Does enfuvirtide increase the risk of bacterial pneumonia in patients receiving combination antiretroviral therapy?

BACKGROUND: Pooled analysis of the TORO comparative clinical trial data sets showed a significantly higher incidence rate (IR) of bacterial pneumonia (BP) among patients treated with enfuvirtide-containing combination antiretroviral therapy (ENF-cART) than in those treated with other cART regimens. OBJECTIVES: To examine the possible impact of ENF-cART on the risk of BP. METHODS: From the French Hospital Database on HIV, we selected two groups of patients among cART-treated patients who were prescribed a new cART regimen during the period 2001-2006, when their CD4 counts were <350 cells/mm(3). The ENF-cART and cART groups consisted of 1220 and 9374 patients, respectively. Poisson regression models were used to quantify the relationship between ENF-cART therapy and the risk of BP. RESULTS: At baseline the median CD4 counts were 100 and 211 cells/mm(3) and the median plasma viral load (pVL) values were 60 276 and 2702 copies/mL in the ENF-cART and cART groups, respectively. The respective BP IRs were 0.65 [95% confidence interval (CI) 0.25-1.06] and 0.31 (95% CI 0.25-0.38) cases per 100 person-years. After adjustment for age, the HIV transmission group, the time period, co-trimoxazole prophylaxis, and stratified CD4 cell counts and pVL values, we found that the BP risk ratio was not increased by enfuvirtide treatment (relative rate 1.39; 95% CI 0.46-4.13). In contrast, lower CD4 cell counts and higher pVL values were significantly associated with a higher risk of BP. CONCLUSIONS: ENF-cART is not associated with a significantly higher risk of BP than other cART regimens, although the value of the adjusted risk and the upper limit of the CI do not allow us to exclude a small increased risk.

Clinical interest of bone texture analysis in osteoporosis: a case control multicenter study.

UNLABELLED: We demonstrate the clinical interest of bone texture analysis with a new high resolution X-ray device. We have found that the combination of BMD and texture parameter values provided a better assessment of the fracture risk than that obtainable solely by BMD measurement. INTRODUCTION: Osteoporosis is characterized by BMD and trabecular bone microarchitecture. We have developed a new high-resolution X-ray device with direct digitization. The aim of this study was to demonstrate in a multicenter case control study the clinical interest of bone texture analysis with this new device. METHODS: In this cross-sectional multicenter case-control population study in post-menopausal women, 159 osteoporotic fractures were compared with 219 control cases. Images were obtained on calcaneus with a direct digital X-ray device (BMA, D3A Medical Systems). Co-occurrence, run-length matrices and the fractal parameter Hmean were evaluated. BMD was measured at the lumbar spine (LS), femoral neck (FN) and total hip (TH) by DXA. RESULTS: The three texture parameters were significantly lower in osteoporotic fracture cases than in control cases. These differences persisted after adjustment for TH BMD. Receiver operating characteristic curves were used to compare the discriminant capacity of texture parameters and BMD measurements for fracture. The highest areas under curve (AUC) were 0.721 for TH BMD and 0.706 for Hmean (AUC THBMD vs. AUC Hmean, p = NS). We determined the threshold between high and low Hmean parameter values and then the odds ratios (OR) of fracture for low Hmean, for BMD < or =2.5 SD in the T-score and for combinations of both parameters. The OR of fracture for low H was 2.72 (95% CI, 1.36-5.4). For a FN BMD < or = -2.5 SD, the OR of 4.78 (2.19-10.43) shifted to 14.06 (4.41-44.85) adding H. CONCLUSIONS: These data confirmed the clinical interest of the combination of BMD and texture parameters to improve the assessment of the risk of fracture other that obtainable by the sole BMD measurement.

n-3 polyunsaturated fatty acid supplementation reverses stress-induced modifications on brain monoamine levels in mice.

The aim of this study was to examine the effects of supplementation with n-3 polyunsaturated fatty acids (PUFAs) on stress responses in mice subjected to an unpredictable chronic mild stress (UCMS) procedure. Stress-induced modifications in coat and aggressiveness were evaluated, and phospholipid PUFA profiles and monoamine levels were analyzed in the frontal cortex, hippocampus, and striatum. The results showed that repeated exposure to mild stressors induced degradation in the physical state of the coat, lowered body weight gain, and increased aggressiveness, without any effect of n-3 PUFA supplementation. The UCMS induced a significant decrease in the levels of norepinephrine in the frontal cortex and striatum, and a nonsignificant decrease in the hippocampus. The tissue levels of serotonin (5-HT) were 40% to 65% decreased in the three brain regions studied. Interestingly, the n-3 PUFA supplementation reversed this stress-induced reduction in 5-HT levels. These findings showed that supplementation in n-3 long-chain PUFAs might reverse certain effects of UCMS in cerebral structures involved in stress-related behaviors.

Markov modelling of changes in HIV-specific cytotoxic T-lymphocyte responses with time in untreated HIV-1 infected patients.

HIV-specific cytotoxic CD8(+) T-lymphocytes (CTL) appear to be the cornerstone of the immune response to HIV infection. Recent studies show that CTL activity reflects patients' anti-HIV immune status and slows disease progression. However, the dynamics of the diversity of this response also appears as a key parameter for immune control but the dynamics of this diversity is largely undocumented. We modelled changes in CTL responses against the seven principal HIV proteins over time. We also studied the influence of plasma viral load on temporal changes in HIV protein recognition by memory CTL. The generic model we developed is based on a continuous time homogeneous Markov process with reversible states. Those states are defined by the number of proteins recognized by memory CTL in a given patient at a given time. This approach was developed within a Bayesian framework. Full Bayesian inference is implemented using Markov chain Monte Carlo simulations (MCMC). The Gibbs sampling algorithm was used to estimate the marginal posterior distributions of the transition intensities between stages of CTL responses. We applied our model to data of 152 HIV-infected patients included in the IMMUNOCO cohort. The model suggested that the diversity of HIV protein recognition by memory CTL in treatment-naive patients decreases as the disease progresses. Namely, the loss of T cytotoxic responses is globally faster than their acquisition. Indeed, these patients' T cytotoxic responses were characterized by marked individual turnover and a gradual loss of multiple protein recognition over time, this loss accelerating as viral load increased.