Body fat distribution in HIV-infected patients treated for 96 weeks with darunavir/ritonavir monotherapy versus darunavir/ritonavir plus nucleoside reverse transcriptase inhibitors: The MONOI-ANRS136 Substudy
Valantin M.A.,University Pierre and Marie Curie |
Kolta S.,University of Paris Descartes |
Flandre P.,University Pierre and Marie Curie |
Algarte Genin M.,University Pierre and Marie Curie |
And 7 more authors.
HIV Medicine | Year: 2012
Objectives: The aim of the study was to evaluate fat tissue distribution in HIV-infected patients with suppressed viraemia treated with darunavir/ritonavir (darunavir/r) monotherapy versus darunavir/r triple therapy. Methods: This study was a substudy of the randomized, multicentre, open-label MONOI-ANRS 136 trial. Body fat distribution and metabolic parameters were measured at baseline, week 48 and week 96. Results: In total, 156 patients of the 225 initially enrolled in the MONOI trial participated in this study, 75 in the darunavir/r monotherapy arm and 81 in the darunavir/r triple-therapy arm. The median limb fat increase from baseline was +0.34kg [interquartile range (IQR) -0.040 to +1.140kg; P<0.001] at week 48 and +0.33kg (IQR -0.14 to +1.26kg; P=0.001) at week 96 in the monotherapy arm, while there was no change (-0.02kg; IQR -0.53 to +0.52kg) at week 48 and then an increase of +0.23kg (IQR -0.45 to +0.87kg; P=0.046) at week 96 in the triple-therapy arm. The two arms differed significantly at week 48 (P=0.001) but not at week 96. The median increase in trunk fat was +0.73kg (IQR -0.24 to +1.60kg; P<0.001) and 0.60kg (IQR -0.41 to +1.49kg; P=0.03) at week 48 and +1.16kg (IQR -0.17 to +2.75kg; P<0.001) and +0.90kg (IQR -0.51 to +2.34kg; P=0.001) at week 96 in the monotherapy and triple-therapy arms, respectively, with no difference between arms. At week 96, the only biological change was a glucose level elevation in the monotherapy arm (median +4.0mg/dL; IQR -4.0 to +7.0mg/dL) compared with the triple-therapy arm (P=0.012). Conclusions: Overall, body fat tissue increased in patients on darunavir/r monotherapy and triple therapy, with no difference between the arms over 96 weeks. The only difference found was a delayed increase in limb fat tissue in the triple-therapy arm compared with the monotherapy arm in the first year.© 2012 British HIV Association.
Payet S.,Clermont Ferrand Teaching Hospital |
Soubrier M.,Clermont Ferrand Teaching Hospital |
Perrodeau E.,Strasbourg Teaching Hospital |
Bardin T.,Bicetre Teaching Hospital |
And 9 more authors.
Arthritis Care and Research | Year: 2014
Objective. The aim of this study was to compare the efficacy and safety of rituximab (RTX) as a function of patient age. Methods. We included all rheumatoid arthritis patients in the AutoImmunity and Rituximab registry with a 2-year followup. Results. Of the 1,709 patients, 191 were age ≥75 years, 417 were ages 65-74 years, 907 were ages 50-64 years, and 194 were age <50 years. At baseline, the elderly and very elderly patients presented with longer disease duration, a higher incidence of erythrocyte sedimentation rate and C-reactive protein level, a lower incidence of previous tumor necrosis factor α (TNFα) therapy, and a smaller number of previously used TNFα agents. Disease activity, rheumatoid factor (RF), or anti-cyclic citrullinated peptide (anti-CCP) antibodies and corticosteroid therapy were not statistically different among the groups. At 24 months, no significant difference was shown among the groups for RTX discontinuation rates (36.1% if age <50 years, 32.6% if ages 50-64 years, 34.5% if ages 65-74 years, and 32.5% if age >75 years). The reasons for discontinuation (inefficacy, adverse events) were the same in all 4 groups. Infections were more common in the elderly. Patients ages 65-75 years were more likely to be good responders than nonresponders at 1 year of followup than patients age ≥75 years (odds ratio 3.81, 95% confidence interval 1.14-12.79) after adjustment on disease duration, RF/anti-CCP positivity, corticosteroids, anti-TNF use, and baseline Disease Activity Score in 28 joints (DAS28). After the sixth month, the decrease in DAS28 score was less marked in the population age >75 years than in the group age <50 years. Conclusion. The efficacy and safety of RTX is affected by age. Copyright © 2014 by the American College of Rheumatology.
