Shift of prevaleces and selected characteristics of HIV-1 related Neurologic disrorders in HAART era: data from Italian Register Investigative Neuro_AIDS (IRINA).

This study involved evaluation of the prevalence, clinical characteristics, and relationship with antiretroviral therapy in newly registered HIV-1-related neurologic diseases in Italy

Caratteristiche e sopravvivenza delle patologie neurologiche in HIV durante l’era della HAART: Dati del registro Italiano NeuroAIDS

Valutare prevalenza, caratteristiche cliniche, relazione con la HAART, sopravvivenza, di patologie neurologiche HIV-relate in epoca HAART

Clinical epidemiology and survival of progressive multifocal leukoencephalopathy in the era of highly active antiretroviral therapy : data from the Italian Registry Investigative Neuro AIDS (IRINA)

Human immunodeficiency virus (HIV)-associated progressive multifocal leukoencephalopathy (PML) remains a relevant clinical problem even in the era of highly active antiretroviral therapy (HAART). Aims of the study were to analyze clinical and treatment-related features and the survival probability of PML patients observed within the Italian Registry Investigative Neuro AIDS (IRINA) during a 29-month period of HAART. Intravenous drug use, the presence of focal signs, and the involvement of white matter at neuroradiology increased the risk of having PML. A reduced probability of PML was observed when meningeal signs were reported. Patients starting HAART at PML diagnosis and previously naive for antiretrovirals showed significantly higher 1-year probability of survival (.58), compared to those continuing HAART (.24), or never receiving HAART (.00). Higher CD4 cell count were associated with a higher survival probability (.45). At multivariate analysis, a younger age, higher CD4, starting HAART at PML diagnosis, the absence of previous acquired immunodeficiency syndrome (AIDS)-defining events, and the absence of a severe neurologic impairment were all associated with a reduced hazard of death. The use of cidofovir showed a trend towards a reduced risk of death

Prevalence of acquired resistance mutations in a large cohort of perinatally infected HIV-1 patients

Data of drug resistance mutations (DRMs) within the Italian vertically infected population are scarce. The aim of the present work was to assess the prevalence of DRMs in this setting. We retrospectively analysed HIV-1 pol sequences of vertically infected patients obtained from the Italian Antiviral Response Cohort Analysis (ARCA) database (https://www.dbarca.net/). Our queries were restricted to adults. DRMs were interpreted using the Stanford HIVDB resistance interpretation algorithm (https://hivdb.stanford.edu/hivdb/by-mutations/). Any modification of antiretroviral therapy after initiation was considered a change in the therapeutic regimen. Data from a total of 94 patients were analysed (Fig. 1). Patient clinical characteristics are summarized in Table 1. The population was exposed to a median of five different antiretroviral regimens (range, 1–35 regimens). Data about the ongoing antiretroviral regimen were recovered for 73 patients (78%). Fourteen (15%) had no DRMs. At least one major DRM to nucleos(t)ide reverse transcriptase inhibitors (N(t)RTIs) was found in 74 cases (79%), to nonnucleoside reverse transcriptase inhibitors (NNRTIs) in 61 (65%) cases, to protease inhibitors (PIs) in 33 cases (35%) and to integrase strand transfer inhibitor (INSTIs) in 7 (7%)

Evolution of transmitted HIV-1 drug resistance and viral subtypes circulation in Italy from 2006 to 2016

Objectives: The aim was to evaluate the evolution of transmitted HIV-1 drug resistance (TDR) prevalence in antiretroviral therapy (ART)-naïve patients from 2006 to 2016. Methods: HIV-1 sequences were retrieved from the Antiviral Response Cohort Analysis (ARCA) database and TDR was defined as detection of at least one mutation from the World Health Organization (WHO) surveillance list. Results: We included protease/reverse transcriptase sequences from 3573 patients; 455 had also integrase sequences. Overall, 68.1% of the patients were Italian, the median CD4 count was 348 cells/μL [interquartile range (IQR) 169–521 cells/μL], and the median viral load was 4.7 log 10 HIV-1 RNA copies/mL (IQR 4.1–5.3 log 10 copies/mL). TDR was detected in 10.3% of patients: 6% carried mutations to nucleos(t)ide reverse transcriptase inhibitors (NRTIs), 4.4% to nonnucleos(t)ide reverse transcriptase inhibitors (NNRTIs), 2.3% to protease inhibitors (PIs), 0.2% to integrase strand transfer inhibitors (INSTIs) and 2.1% to at least two drug classes. TDR declined from 14.5% in 2006 to 7.3% in 2016 (P = 0.003): TDR to NRTIs from 9.9 to 2.9% (P = 0.003) and TDR to NNRTIs from 5.1 to 3.7% (P = 0.028); PI TDR remained stable. The proportion carrying subtype B virus declined from 76.5 to 50% (P < 0.001). The prevalence of TDR was higher in subtype B vs. non-B (12.6 vs. 4.9%, respectively; P < 0.001) and declined significantly in subtype B (from 17.1 to 8.8%; P = 0.04) but not in non-B subtypes (from 6.1 to 5.8%; P = 0.44). Adjusting for country of origin, predictors of TDR were subtype B [adjusted odds ratio (AOR) for subtype B vs. non-B 2.91; 95% confidence interval (CI) 1.93–4.39; P < 0.001], lower viral load (per log 10 higher: AOR 0.86; 95% CI 0.75–0.99; P = 0.03), site in northern Italy (AOR for southern Italy/island vs. northern Italy, 0.61; 95% CI 0.40–0.91; P = 0.01), and earlier calendar year (per 1 year more recent: AOR 0.95; 95% CI 0.91–0.99; P = 0.02). Conclusions: The prevalence of HIV-1 TDR has declined during the last 10 years in Italy

Genotypic resistance profiles associated with virological failure to darunavir-containing regimens: a cross-sectional analysis

INTRODUCTION: This study aimed at defining protease (PR) resistance mutations associated with darunavir (DRV) failure and PR resistance evolution at DRV failure in a large database of treatment-experienced human immunodeficiency virus (HIV) patients. RESULTS: Overall, 1,104 patients were included: 118 (10.7%) failed at a median observation time of 16\ua0months. The mean number of PR mutations at baseline was 2.7, but it was higher in patients who subsequently failed DRV. In addition, the number of PR mutations increased at failure. The increase in the mean number of mutations was completely related to mutations considered to be associated with DRV resistance following the indications of the main DRV clinical trials. DISCUSSION: The higher statistical difference at baseline between failing versus non-failing patients was observed for the V32I and I84V mutations. At DRV failure, the major increase was still observed for V32I; I54L, V11I, T74P and I50V also increased. Despite the increment in the mean number of mutations per patient between baseline and failure, in 21 patients (17.8%) at baseline and 36 (30.5%) at failure, no PR mutation was detected. CONCLUSION: The HIV-DB interpretation algorithm identified few patients with full DRV resistance at baseline and few patients developed full resistance at DRV failure, indicating that complete resistance to DRV is uncommon