Systemic inflammation-based scores and mortality for all causes in HIV-infected patients: a MASTER cohort study.

BACKGROUND: Two biomarkers, the neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR), have been shown to be indicative of systemic inflammation and predictive of mortality in general population. We aimed to assess the association of NLR and PLR, with risk of death in HIV-infected subjects when also taking account of HIV-related factors. METHODS: We conducted a multicenter Italian cohort study from 2000 to 2012 including HIV-infected subjects naïve at antiretroviral treatment. The associations of NLR and PLR with all-cause mortality were tested by univariate and multivariate analyses using both time independent and dependent Cox proportional hazard models. We also fitted models with a cubic-spline for PLR and NLR to evaluate the possible non-linear relationship between biomarkers values and risk of death. RESULTS: Eight-thousand and two hundred thirty patients (73.1% males) with a mean age of 38.4 years (SD 10.1) were enrolled. During a median follow-up of 3.9 years, 539 patients died. PLR < 100 and ≥ 200, as compared to PLR of 100-200, and NLR ≥ 2, as compared to < 2, were associated with risk of death at both univariate and multivariate analyses. Using multivariate models with restricted cubic-splines, we found a linear relationship of increasing risk of death with increasing values for NRL over 1.1, and an U-shape curve for PLR, with higher mortality risk for values higher or lower than 120. CONCLUSIONS: Our data suggest that NLR and PLR can reflect the severity of the underlying systemic disturbance of the inflammatory process and coagulation leading to augmented mortality in HIV positive subjects.

Systemic Inflammation-Based Biomarkers and Survival in HIV-Positive Subject With Solid Cancer in an Italian Multicenter Study.

BACKGROUND: Recently, some systemic inflammation-based biomarkers have been demonstrated useful for predicting risk of death in patients with solid cancer independently of tumor characteristics. This study aimed to investigate the prognostic role of systemic inflammation-based biomarkers in HIV-infected patients with solid tumors and to propose a risk score for mortality in these subjects. METHODS: Clinical and pathological data on solid AIDS-defining cancer (ADC) and non-AIDS-defining cancer (NADC), diagnosed between 1998 and 2012 in an Italian cohort, were analyzed. To evaluate the prognostic role of systemic inflammation- and nutrition-based markers, univariate and multivariable Cox regression models were applied. To compute the risk score equation, the patients were randomly assigned to a derivation and a validation sample. RESULTS: A total of 573 patients (76.3% males) with a mean age of 46.2 years (SD = 10.3) were enrolled. 178 patients died during a median of 3.2 years of follow-up. For solid NADCs, elevated Glasgow Prognostic Score, modified Glasgow Prognostic Score, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, and Prognostic Nutritional Index were independently associated with risk of death; for solid ADCs, none of these markers was associated with risk of death. For solid NADCs, we computed a mortality risk score on the basis of age at cancer diagnosis, intravenous drug use, and Prognostic Nutritional Index. The areas under the receiver operating characteristic curve were 0.67 (95% confidence interval: 0.58 to 0.75) in the derivation sample and 0.66 (95% confidence interval: 0.54 to 0.79) in the validation sample. CONCLUSIONS: Inflammatory biomarkers were associated with risk of death in HIV-infected patients with solid NADCs but not with ADCs.

The prognostic role of systemic inflammatory markers on HIV-infected patients with non-Hodgkin lymphoma, a multicenter cohort study.

BACKGROUND: The systemic inflammatory response has been postulated as having prognostic significance in a wide range of different cancer types. We aimed to assess the prognostic role of inflammatory markers on survival in HIV-infected patients with Non-Hodgkin Lymphoma (NHL), and to compute a prognostic score based on inflammatory biomarkers. METHODS: We evaluated data on HIV patients with NLH diagnosis between 1998 and 2012 in a HIV Italian Cohort. Using Cox proportional regression model, we assessed the prognostic role of Neutrophil-Lymphocyte Ratio (NLR), Platelet-Lymphocyte Ratio (PLR), Glasgow Prognostic Score (GPS), modified Glasgow Prognostic Score (mGPS), Prognostic Index (PI), and Prognostic Nutritional Index (PNI). We also computed a risk score equation, assigning patients to a derivation and a validation sample. The area under the curve (AUC) was use to evaluate the predictive ability of this score. RESULTS: 215 non-Hodgkin lymphoma cases (80.0% males) with a mean age of 43.2 years were included. Deaths were observed in 98 (45.6%) patients during a median follow up of 5 years. GPS, mGPS, PI and PNI were independently associated with risk of death. We also computed a mortality risk score which included PNI and occurrence of an AIDS event within six months from NHL diagnosis. The AUCs were 0.69 (95% CI 0.58 to 0.81) and 0.69 (95% CI 0.57 to 0.81) at 3 and 5 years of the follow-up, respectively. CONCLUSIONS: GPS, mGPS, PI and PNI are independent prognostic factors for survival of HIV patients with NHL.

Variability of raltegravir plasma levels in the clinical setting.

Therapeutic drug monitoring of raltegravir Ctrough levels was carried out in the setting of the Raltegravir Switch for Toxicity or Adverse events (RASTA) trial, a randomized pilot study exploring a 48-week safety and efficacy of treatment switch to raltegravir associated with tenofovir/emtricitabine or abacavir/lamivudine in patients with regimens with optimal virologic control. Blood sampling for measurement of raltegravir plasma levels was carried out at weeks 4, 12, 24, 36 and 48. Plasma samples were analysed by a recently developed and validated UPLC-MS method. A total of 164 samples from 39 patients were assayed. Analysis for intra- and inter-subject variability was restricted to those patients with 4 or more determinations, including 30 patients and 142 determinations. The intra- and inter-subject variability measures were 85.9 and 124.6%, respectively, with an intra-/inter-subject variability ratio of 69%. We also analysed data from a subset of patients with well-documented adherence to protocol, defined as protocol compliant population, including 21 patients and 93 determinations. In this subpopulation, we estimated intra- and inter-subject variability of 79.87% and 110%, respectively, with an intra-/inter-subject variability ratio of 72.6%. This study confirms the notion that raltegravir is a highly variable drug according to the European Medicines Agency criteria. While this condition does not favour the adoption of therapeutic drug monitoring in the clinical practice, the latter is deemed useful in patients with drug plasma concentrations below or near the threshold level of efficacy (since intracellular raltegravir levels might be as low as 5% of the corresponding plasma levels), or to identify drug-drug interactions of potential clinical relevance.