Leibowitch J.,Hopital Raymond Poincare |
Mathez D.,Hopital Raymond Poincare |
De Truchis P.,Hopital Raymond Poincare |
Ledu D.,Hopital Raymond Poincare |
And 5 more authors.
FASEB Journal | Year: 2015
Short, intraweekly cycles of anti-HIV combinations have provided intermittent, effective therapy (on 48 patients) (1). The concept is now extended to 94 patients on treatment, 4 days per week or less, over a median of 2.7 discontinuous treatment years per patient. On suppressive combinations, 94 patients volunteered to treatment, 5 and 4 days per week, or reduced stepwise to 4, 3, 2, and 1 days per week in 94, 84, 66, and 12 patients, respectively, on various triple, standard, antiviral combinations, or nonregistered, quadruple, antiviral combinations. Ninety-four patients on treatment 4 days per week aggregated 165 intermittent treatment years; no viral breakthrough was observed over 87 average treatment weeks per patient, 63 of 94 having passed 2.5 intermittent treatment years on any of the antiviral combinations prescribed. On the hyperintermittent treatment of 3, 2, and 1 days per week, HIV RNA surged >50 copies, 4 weeks apart, in 18 instances (6.8 viral escapes/100 hyperdiscontinuous maintenance years). Viralescapes could have been a result of erratic adherence (EA) to regimen or follow-up (3 patients)-drug taken at half of the daily recommended dosage (8 patients) and/or overlooked archival-resistant HIVs from antecedent treatment failures (6 patients). Aside from the above circumstances, HIV unexpectedly rebounded in 3 patients on 2 days per week treatment and 1 patient on 1 day per week treatment, posting 2.2 intrinsic viral escapes/100 highly discontinuous treatment years. All 18 escapes were eventually reversed by 7 days per week salvage combinations, and 11 of 18 patients have been back for a second course of intermittent therapy, 4 days per week or less. Both cell-activation markers on the surface of T lymphocytes and cell-bound HIV DNA levels remained stable or declined. CD4/CD8 ratios rose to ≥1 in 35%ofpatients,whereasCD4countswent ≥500/μlin 75%. These values were previously 7 and 40%, respectively, on 7 days per week therapy. In our aging, long, HIV-enduring, multitreated patient cohort, treatment 4 days per week and less over 421 intermittent treatment years reduced prescription medicines by 60%-equivalent to 3 drug-free/3 virus-free remission year per patient-actually sparing ∈3 million on just 94 patients at the cost of 2.2 intrinsic viral failure/100 hyperintermittent treatment years. At no risk of viral escape, maintenance therapy, 4 days per week, would quasiuniversally offer 40% cuts off of current overprescriptions.-Leibowitch, J., Mathez, D., de Truchis, P., Ledu, D., Melchior, J. C., Carcelain, G., Izopet, J., Perronne, C., David, J. R. Four days a week or less on appropriate anti-HIV drug combinations provided long-term optimal maintenance in 94 patients: the ICCARRE project. 0892-6638/15/0029-2223 © FASEB.
White P.M.,University of Edinburgh |
Lewis S.C.,University of Edinburgh |
Gholkar A.,Newcastle General Hospital |
Sellar R.J.,University of Edinburgh |
And 4 more authors.
