Interaction pharmacocinétique entre l'amprénavir et le ritonavir lors de leur co-administration chez des sujets infectés par le VIH (influence de la glycoprotéine-P?)

CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

Impact écologique des antibiotiques

L'impact de la résistance bactérienne en milieu extra-hospitalier est particulièrement démonstratif pour le pneumocoque. Des études concordantes ont démontré le rôle, à titre individuel, d'une prescription antibiotique antérieure récente et/ou d'une hospitalisation, et, à titre collectif, d e la consommation globale d'antibiotiques dans un pays : plus celle-ci est élevée, comme en France, plus la prévalence d e la résistance est élevée. Une corrélation avec l'échec clinique a été établie pour les macrolides et les fluoroquinolones anti-pneumococciques. Elle est moins clairement établie pour les β-lactamines les plus actives sur le pneumocoque, lorsqu'elles sont prescrites à bonne dose. La baisse de la consommation globale d'antibiotiques est un facteur de décroissance lente de la résistance. L'amoxicilline, à une posologie minimale de 3 grammes par jour, reste le traitement de référence de la pneumonie à pneumocoque en France

Influence du sexe sur la pharmacologie des antirétroviraux

NICE-BU Médecine Odontologie (060882102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Raltegravir Inclusion Decreases CD4 T-Cells Intra-Cellular Viral Load and Increases CD4 and CD28 Positive T-Cells in Selected HIV Patients

Raltegravir (RLT) prevents the integration of HIV DNA in the nucleus, but published studies remain controversial, suggesting that it does not decrease proviral DNA. However, there are only a few studies focused on virus-targeted cells. We aimed our study on the impact of RLT inclusion on total intra-cellular viral DNA (TID) in cellular subsets and immune effects in patients with newly acquired undetectable plasmatic viral load (UVL). Six patients having UVL using an antiretroviral combination for 6 months and CD4 T-cells > 350/mL and <500/mL were selected to receive RLT for 3 months from M0 to M3. Patients had 7 sequential viro-immunological determinations from M-1 to M5. Immune phenotypes were determined by flow cytometry and TID quantification was performed using PCR assay on purified cells. TID (median values) at the initiation of RLT in CD4 T-cells was 117 copies/millions of cells, decreased to 27.5 on M3, and remained thereafter permanently under the cut-off (<10 copies/millions of cells) in 4 out of 6 patients. This was associated with an increase of CD4 and CD4 + CD28+ T-cells and a decrease of HLA-DR expression and apoptosis of CD4 T-cells. RLT inclusion led to decreases in the viral load along with positive immune reconstitution, mainly for CD4 T-cells in HIV patients

Quantitative Immunoassay To Measure Plasma and Intracellular Atazanavir Levels: Analysis of Drug Accumulation in Cultured T Cells

We have developed an enzyme immunoassay to measure atazanavir (ATV) levels in plasma and cells. Anti-ATV polyclonal antibodies were raised in rabbits by using a synthetic ATV derivative coupled to bovine serum albumin as the immunogen, and the enzyme tracer was prepared by chemically coupling the ATV derivative with acetylcholinesterase. These reagents were used to develop a sensitive competitive enzyme immunoassay performed in microtitration plates, and the lowest limit of quantification was 150 pg/ml, which is about 10 times more sensitive than previously published techniques. The plasma assay was performed, after a simple methanol extraction, with a minimum of 30 μl of plasma. This assay showed good precision and efficiency, since the rates of recovery from human plasma and cell extracts spiked with ATV ranged form 93 to 113%, with coefficients of variation of less than 10%. ATV concentrations were measured in peripheral blood mononuclear cells incubated with various ATV concentrations and in CEM cells in the absence or presence of antiretroviral drugs and drug transporter inhibitors. The results indicated a dose-dependent uptake (intracellular concentration/extracellular concentration ratio range, 0.04 to 19). A significant increase in the accumulation of ATV was noticed in the presence of P-glycoprotein and MRP1 inhibitors (dipyridamole, inter alia). Interestingly, efavirenz significantly increased the baseline accumulation of ATV, whereas nevirapine induced a marked reduction. This new enzyme immunoassay for measuring plasma and intracellular ATV levels was fully validated and provides an inexpensive and useful tool for routine therapeutic drug monitoring. Moreover, in vitro results suggested the implication of drug transporters and interactions with other antiviral drugs that should be further explored in human immunodeficiency virus-infected patients

Switch to Ritonavir-Boosted versus Unboosted Atazanavir plus Raltegravir Dual-Drug Therapy Leads to Similar Efficacy and Safety Outcomes in Clinical Practice.

