Pharmacokinetics of once-daily lopinavir/ritonavir and the influence of dose modifications.

Contains fulltext : 49125.pdf (publisher's version ) (Closed access)We studied the pharmacokinetics of lopinavir/ritonavir dosed at 800/200 mg a day in 20 HIV-1-infected patients, and evaluated the effect of dose modifications in the case of trough concentration (Ctrough) levels less than 1.0 mg/l. Ctrough levels after the daily administration of lopinavir/ritonavir were lower than with twice daily administration. Dose modifications in four patients with Ctrough levels less than 1.0 mg/l succeeded in only one patient. Therapeutic drug monitoring can identify patients with lower-than-expected lopinavir exposure in a larger study

Efficiency of the male effect with photostimulated bucks does not depend on their familiarity with goats

Remerciements : Inra, UMR PRC, Plateforme de Phénotypage - Endocrinologie, 37380 NouzillyIn ewes, the ovulatory response of females exposed to familiar rams is lower than the response of those exposed to novel ones. In goats, males rendered sexually active by exposure to long days are more efficient to induce ovulation in seasonal anestrous females than untreated males. Two experiments were conducted to determine 1) whether male goats remain familiar to females after 45 days of separation; and 2) whether photostimulated males are able to stimulate the sexual activity of females, independently of their familiarity with them. In experiment 1, three groups of goats (n = 10 goats per group) were put in contact with males (n = 2 per group) during 10 days in November (familiarization period). These males were called familiar males. After 15, 30 and 45 days of separation from the males, females of each group were exposed to familiar or novel males during 10 min. In each test, goats in contact with novel males displayed more distress bleats, escapes, head butts, and sniffing than those in contact with familiar males (P < 0.05). In experiment 2, we used sexually inactive (n = 4 control males), and sexually active males (n = 4 photostimulated males). In February, two groups of goats (n = 50 each) were put in contact with control or photostimulated males (n = 2 each) during 10 days (“familiar” control or photostimulated male, respectively). After 45 days of separation from the males, both groups of females were further divided into two groups (n = 25 goats per group). In April, two groups were re-exposed to “familiar” control or “familiar” photostimulated males (n = 2 per group), whereas the other two groups were exposed to “novel” control or “novel” photostimulated males (n = 2 per group). The photostimulated males displayed a higher level of sexual behavior than the controls. The proportion of goats that ovulated and displayed estrus was higher when exposed to the photostimulated males than when exposed to control ones (≥ 80% vs. 0%; P < 0.05). These proportions did not differ between groups exposed to familiar or novel photostimulated males (P > 0.05). We concluded that after 45 days of separation, males are still familiar to females. The photostimulated males are able to induce the sexual activity of seasonally anestrous goats independently of their familiarity with them

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 <sub>10</sub> 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