Suchergebnisse

IntroductionIn a recent clinical trial (ACTG 5257), no difference in viral failure (VF) of a first‐line cART containing atazanavir/r (ATV/r) or darunavir/r (DRV/r) was found [1]. For the endpoint of discontinuation due to intolerance, the regimen with DRV/r was superior to that of ATV/r (49% of the stops of ATV/r were attributed to jaundice or hyperbilirubinemia). These and other intolerances to ATV/r remain a concern for clinicians.MethodsParticipants in the ICONA Foundation Study who started cART with 2NRTI+ ATV/r or DRV/r while ART‐naïve were included. Several endpoints were evaluated: confirmed VF>200 copies/mL after six months of therapy, discontinuation of DRV/r or ATV/r for any reasons or because of intolerance/toxicity (as reported by the treating physician) and the combined endpoint of VF or stop. Survival analysis with Kaplan–Meier curves and Cox regression model stratified by clinical site was used. Patients' follow‐up accrued from cART initiation to the date of the event or to the date of last available visit/viral load.Results894 patients starting 2NRTI+ATV/r and 686 2NRTI+DRV/r when ART‐naïve on average in 2011 (IQR: 2010–2012) were studied. Most common NRTIs used were FTC/TDF (84%) and ABC/3TC (12%). Median age was 40 years, 22% females, 44% heterosexuals. Patients starting ATV/r were more likely to be hepatitis B/C infected (2% and 14% vs 1% and 9%, p=0.001), they started one year earlier (2011 vs 2012, p=0.001), were more likely to be enrolled in sites located in the north of Italy (63% vs 54%, p=0.04), started cART less promptly after HIV diagnosis (5 vs 2 months, p=0.02) and less likely to have started TDF/FTC (83% vs 85%, p=0.02). By two years of cART, 9.8% (95% CI 7.6–12.0) of those starting ATV/r experienced discontinuation due to intolerance/toxicity vs 6.5% in DRV/r group (95% CI 4.2–8.8, p=0.04). After controlling for several potential confounders (age, gender, nation of birth, mode of HIV transmission, hepatitis co‐infection status, AIDS diagnosis, nucleoside pair started, baseline CD4 count and viral load and year of starting cART) the relative hazard (RH) for ATV/r vs DRV/r was 2.01 (95% CI 1.23, 3.28, p=0.005). There were no statistical differences detected for any of the other outcomes.ConclusionsAlthough unmeasured confounding cannot be ruled out, our results seem to be consistent with those of the ACTG 5257. When all cause discontinuations were considered, or the composite endpoint of treatment failure, there was no difference between ATV/r‐ and DRV/r‐based regimens.

IntroductionWe report interim 24‐weeks efficacy data of ATLAS‐M trial, a phase IV, multicentre, open‐label, randomized study designed to show 48‐weeks, non‐inferior efficacy (margin of −12%) of treatment simplification to atazanavir/ritonavir (ATV/r)+lamivudine (3TC) versus maintaining 3‐drugs ATV/r‐based cART.MethodsSubjects on ATV/r+2 NRTIs, without previous treatment failure (TF), with HIV‐RNA <50copies/mL for >3 months and CD4>200 cells/mm3 for >6 months were eligible. At baseline, patients were randomized to switch to ATV/r+3TC (arm one) or to maintain the original 3‐drug regimen (arm two). Primary endpoint: proportion of patients free of TF at week 48. TF was defined as treatment modification for any reason, including virological failure (VF=two consecutive HIV‐RNA>50 copies/mL or a single value >1000 copies/mL). Enrollment of 266 patients was planned.ResultsA total of 266 patients (78% males, median age 44 years, median CD4 603 cells/µL, 79% treated with a tenofovir‐containing backbone) were enrolled. At the time of analysis, 24 weeks data were available for 84 and 87 patients in arm one and two, respectively. At baseline, subjects in the two arms did not differ for the main characteristics. At 24 weeks, at the intention to treat analysis the proportion of patients free of TF was 91.7% (95% CI 85.8–97.6) and 85.1% (95% CI 77.6–92.6) in arm one and two, respectively (difference +6.6%, 95% CI −2.9/+16.1). VF was observed in two patients randomized to arm one (one at baseline, before treatment simplification) and one to arm two without resistance mutations. Clinical and laboratory adverse events occurred at similar rates in the two arms. At week 24, patients in arm one showed a greater increase in CD4 (mean change +90 vs +10 cells/µL, p=0.007). A greater increase in total cholesterol (+18 vs −2 mg/dL, p<0.001), HDL (+4 vs +0 mg/dL, p=0.001) and LDL (+12 vs +0 mg/dL, p=0.001) was also observed in arm one without differences in other lipid parameters. Renal function showed a significant improvement in arm one (mean change in eGFR +5 vs −2 mL/min/1.73m2 in arm two, p=0.001). No significant differences in bilirubin levels or other laboratory parameters were observed between the two arms.ConclusionsThis interim analysis suggests a 24‐weeks non‐inferior efficacy of treatment simplification to ATV/rit+3TC as compared to continuation of ATV/rit +2 NRTI in virologically suppressed patients. Follow‐up until 48‐weeks is scheduled to confirm these data.