The Lancet | Year: 2011
Background: Coated coils for endovascular treatment of cerebral aneurysm were developed to reduce recurrence and retreatment rates, and have been in clinical use for 8-9 years without robust evidence to determine their efficacy. We assessed the efficacy and safety of hydrogel-coated coils. Methods: This randomised trial was undertaken in 24 centres in seven countries. Patients aged 18-75 years with a previously untreated ruptured or unruptured cerebral aneurysm of 2-25 mm in maximum diameter were randomly allocated (1:1) to aneurysm coiling with either hydrogel-coated coils or standard bare platinum coils (control). Randomisation was done with a computer-generated sequence, stratified by aneurysm size, shape, and dome-to-neck ratio; intention to use assist device; and by region. Participants and those assessing outcomes were masked to allocation. Analysis was by modified intention to treat (excluding missing data). Primary outcome was a composite of angiographic and clinical outcomes at 18-month follow-up. We also did prespecified subgroup analyses of characteristics likely to be relevant to angiographic outcome. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN30531382. Findings: 249 patients were allocated to the hydrogel coil group and 250 to the control group. In 44 of 467 patients for whom an 18-month composite primary outcome was unavailable, 6-month angiographic results were used. 70 (28) patients in the hydrogel group and 90 (36) control patients had an adverse composite primary outcome, giving an absolute reduction in the proportion of adverse composite primary outcomes with hydrogel of 7·0 (95 CI -1·6 to 15·5), odds ratio (OR) 0·73 (0·49-1·1, p=0·13). In a prespecified subgroup analysis in recently ruptured aneurysms, there were more adverse composite primary outcomes in the control group than in the hydrogel group - OR 2·08 (1·24-3·46, p=0·014). There were 8·6 fewer major angiographic recurrences in patients allocated to hydrogel coils - OR 0·7 (0·4-1·0, p=0·049). There were five cases of unexplained hydrocephalus in not-recently-ruptured aneurysms in the hydrogel coil group and one case in the control group. Interpretation: Whether use of hydrogel coils reduces late aneurysm rupture or improves long-term clinical outcome is not clear, but our results indicate that their use lowers major recurrence. Funding: MicroVention Inc. © 2011 Elsevier Ltd.
Bretagnol F.,Beaujon Hospital |
Panis Y.,Beaujon Hospital |
Rullier E.,St. Andre Hospital |
Rouanet P.,Val dAurelle Institute |
And 6 more authors.
Annals of Surgery | Year: 2010
Objective: To assess with a single-blinded, multicenter, randomized trial, the postoperative results in patients undergoing sphincter-saving rectal resection for cancer without preoperative mechanical bowel preparation (MBP). Background: The collective evidence from literature strongly suggests that MBP, before elective colonic surgery, is of no benefit in terms of postoperative morbidity. Very few data and no randomized study are available for rectal surgery and preliminary results conclude toward the safety of rectal resection without MBP. Methods: From October 2007 to January 2009, patients scheduled for elective rectal cancer sphincter-saving resection were randomized to receive preoperative MBP (ie, retrograde enema and oral laxatives) or not. Primary endpoint was the overall 30-day morbidity rate. Secondary endpoints included mortality rate, anastomotic leakage rate, major morbidity rate (Dindo III or more), degree of discomfort for the patient, and hospital stay. Results: A total of 178 patients (103 men), including 89 in both groups (no-MBP and MBP groups), were included in the study. The overall and infectious morbidity rates were significantly higher in no-MBP versus MBP group, 44% versus 27%, P = 0.018, and 34% versus 16%, P = 0.005, respectively. Regarding both anastomotic leakage and major morbidity rates, there was no significant difference between no-MBP and MBP group: 19% versus 10% (P = 0.09) and 18% versus 11% (P = 0.69), respectively. Moderate or severe discomfort was reported by 40% of prepared patients. Mortality rate (1.1% vs 3.4%) and mean hospital stay (16 vs 14 days) did not differ significantly between both groups. Conclusions: This first randomized trial demonstrated that rectal cancer surgery without MBP was associated with higher risk of overall and infectious morbidity rates without any significant increase of anastomotic leakage rate. Thus, it suggests continuing to perform MBP before elective rectal resection for cancer. This study is registered with clinicaltrials.gov, number NCT00554892. Copyright © 2010 by Lippincott Williams & Wilkins.