Decreased darunavir concentrations during once-daily co-administration with maraviroc and raltegravir: OPTIPRIM-ANRS 147 trial

International audienceBackgroundThe OPTIPRIM-ANRS 147 trial compared intensive combination ART (darunavir/ritonavir, tenofovir disoproxil fumarate/emtricitabine, raltegravir and maraviroc) started early during primary HIV-1 infection with standard tritherapy with darunavir/ritonavir, tenofovir disoproxil fumarate and emtricitabine. From month 6 to 18, the percentage of viral load values <50 copies/mL was lower in the pentatherapy arm than in the tritherapy arm. Here we compared antiretroviral drug concentrations between the two arms.MethodsPlasma samples were collected from 50 patients at various times after drug administration. A Bayesian approach based on published population pharmacokinetic models was used to estimate residual drug concentrations (Ctrough) and exposures (AUC) in each patient. A mixed linear regression model was then used to compare the AUC and Ctrough values of each drug used in both groups.ResultsPublished models adequately described our data and could be used to predict Ctrough and AUC. No significant difference in tenofovir disoproxil fumarate, emtricitabine and ritonavir parameters was found between the two arms. However, darunavir Ctrough and AUC were significantly lower in the pentatherapy arm than in the tritherapy arm (P = 0.03 and P = 0.04, respectively).ConclusionsAdding maraviroc and raltegravir to darunavir-based tritherapy decreased darunavir concentrations. Compliance issues, maraviroc–darunavir interaction and raltegravir–darunavir interaction were suspected and may affect the kinetics of viral decay during pentatherapy. A specific pharmacokinetic interaction study is needed to explore the interactions between darunavir and maraviroc and raltegravir

Antimicrobial peptides produced by bacteria: The bacteriocins

Bacteriocins are the subset of antimicrobial peptides (AMPs) produced by bacteria. They are small amphipathic peptides that interact with bacterial membranes leading to cell death. Most of the best known are produced by lactic acid bacteria used as food fermentation starters, because of their potential use as food preservatives. Bacteriocins are divided into two groups: lantibiotics that present posttranslational condensation rings and unmodified peptides. The first are subdivided into elongated versus globular lantibiotics, while four subgroups are recognized among unmodified bacteriocins. The genetic organization is in clusters that may reside into plasmids or transposons, formed by the structural gene, the export and immunity determinants, the quorum sensing governing production and any modification genes. Bacteriocins are active at extremely low concentrations (nM range) due to a dual mode of action: (a) binding to the membrane phospholipids and (b) specific recognition of surface components, both of which collaborate in pore formation. Development of resistance to bacteriocins is very infrequent due to the presence of two targets and is usually due to unspecific modifications of the cell envelope. Bacteriocins are used as food preservatives, either after total or partial purification or as extracts of producing bacteria. In situ production is also used, with the advantage of producing early lysis of the starter bacteria and ripening acceleration of the fermented product. They may also form part of hurdle technologies and be incorporated into packaging systems to allow extended liberation. Medical and veterinary applications are in their infancy but good results have been obtained against infection by Gram-positive bacteria and Helicobacter pylori.Peer reviewe

Human Immunodeficiency Virus Type 1 Group O Infection in France: Clinical Features and Immunovirological Response to Antiretrovirals

International audienc

A highly virulent variant of HIV-1 circulating in the Netherlands.

We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log &lt;sub&gt;10&lt;/sub&gt; increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV-CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences-is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virulence