To assess immunovirological response, safety and pharmacokinetic of NRTI-sparing regimen dual therapy of atazanavir (ATV) and raltegravir (RAL) in maintenance strategy.A retrospective analysis was conducted on a cohort of HIV-infected adults followed in French centers (Dat'AIDS cohort), comparing the proportions of virological and therapeutic failures between ATV + RAL and ATV/ritonavir + RAL dual therapy regimens.283 patients were assessed: 185 switched for ATV + RAL and 98 for ATV/ritonavir + RAL dual therapy. Virological failure rate at week 96 was 13.8% (95% CI, 9.8-17.8), without difference between the two groups (Log-rank Test, p = 0.87). The cumulative percentages of patients remaining free of therapeutic failure at week 24, 48 and 96 of dual therapy were 74.9% (95% CI, 69.9-80.0), 65.4% (95% CI, 59.8-70.9) and 53.4% (95% CI, 47.5-59.2), respectively. Four out of 39 confirmed virological failures developed RAL resistance. By multivariate analysis, virological failure was associated with high HIV-1 RNA zenith (p = 0.02), low CD4+ T-cell count at baseline (p<0.001) and short duration on antiretroviral therapy (p<0.001). Before week 96, dual therapy was discontinued in 44 patients (16%) because of various adverse events, with no difference between the two groups. Minimal plasma levels were targeted in 84% and 87% of patients for ATV and RAL, respectively, and both were significantly higher in ritonavir-boosted regimen.Emerging RAL-resistance and discontinuations for adverse events resulted in moderate efficacy rates of ATV and RAL dual therapy in heavily pretreated patients

Successful antiretroviral therapy by using unusual antiretroviral combinations in heavily pre-treated patients: two case reports

In the context of HIV-infected patients with several past antiretroviral therapies and multiple failures, it is possible to be faced with viruses resistant to all drug classes. We report on two HIV-1 infected patients in which the historical genotype showed mutations against all the major drug classes and in which viral suppression has been obtained by non-conventional antiretroviral therapy regimens, including the combination of darunavir at high dosage (800 mg bid), dolutegravir (50 mg bid) and a third agent, i.e. enfuvirtide in the first case and etravirine in the second one

W48 Response Rate of Boceprevir-PegIFN-RBV in Treatment-Experienced HIV Coinfected Patients with HCV genotype 1: ANRS-HC27 BocepreVIH Study

International audienc

Long-term efficacy and toxicity of abacavir/lamivudine/nevirapine compared to the most prescribed ARV regimens before 2013 in a French Nationwide Cohort Study

International audienceData on the long-term efficacy and safety of abacavir/lamivudine (ABC/3TC) and nevirapine (NVP) are scarce. This combination has the advantage of simplifying treatment and improving long-term tolerance. The aim of this study was to compare the rate of any discontinuation of antiretroviral (ARV) regimen because of virologic failure (VF), and/or adverse drug reaction (ADR) among patients receiving stable ARV regimens for at least 6 months.ABC/3TC/NVP was compared to ABC/3TC with either ritonavir-boosted darunavir (DRV/r) or ritonavir-boosted atazanavir (ATV/r), unboosted ATV, or tenofovir/emtricitabine (TDF/FTC) with either one of the following: ATV/r, unboosted ATV, DRV/r, efavirenz (EFV), or NVP, in the French prospective multicenter Dat'AIDS cohort.The study enrolled 16,511 patients treated with following ARV regimens: ABC/3TC/NVP (n = 1089), TDF/FTC/NVP (n = 1542), ABC/3TC/DRV/r (n = 1065), ABC/3TC/ATV/r (n = 1847), ABC/3TC/ATV (n = 563), TDF/FTC/ATV/r (n = 3519), TDF/FTC/DRV/r (n = 2767), TDF/FTC/ATV (n = 419), and TDF/FTC/EFV (n = 3700). Mean follow-up was 36 ± 24 months. Patients treated with ABC/3TC/NVP received this regimen as a switch regimen in 97% of cases. By multivariable analysis, the risk of treatment discontinuation due to VF was similar between ABC/3TC/NVP and other ARV regimens, except for TDF/FTC/ATV and ABC/3TC/ATV, which were associated with a higher risk of treatment interruption due to VF (hazard ratio [HR] 1.99; 95% confidence interval [CI] 1.29-3.06 and HR 2.19; 95% CI 1.51-3.18, respectively). Treatment discontinuation due to ADR was lowest with the ABC/3TC/NVP regimen. Other ARV regimens were associated with a 1.80- to 3.19-fold increase in the risk of treatment discontinuation due to ADR (P < 0.0001 for all comparisons).ABC/3TC/NVP as a simplification regimen is a long-term effective regimen with lower discontinuation due to long-term toxicity compared with other standard ARV regimens