Suchergebnisse

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.

IntroductionSince antiretroviral therapy must be taken lifelong, persistence and safety have become the goals to achieve. Protease inhibitors, in particular atazanavir (ATV) with or without ritonavir (r), represent a highly prescribed class in real life long‐term treatment.MethodsWe conducted a retrospective cohort study in HIV‐1‐positive patients who were followed at the Infectious Diseases Unit, DIBIC Luigi Sacco, University of Milan. Data regarding viral load, CD4 lymphocytes and the mean blood chemistry parameters were collected at baseline, first, third, sixth months from the beginning of therapy and then every six months. Factors related to persistence of therapy with ATV and time‐dependent probability to reach a CD4 cells count >500 cells/µL were evaluated with Kaplan‐Meier curve and Cox model.ResultsA total of 1030 patients were evaluated: 183 received therapy with ATV/r as naïve, 653 switched to ATV/r as a second or following line and 194 switched to unboosted ATV from previous ATV‐free regimens. A total of 138 patients shifted to unboosted ATV from a previous ATV/r regimen (17 from naïve ATV/r and 121 from experienced ATV/r). The median duration of therapy was 38 months (95% CI 29–73) in ATV/r naïve patients, 36 months (95% CI 23–53) in unboosted ATV group and 35 months (95% CI 31–43) in patients switched to ATV/r. We observed no significant difference in the persistence of the three regimens (p=0.149). Female (HR=1.317; 95% CI 1.073–1.616 p=0.008) and patients with CD4<200 cells/µL at baseline (HR=1.433 95% CI 1.086–1.892 p=0.011) were at increased risk of regimen interruption, whereas starting therapy with a backbone containing abacavir (HR=0.725; 95% CI 0.533–0.987 p=0.041) resulted protective. In multivariate analysis no significant difference between the three regimens was observed regarding reaching a count of CD4 cells >500 cells/µL. Factors associated to a poor CD4 gain were each extra Log of viral load at baseline (HR=0.915; 95% CI 0.852–0.982 p=0.014) and CD4<200 cells/µL at ATV start (HR=0.197; 95%CI 0.138–0.281 p<0.0001); conversely, females (HR=1.262; 95%CI 1.032–1.543 p=0.023) had a higher probability of CD4 recovery.ConclusionsAntiretroviral regimens containing atazanavir with or without ritonavir were durable and well tolerated, an elevated viral load and CD4 <200 cells/µL at baseline resulted related to regimen discontinuation and reduced CD4 recovery.

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.

IntroductionThe optimal timing and modality of therapeutic intervention during early phases of HIV infection is still debated; in our prospective observational study we evaluated immunological and virological outcome in HIV+ patients treated during acute or recent HIV infection.Materials and MethodsA total of 25 naïve patients with acute (detectable HIV‐RNA, immature Western Blot) or recent (documented infection within six months) HIV infection were recruited at the Infectious Diseases Units of the University of Milan and Turin from 2009 to 2014. Patients received treatment with two NRTIs+one NNRTI/bPI, with or without an induction phase with an additional fourth drug (raltegravir or maraviroc) until HIV‐RNA undetectability maintained for six months. Blood samples for HIV‐RNA, lymphocyte subsets and tropism assessment were obtained at the beginning of the treatment (BL). Patients underwent subsequent six‐monthly follow up for clinical outcome, CD4 cell count and HIV‐RNA up to 18 months.ResultsMedian increase in CD4 cells from 0 to 12 months was greater in patients treated during acute (n=18) versus recent (n=7) infection [284/µL, IQR (227–456) versus 176/µL, IQR (70–235); Mann‐Whitney test, p=0.046]. This higher value was maintained through 18 months, although failing to reach statistical significance. Patients with acute or recent infection did not significantly differ in virological success (83.3% versus 85.7% at 12 months). We considered CD4 cells gains at six months (multivariate analysis, ANCOVA; Figure 1) and detected an inverse correlation with CD4 levels at BL (r=−0.517; p=0.008) and a direct correlation with the status of acute infection (r=0.234, p NS). This last correlation reached statistical significance at 12 months (r=0.418, p=0.035), whereas the inverse correlation with CD4 levels at BL was still present without a statistical significance (r=−0.350; p=0.072). Patients treated with three or four drugs did not show any significant difference in immunological nor virological response (Mann‐Whitney and χ2 test). Modification or interruption of therapy for tolerability took place in 4 out of 25 patients, all while receiving four drugs; two patients underwent STI between 12 and 18 months following virological success.ConclusionsTreatment of primary infection appeared to be effective in preserving the pool of CD4 cells in acute more than recent infection. There was no evidence of a different outcome through the addition of a fourth drug to the standard treatment.