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.

IntroductionLow level HIV‐1 CSF replication (CsfLLV) is often found even in patients with controlled plasma viraemia. The clinical consequences of such finding are uncertain; however, both symptomatic neurological disturbances and neurocognitive disorders may arise in the context of CSF‐escape. Two reports suggested that low level replication in the CSF may be associated with increased CSF neopterine although the impact on other markers of neuroinflammation/damage is currently unknown.Materials and MethodsPatients with neurocognitive disorders, new neurological symptoms or followed in longitudinal studies were included provided that they were on HAART, with last available viral load below 20 copies/mL and without central nervous system (CNS)‐involving infections/neoplasms. After brain Magnetic Resonance (MR) CSF HIV RNA (CAP/CTM HIV‐1 v2.0) and biomarkers [total tau (t‐tau), phosphorylated tau (p‐tau), 1–42 Beta amyloid (Beta42), neopterine and S100beta] were measured through validated methods. Data are presented as medians (IQR); non‐parametric tests are used for all analysis.Results70 patients [66.7% male, median age 47.8 years (40–56), median BMI 22.2 kg/m2 (20–24)] were enrolled. Current and nadir CD4+ cell count were 379 (219–656) and 116 cell/mm3 (46–225); HIV RNA was undetectable since 19.7 months (9–53). CSF HIV RNA was undetectable in 24 (34.3%), below 20 copies/mL in 26 (37.1%), above 20 copies/mL in 25 patients [35.7%, median 69 copies/mL (41–134]). Median (IQR) CSF biomarkers values were as follows: t‐tau 109 pg/mL (<75–161), p‐tau 31.6 pg/mL (23.4–35.4), Beta42 818 pg/mL (623–973), neopterine 0.58 ng/mL (0.45–0.87) and S100beta 149 pg/mL (110–186). Patients with CsfLLV did not show significant differences as for demographic, therapeutic, virological, radiological variables. t‐tau (134 vs 92.6, p=0.05) and Beta42 (953 vs 675, p=0.007) were higher in patients with CsfLLV. Neopterine levels were directly associated with p‐tau (rho=0.42, p=0.01), with CSF HIV RNA (rho=0.24, p=0.06). and inversely with current CD4 cell count (rho=−0.29, p=03).ConclusionsIn patients with controlled HIV viraemia (below 20 copies/mL), CSF total tau, Beta42 and neopterine were higher in patients with detectable HIV RNA. Prospective and adequately powered studies are warranted for evaluating the clinical significance of compartmental viral replication and immune activation.

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 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.

Action on social determinants is a main component of the World Health Organization End Tuberculosis (TB) Strategy. The aim of the study was to collect information on socioeconomic characteristics and biomedical risk factors in migrant TB patients in Italy and compare it with data collected among Italian TB patients. A cross-sectional study was conducted among TB patients aged ≥18 years over a 12-months enrolment period in 12 major Italian hospitals. Information on education, employment, housing and income was collected, and European Union Statistics on Income and Living Conditions index was used to assess material deprivation. Among migrants, we also analyzed factors associated with severe material deprivation. Migrants were compared with younger (18-64 years) and older (65+ years) Italians patients. Out of 755 patients enrolled (with a median age of 42 years, interquartile range: 31-53), 65% were migrants. Pulmonary, microbiologically confirmed, and new cases were 80%, 73%, and 87% respectively. Prevalence of co-morbidities (i.e. diabetes, chronic kidney disease, neoplastic diseases and use of immunosuppressive drugs) was lower among migrants compared to Italian TB patients, while indicators of socioeconomic status, income and housing conditions were worst in migrants. Forty-six percent of migrants were severely deprived vs. 9% of Italians (p<0.0001, 11.3% and 5.5% among younger and older Italians, respectively). Among migrants, being male, older, irregular, unemployed, with a shorter time spent in Italy, a lower education level, and without a co-morbidity diagnosis were factors associated with severe material deprivation at multi-variable logistic regression. Moreover, socioeconomic indicators for Italian patients did not differ from those reported for the general Italian population, while migrant TB patients seem to have a higher prevalence of severe material deprivation than other migrants residing in Italy. Intervention to address the needs of this population are urgent.