Suchergebnisse

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.

BackgroundHIV can spread into the central nervous system (CNS) early in the course of infection and this turns into intrathecal inflammation and neuronal damage. We aimed to investigate clinical and immunological parameters associated with elevated CSF VL in HIV‐infected ART‐naïve patients.Materials and MethodsHIV+ ART‐naïve patients underwent a comprehensive battery of neurocognitive (NC) tests and lumbar puncture (LP) for CSF HIV‐RNA detection. Plasma HIV‐RNA and peripheral T‐cell immune‐phenotypes (CD38/CD45RA/CD45R0/CD127 on CD4/CD8) were also assessed (flow cytometry). High‐CSF HIV RNA was defined as≥10000cp/mL (H‐CSF), while CSF HIV RNA<10000cp/mL characterized low VL patients (L‐CSF). Chi‐square and Mann‐Whitney tests were used. Parameters independently associated with CSF VL were explored by multivariate regression.ResultsA total of 131 patients were retrospectively enrolled. Forty‐two patients (32%) had CSF VL >10000 cp/mL.Table 1 shows the features of H‐ versus L‐CSF patients. Compared to L‐CSF patients, H‐CSF patients displayed lower current CD4+%, lower CD4/CD8 ratio and higher CD8%. No differences in NC tests performance were observed between groups (p=0.6). Regarding T‐cell immuno‐phenotypes, H‐CSF patients displayed a higher proportion of CD45R0+CD38+CD8+ (11 vs 7%, p=0.02) and lower expression of CD45RA+CD8+ % (16 vs 20%, p=0.007), in comparison to L‐CSF patients. In multivariate analysis CD45RA+CD8+ T‐cells % (OR 0.917, CI 95% 0.852–0.987, p=0.002) was associated with H‐CSF, even after adjustment for plasma VL, CD8 and CD4 count. Globally, in univariate CSF VL inversely correlated with CD45RA+CD8+ % (r=−0.223, p=0.0217) and CD127+CD4+ % (r= −0.204, p= 0.0225), while a positive association was found between CSF and plasma VL (r=0.303, p=0.0004) and CD8 % (r=0.211, p=0.016). In multivariate linear regression, in addition to positive association between plasma and CSF VL (β: 0.212, 95% CI 0.02–0.41, p=0.032), also CD45RA+CD8+ % were confirmed inversely associated to CSF VL (β: 0.21, 95% CI −0.5 to −0.002, p=0.036), adjusting for CD4/CD8 and CD4CD127 %.ConclusionsWe hereby describe a 32% prevalence of H‐CSF in a cohort of HIV+ ART‐naïve patients. Subjects with high‐CSF viral replication are mostly with higher systemic immune activation, in particular the percentage of naïve CD8 T‐cell is positively associated with CSF VL, irrespective of plasma VL. In HIV+ ART‐naïve patients, especially if featuring a hyperactivated T‐cell immune‐phenotype, lumbar puncture should be considered to further guide CNS‐targeted cART.

IntroductionEvidence from HIV‐negative cohorts suggests a link between osteoporosis and cardiovascular disease. We evaluated the presence and distribution of abdominal aortic calcifications (AAC) and its correlation with bone mineral density (BMD) and vertebral fractures (VF) in a cohort of HIV‐positive patients.Materials and MethodsIn this cross‐sectional study, 280 asymptomatic HIV‐positive patients from the SPID ("San Paolo" Infectious Diseases) cohort were submitted to lateral spine X‐ray and DXA. AAC was identified using the AAC‐8 score, which estimates the total length of calcification of the anterior and posterior aortic walls in front of vertebrae L1–L4. Low BMD was defined by T‐score or Z‐score <−1 at lumbar spine or femoral neck. VF were identified by morph‐metric analysis of X‐ray and were defined by the "spine deformity index" (SDI) ≥1 according to semiquantitative method by Genant. Associations between AAC, BMD and SDI were evaluated by univariate and multivariate logistic regression models. The relationship between the grade of AAC and SDI was evaluated by Spearman's correlation.ResultsAAC≥1 was present in 65 patients (23.2%); of these 15 patients showed moderate/severe calcifications (AAC>2). Low BMD was found in 163 patients (58.2%) and VF (SDI≥1) in 47/274 patients (17.1%). By univariate analysis, factors associated with AAC>=1 were: age (for additional 10 years older HR 3.81 [IC95% 2.64–5.51], p<0.0001) lower CD4 nadir (for additional 50 CD4 HR 0.89 [IC95% 0.82–0.97], p=0.01) AIDS‐diagnosis (HR 2.13 [IC95 % 1.11–4.08], p=0.02) and being on HAART (HR 2.75 [IC95% 1.28–5.90], p=0.009). In multivariate analysis, only age (OR 2.62, IC95% 1.72–3.99, p<0.0001) resulted significantly associated with AAC≥1. Patients with AAC≥1 had twofold increase in the risk of low BMD (HR 2.45 [IC95% 1.32–4.45], p=0.004) and VF (SDI>=1: HR 2.17 [IC95% 1.1–4.2], p=0.02) compared to patients without AAC. The grade of AAC was directly correlated with the grade of SDI (rho=0.16; p=0.008): AAC>2 determines a sixfold increase in the risk of VF (HR 6.44 [IC95% 2.21–18.79], p=0.0006). AAC≥1 predict VF independently from BMD, vitamin D status and bone turnover marker (Table 1).ConclusionsIn our HIV population, AAC resulted a strong predictor of both low BMD and VF, irrespective of factors involved in bone formation. The grade of AAC was directly correlated with the grade of VF.