Long-acting intramuscular cabotegravir and rilpivirine in adults with HIV-1 infection (LATTE-2): 96-week results of a randomised, open-label, phase 2b, non-inferiority trial

Background Cabotegravir and rilpivirine are antiretroviral drugs in development as long-acting injectable formulations. The LATTE-2 study evaluated long-acting cabotegravir plus rilpivirine for maintenance of HIV-1 viral suppression through 96 weeks. Methods In this randomised, phase 2b, open-label study, treatment-naive adults infected with HIV-1 initially received oral cabotegravir 30 mg plus abacavir–lamivudine 600–300 mg once daily. The objective of this study was to select an intramuscular dosing regimen based on a comparison of the antiviral activity, tolerability, and safety of the two intramuscular dosing regimens relative to oral cabotegravir plus abacavir–lamivudine. After a 20-week induction period on oral cabotegravir plus abacavir–lamivudine, patients with viral suppression (plasma HIV-1 RNA 90%). Difference in proportions and associated 95% CIs were supportive to the primary analysis. The trial is registered at ClinicalTrials.gov, number NCT02120352. Findings Among 309 enrolled patients, 286 were randomly assigned to the maintenance period (115 to each of the 4-week and 8-week groups and 56 to the oral treatment group). This study is currently ongoing. At 32 weeks following randomisation, both long-acting regimens met primary criteria for comparability in viral suppression relative to the oral comparator group. Viral suppression was maintained at 32 weeks in 51 (91%) of 56 patients in the oral treatment group, 108 (94%) of 115 patients in the 4-week group (difference 2·8% [95% CI −5·8 to 11·5] vs oral treatment), and 109 (95%) of 115 patients in the 8-week group (difference 3·7% [−4·8 to 12·2] vs oral treatment). At week 96, viral suppression was maintained in 47 (84%) of 56 patients receiving oral treatment, 100 (87%) of 115 patients in the 4-week group, and 108 (94%) of 115 patients in the 8-week group. Three patients (1%) experienced protocol-defined virological failure (two in the 8-week group; one in the oral treatment group). Injection-site reactions were mild (3648 [84%] of 4360 injections) or moderate (673 [15%] of 4360 injections) in intensity and rarely resulted in discontinuation (two [<1%] of 230 patients); injection-site pain was reported most frequently. Serious adverse events during maintenance were reported in 22 (10%) of 230 patients in the intramuscular groups (4-week and 8-week groups) and seven (13%) of 56 patients in the oral treatment group; none were drug related. Interpretation The two-drug combination of all-injectable, long-acting cabotegravir plus rilpivirine every 4 weeks or every 8 weeks was as effective as daily three-drug oral therapy at maintaining HIV-1 viral suppression through 96 weeks and was well accepted and tolerated. Funding ViiV Healthcare and Janssen R&D

ESTIMACIÓN DEL CONSUMO DE PASTO ESTRELLA (Cynodon plectostachyus K. Schum.) POR VACAS LECHERAS EN PASTOREO MEDIANTE LAS TÉCNICAS DE N-ALCANOS, DIFERENCIA EN MASA FORRAJERA Y COMPORTAMIENTO AL PASTOREO

El objetivo de este trabajo fue comparar tres técnicas para estimar el consumo de materia seca (CMS) de pasto estrella por vacas lecheras en pastoreo: n alcanos, diferencia en masa forrajera y comportamiento al pastoreo. Para ello, se realizaron dos experimen tos con un diseño experimental de cuadrado latino 4 x 4 . En ambos experimentos se proporcionó 6 kg de un concentrado constituido de 8 1 % de maíz molido, 10 % de canola, 7 % de melaza y 2 % de urea más 0, 600, 900 y 1200 g de pulpa de café para cada tratamiento , respectivamente . En el experimento uno no existieron diferencias en el CMS de pasto estrella (P>0.05) entre n alcanos y diferen cia en masa forrajera con 2.9 y 3.3 kg de materia seca (MS) vaca 1 día 1 . En el segundo experimento no existieron diferencias (P>0.05) entre n alcanos y comportamiento al pastoreo en la estimación del CMS del pasto estrella con 6.7 y 6.3 kg de MS vaca 1 dí a 1 . Los n alcanos y diferencia en masa forrajera se relacionaron bien en el primer experimento (r 2 =0.80) y en el segundo experimento, los n alcanos y comportamiento al pastoreo presentaron una relación baja con un r 2 de 0.42. Se concluyó que la técnica de n alcanos , fue la más precisa para conocer el consumo de pasto estrella, de vacas en pastoreo , y que las técnicas de comportamiento al pastoreo y por diferencia en masa forrajera resultaron menos precisas . L a adición de pulpa de café entre 15 y 20% no a fect ó el consumo de pasto estrella en vacas lecheras , por lo que el empleo de este subproducto es recomendable para reducir los costos de alimentación del ganado lechero

A novel approach to study the morphology and chemistry of pollen in a phylogenetic context, applied to the halophytic taxon Nitraria L.(Nitrariaceae)

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Glucocorticoids suppress bone formation by attenuating osteoblast differentiation via the monomeric glucocorticoid receptor

Development of osteoporosis severely complicates long-term glucocorticoid (GC) therapy. Using a Cre-transgenic mouse line, we now demonstrate that GCs are unable to repress bone formation in the absence of glucocorticoid receptor (GR) expression in osteoblasts as they become refractory to hormone-induced apoptosis, inhibition of proliferation, and differentiation. In contrast, GC treatment still reduces bone formation in mice carrying a mutation that only disrupts GR dimerization, resulting in bone loss in vivo, enhanced apoptosis, and suppressed differentiation in vitro. The inhibitory GC effects on osteoblasts can be explained by a mechanism involving suppression of cytokines, such as interleukin 11, via interaction of the monomeric GR with AP-1, but not NF-kappaB. Thus, GCs inhibit cytokines independent of GR dimerization and thereby attenuate osteoblast differentiation, which accounts, in part, for bone loss during GC therapy