Associations antifongiques dans les infections fongiques invasives

International audienceInvasive fungal infections (candidiasis, aspergillosis and cryptococcosis) are major complications in immunocompromised patients and account for high morbidity and mortality. Guidelines on first-line therapy of invasive fungal infections are based on randomised clinical trials or experts’ guidelines and include essentially single antifungal therapies, except for cryptococcosis. However, the severe prognosis of these infections raises the interest of antifungal associations, in first line or second-line therapy, and many experimental data have been published on this issue. In humans, amphotericin B plus flucytosine combination therapy in cryptococcal meningitis has been largely validated, especially in HIV-infected patients. Also, a few studies demonstrated that the combination of fluconazole plus amphotericin B in candidiasis is not antagonistic and that caspofungin plus polyene or caspofungin plus azole combinations may be beneficial in invasive aspergillosis. Randomised studies are necessary to confirm these data. A study assessing anidulafungin plus voriconazole association in aspergillosis is oncoming.Les mycoses invasives (candidoses, aspergilloses et cryptococcoses) sont des complications infectieuses fréquentes d’une immunodépression, responsables d’une importante morbimortalité. Leur traitement de première ligne bénéficie de recommandations thérapeutiques qui sont basées selon les pathologies sur des essais randomisées ou sur des avis d’experts, et sont constituées essentiellement de monothérapies antifongiques, sauf pour la cryptococcose. Mais la sévérité de ces infections et l’existence de nombreux travaux expérimentaux et cliniques sur le sujet soulèvent la question de l’apport des bithérapies antifongiques, en traitement d’attaque ou de seconde ligne. Dans la cryptococcose neuroméningée, l’association amphotéricine B plus flucytosine a été bien validée dans des études randomisées, notamment chez les patients séropositifs pour le VIH. Dans les candidémies, des études démontrent l’absence d’antagonisme de l’association fluconazole plus amphotéricine B. Dans l’aspergillose, de rares études cliniques suggèrent, malgré des limites méthodologiques, un bénéfice des associations caspofungine plus polyène ou caspofungine plus azolé. Mais des études randomisées sont encore nécessaires pour démontrer le bénéfice de ces dernières associations. Une étude évaluant l’association anidulafungine plus voriconazole dans le traitement des aspergilloses invasives devrait débuter prochainement

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 log10 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

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