieri, A.; Valdatta, C.Di Giambenedetto, S.; Fabbiani, M.; Quiros Roldan, E.; Latini, A.; D'Ettorre, G.; Antinori, A.; Castagna, A.; Orofino, G.; Francisci, D.; Chinello, P.; Madeddu, G.; Grima, P.; Rusconi, S.; Di Pietro, M.; Mondi, A.; Ciccarelli, N.; Borghetti, A.; Focà, E.; Colafigli, M.; De Luca, A.; Cauda, R.; Baldonero, E.; Belmonti, S.; D'Avino, A.; Gagliardini, R.; Lamonica, S.; Lombardi, F.; Sidella, L.; Tamburrini, E.; Visconti, E.; Giacometti, A.; Barchiesi, F.; Castelli, P.; Cirioni, O.; Mazzocato, S.; Blanc, P.; Degli Esposti, A.; Del Pin, B.; Mariabelli, E.; Marini, S.; Poggi, A.; Amadasi, S.; Apostoli, A.; Biasi, L.; Bonito, A.; Brianese, N.; Compostella, S.; Ferraresi, A.; Motta, D.; Mughini, M. T.; Celesia, B. M.; Gussio, M.; Sofia, S.; Tana, M.; Tundo, P.; Viscoli, C.; De Hoffer, L.; Di Biagio, A.; Grignolo, S.; Parisini, A.; Schenone, E.; Taramasso, L.; Manconi, P. E.; Boccone, A.; Ortu, F.; Piano, P.; Serusi, L.; Puoti, M.; Moioli, M. C.; Rossotti, R.; Travi, G.; Ventura, F.; Galli, M.; Di Nardo Stuppino, S.; Di Cristo, V.; Giacomelli, A.; Vimercati, V.; Viale, P.; Gori, A.; Rizzardini, G.; Capetti, A.; Carenzi, L.; Mazza, F.; Meraviglia, P.; Rosa, S.; Zucchi, P.; Mineo, M.; Giuliani, M.; Pacifici, A.; Pimpinelli, F.; Solivetti, F.; Stivali, F.; Angelici, F.; Bellagamba, R.; Delle Rose, D.; Fezza, R.; Libertone, R.; Mosti, S.; Narciso, P.; Nicastri, E.; Ottou, S.; Tomassi, C.; Vlassi, C.; Zaccarelli, M.; Zoppè, F.; Vullo, V.; Altavilla, F.; Ceccarelli, G.; Fantauzzi, A.; Gebremeskel, S.; Lo Menzo, S.; Mezzaroma, I.; Tierno, F.; Petrosillo, N.; Boumis, E.; Cicalini, S.; Grilli, E.; Musso, M.; Stella, C.; Mura, M. S.; Bagella, P.; Mannazzu, M.; Soddu, V.; Caramello, P.; Carcieri, C.; Carosella, S.; Farenga, M.; Scotton, P. G.; Rossi, M. C.; Concia, E.; Corsini, F.; Gricolo, C.; Lanzafame, M.; Lattuada, E.; Leonardi, S.; Rigo, F.; Lazzarin, A.; Bigoloni, A.; Carini, E.; Nozza, S.; Spagnuolo, V.; Belfiori, B.; Malincarne, L.; Schiaroli, E.; Sfara, C.; Tosti, A.; Sacchini, D.; Ruggieri, A.; Valdatta, C