Suchergebnisse

IntroductionIn clinical trials, toxicity leading to discontinuation of tenofovir (TDF) is a rare occurrence (3% by two years)[1, 2]; however, in clinical practice it seems to be higher. Previous studies suggested that TDF toxicity is higher when it is co‐administered with ritonavir‐boosted protease inhibitors (PI/r)[3, 4]. The aim of this study is to assess the rate of TDF discontinuations in clinical practice and to explore associated factors.MethodsAll previously antiretroviral‐naïve patients initiating a TDF‐containing regimen were selected from the ICONA cohort, unless they were positive for hepatitis B. The primary outcome was TDF discontinuation (>30 days) regardless of the reason, the secondary was TDF discontinuation due to toxicity. All analyses were repeated for the isolated stop of TDF (no stop of associated drugs). The main reason for discontinuation as reported by the treating physicians was used to classify stops. Kaplan–Meier (KM) analysis and Cox proportional hazards model were used.ResultsA total of 3,303 naïve patients were enrolled: 674 (20.4%) were female, the median age was 38 years (32–45), 55% were on PI/r‐based regimen and 45% on NNRTI; 80% of calculated estimated glomerular filtration rates (eGFR) were >90 ml/min. The probability of discontinuation of TDF regardless of the reason was 10% (95% CI 8–11) at two years, 20% by eight years. The causes of discontinuation were: toxicity (33%), failure (10%), non‐adherence (21%), simplification (16%) and other/unknown causes (20%). The five‐year KM estimates in the PI/r vs. not PI/r groups were 23% vs. 10%, respectively (log‐rank p=0.0001), for the outcome of stopping regardless of the reason, and 8% vs. 4% (p=0.18) for discontinuation due to toxicity. In a multivariable Cox model, PI/r use and lower body weight were associated with increased risk of discontinuing TDF regardless of the reason; lower eGFR at baseline was associated with TDF discontinuation for toxicity and PI/r use was associated with isolated stop of TDF (Figure). No differences in rates of TDF discontinuations between PIs were found.ConclusionIn our cohort, the observed frequency of TDF discontinuations was low although higher than estimated in clinical trials (10% by two years). Co‐administration of TDF with PI/r was associated with an increased rate of TDF discontinuations. This finding should guide further investigations of the mechanism that may have led to discontinuation of TDF in patients using PI/r.

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.

IntroductionWe aimed at evaluating the efficacy and durability of a lopinavir/ritonavir‐based dual regimen (LPV/r‐DR) in virologically controlled HIV‐infected individuals in current clinical practice.MethodsPatients who have initiated for the first time a LPV/r‐DR with HIV‐RNA<50 copies/mL were included in this observational study. The main endpoints were: time to virological rebound [VR=time of first of two consecutive viral loads (VL)>50 copies/mL] and time to experience either a single VL>200 copies/mL or discontinuation/intensification (= treatment failure, TF). Individuals' follow‐up accrued from the date of starting the LPV/r‐DR to event or last available VL. Kaplan‐Meier curves and Cox regression analysis were used. Covariates included in the multivariable analysis were gender, age, route of transmission, hepatitis co‐infection, calendar year of starting the DR, nadir CD4+ count, VL at initiation of first cART, previous failures to protease inhibitors (PIs), time with undetectable VL before starting the DR and the type of DR [nucleoside reverse transcriptase (NRTI), non‐NRTI (NNRTI), raltegravir or maraviroc, with NRTI as reference group]. Results are presented as median (Q1, Q3) or frequency (%) as appropriate.Results108 individuals followed for 18 (7, 30) months were included; baseline (BL) characteristics are detailed in Table 1.LPV/r was associated with a NRTI in 51, with a NNRTI in 10, with raltegravir in 29, and with maraviroc in 18 individuals. By 36 months from switching to the LPV/r‐DR, the proportion of individuals with VR and TF was 10% (95% CI 3–17%) and 36% (95% CI 22–50%), respectively. We did not find any factor independently associated with the risk of VR. Older age (ARH=0.49 (95% CI 0.30–0.78) per 10 years older; p=0.003) was found to be protective from TF. Mean (SE) CD4+ cells/µL increase from BL to month 36 resulted significant: 195 (40.1) cells/µL (p=0.0028). We did not observe significant changes in AST, ALT, eGFR (MDRD formula), triglycerides and both total and HDL‐cholesterol.ConclusionsA LPV/r‐DR can be considered a valuable option in patients with HIV‐RNA<50 copies/mL and ongoing toxicity from the third drug of the regimen, although up to 17% of patients showed viral rebound by 3 years. Older patients are at lower risk of failure with this strategy, but larger sample size is needed to identify who might benefit from this strategy instead of others.