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.

IntroductionSerious non‐AIDS events (SNAE) are frequent in HIV patients receiving cART. Current CD4 count was shown to be more strongly associated with infective compared to not‐infective SNAE and unable to predict cardiovascular events. We investigated the relationship between baseline and current CD4 count and the risk of both infective and non‐infective SNAE in HIV‐positive patients according to current ART use.MethodsWe included all HIV‐positive persons enrolled in the ICONA Foundation Study cohort who had at least one follow‐up visit. SNAE were grouped in infective (pneumonia, sepsis, endocarditis and meningitis) and non‐infective (malignancies, chronic kidney disease, cardiovascular events, hepatic events and pancreatitis) aetiology. Incidence of these event groups were calculated overall and according to baseline and current CD4 count (grouped as 0–200, 201–350, 351–500, 501–750, and >750 cells/mm3). Participants' follow‐up accrued from the date of enrolment (baseline) to a diagnosis of SNAE or their last visit. An event was defined the first time one of the considered SNAE occurred so that each person contributed a single event. A Poisson regression model for each of the two endpoints was used.ResultsA total of 10,822 patients were included (25.3% females, 38.2% heterosexuals) and 26.6% had hepatitis co‐infections. Median age was 36 (IQR 31–42) years. Overall, 423 not‐infective and 385 infective SNAE were included. The most frequent non‐infective SNAE were malignancies (n=202) and the most frequent infective SNAE were pneumonia (n=289). Crude rates of non‐infective SNAE were 0.78, 1.08 and 0.80/100 PYFU, and those of infective SNAE were 1.00, 0.51 and 0.66/100 PYFU in ART naive, currently off and currently on ART patients, respectively. Higher current CD4 count was associated with reduced risk of both infective and non‐infective SNAE in naives and in patients on ART (Table 1). The association was less strong in the group which suspended ART (for non‐infective SNAE the p value for interaction between current log‐CD4 and ART‐status, p=0.004). Conversely, we found no association between baseline CD4 count and risk of non‐infective SNAE in people treated with ART (p value for interaction = 0.0001). When CVD were considered separately, there was no association with CD4 count (not shown).ConclusionsOur findings show that, differently from ART naive, in ART‐treated patients, non‐infective SNAE are predicted by current but not by baseline CD4, suggesting that immune restoration is crucial to prevent these events.

IntroductionEmtricitabine/rilpivirine/tenofovir (EVP) is a fixed‐dose combination of antiretrovirals (ARV) approved by the European Medicines Agency in November 2011 and introduced in Italy in February 2013. It is a once‐a‐day single tablet and is licensed in Europe for use only in ARV‐naïve patients with a viral load (VL) ≤100,000 copies/mL.ObjectiveTo identify factors that may be associated with the use of EVP as first‐line regimen in HIV‐infected individuals starting cART from ARV‐naïve in Italy.MethodsClinical sites in ICONA Foundation Study in which ≥1 person had started EVP were selected for this analysis. From these we included all patients who started an EVP‐based cART regimen as well as those starting other cART regimens after the date of introduction of EVP at the site (after February 2013 in any case) and with a VL ≤100,000 copies/mL from ARV‐naïve. Characteristics at the time of starting cART were compared using chi‐square test and unadjusted and adjusted logistic regression analysis. Factors investigated included: gender, mode of HIV transmission, time from HIV diagnosis, CD4 count, nation of birth, AIDS, HCV‐status, age, CD8 count, VL, diabetes, smoking, total and HDL cholesterol, eGFR, blood glucose, level of education and employment and site location. Factors showing unadjusted associations with a p‐value of 10% or smaller, were retained in the multivariable model.ResultsWe identified 183 patients starting EVP and 173 starting the control regimen from 23 sites. The number of patients starting EVP included at each site ranged from 1 to 12 and the number of those starting the control regimen was similar. The most frequently used drugs in the concurrent group were: TDF (75%), FTC (74%), DRV (39%), ATV/r (26%), LPV/r (9%), EFV (13%) and RAL (14%). In univariable analysis, there were differences in median CD4 count (390 cells/mm3 in EVP versus 348 in controls, p=0.002), time from HIV diagnosis to starting cART (11 versus 3 months, p=0.001) and prevalence of students (6% versus 3%, p=0.07). No differences were observed for all other factors examined. The table shows estimates of the odds ratios (OR) for factors included in the multivariable model.ConclusionsCD4 count was higher in EVP‐treated patients compared to controls. Guidelines suggest avoiding initiation of EVP in presence of high VL, possibly explaining this residual difference in CD4. There was also a tendency to prescribe EVP to people with perceived lower adherence or hesitant to start or perhaps with a slow progressing disease.

IntroductionThe aim of this study was to analyze the likelihood and the predictors of discontinuation of first‐line regimen in the late HAART era.MethodologyAn observational multi‐center analysis of HIV‐positive patients enrolled in ICONA. Patients eligible were those starting a first‐line HAART after 1 January 2008. Discontinuation was defined as stop and/or switch of at least one drug of the regimen. All causes of discontinuation, as reported by the treating physician, were evaluated and cumulative risk of stopping was investigated according to age, gender, co‐morbidity, years since starting HAART, immuno‐virological status, third drug and backbone of the first regimen. Kaplan Meier (KM) analysis and Cox proportional hazards model were used for the outcome discontinuation of ≥1 drug regardless of the reason. For the KM estimates a competing risk approach was used to estimate the contribution of each of the reasons over time to the cumulative risk of stopping over time.ResultsData of 1759 patients who started first HAART and had at least one month of clinical follow‐up were analyzed. The overall discontinuation risk was 33% over a median follow‐up of 12 months. The likelihood of discontinuation by KM was 27% by one year (95% CI 25–29) and 41% by two years (95% CI 38–44). Main reason for stopping at least one drug in regimen was simplification (10%), followed by intolerance (7%), toxicity (5%), failure (2%) and other causes (8%). Estimates of the cumulative risk of discontinuation of ≥1 drug over time and according to reason are shown in Figure 1. In a multivariable Cox model independent predictors of discontinuation regardless of the reason were: longer time from HIV diagnosis to date of starting HAART (hazard ratio [HR] 0.96; 95% CI 0.93–1.00; p=0.039), regimens containing ZDV/3TC (HR 2.86; 95% CI 1.42–5.76; p=0.003 vs TDF/FTC) and an NNRTI‐based regimen (HR 2.47; 95% CI 0.91–6.72; p=0.07 vs regimens not NNRTI‐based).ConclusionsIn a previously reported analysis of the ICONA data [1], the overall risk of discontinuation of first‐line HAART was 36% with 21% due to intolerance/toxicity. In this updated analysis, the main reason for stopping is simplification (accounting for 32% of stops), reflecting the recent changes in recommendations aimed to minimize drug toxicity, enhancing adherence and quality of life.