Long-acting cabotegravir plus rilpivirine for treatment in adults with HIV-1 infection: 96-week results of the randomised, open-label, phase 3 FLAIR study.

BACKGROUND: There is a need for more convenient, less frequent treatment to help address challenges associated with daily oral HIV treatment in people living with HIV, including stigma, pill burden, drug-food interactions, and adherence. The phase 3 ATLAS and FLAIR studies showed non-inferiority of long-acting cabotegravir and rilpivirine dosed every 4 weeks compared with standard oral therapy for the maintenance of virological suppression in adults with HIV-1 over 48 weeks. We present the 96-week findings. METHODS: FLAIR is a randomised, phase 3, open-label, multicentre study done in 11 countries investigating whether switching to long-acting cabotegravir and rilpivirine is non-inferior to daily dolutegravir, abacavir, and lamivudine in virologically suppressed adults living with HIV-1. Antiretroviral therapy (ART)-naive participants received induction therapy with daily oral dolutegravir (50 mg), abacavir (600 mg), and lamivudine (300 mg) for 20 weeks. After 16 weeks, participants with less than 50 HIV-1 RNA copies per mL were randomly assigned (1:1) to continue the standard of care regimen (standard care group) or switch to receive daily oral cabotegravir 30 mg and rilpivirine 25 mg for at least 4 weeks followed by long-acting cabotegravir 400 mg and rilpivirine 600 mg, administered as two 2 mL intramuscular injections, every 4 weeks for at least 96 weeks (long-acting group). Randomisation was stratified by baseline (preinduction) HIV-1 RNA (<100 000 or ≥100 000 copies per mL) and sex at birth and used GlaxoSmithKline-verified randomisation software (RandAll NG, version 1.3.3) for treatment assignment. The primary endpoint was the proportion of participants with plasma HIV-1 RNA of 50 copies per mL or more assessed as per the US Food and Drug Administration (FDA) Snapshot algorithm at week 48, which has been reported previously. Here, we report the proportion of participants with 50 or more HIV-1 RNA copies per mL using the FDA Snapshot algorithm at week 96 (intention-to-treat population; non-inferiority margin 6%). The trial is registered with ClinicalTrials.gov, NCT02938520. FINDINGS: Between Oct 27, 2016, and March 24, 2017, 809 participants were screened. 631 (78%) participants entered the induction phase and 566 (70%) were randomly assigned to either the standard care group (283 [50%] participants) or the long-acting group (283 [50%]). Median age was 34 years (IQR 29 to 43), 62 (11%) were 50 years or older, 127 (22%) were women (sex at birth), and 419 (74%) were white. At week 96, nine (3%) participants in each arm had 50 or more HIV-1 RNA copies per mL, with an adjusted difference of 0·0 (95% CI -2·9 to 2·9), consistent with non-inferiority established at week 48. Across both treatment groups, adverse events leading to withdrawal were infrequent (14 [5%] participants in the long-acting group and four [1%] in the standard care group). Injection site reactions were the most common adverse event, reported by 245 (88%) participants in the long-acting group; their frequency decreased over time. Median injection site reaction duration was 3 days (IQR 2 to 4), and 3082 (99%) of 3100 reactions were grade 1 or 2. No deaths occurred during the maintenance phase. INTERPRETATION: The 96-week results reaffirm the 48-week results, showing long-acting cabotegravir and rilpivirine continued to be non-inferior compared with continuing a standard care regimen in adults with HIV-1 for the maintenance of viral suppression. These results support the durability of long-acting cabotegravir and rilpivirine, over an almost 2-year-long period, as a therapeutic option for virally suppressed adults with HIV-1. FUNDING: ViiV Healthcare and Janssen Research and Development.

La leishmaniasis visceral en la región de Murcia: estudio multicéntrico 1997-2013 / Visceral leishmaniasis in Murcia: Multicentric study 1997-2013

Introducción: La prevalencia de la leishmaniasis visceral (LV), una parasitosis endémica en la cuenca mediterránea, puede verse afectada por movimientos migratorios. Objetivo: El objetivo de este estudio fue analizar los casos de LV valorados en hospitales de la región de Murcia. Material y métodos: Se trata de un estudio retrospectivo multicéntrico de los casos de LV diagnosticados y tratados en los diferentes hospitales de nuestra región, que se agruparon en 2 cohortes: período A (pA), el comprendido entre los años 1997 y 2005, y período B (pB), el transcurrido entre 2006 y 2013. Resultados: Se analizaron 97 casos de LV (75% fueron hombres y la edad media fue de 35 años), 36 en pA y 61 en pB; el 11% de los pacientes procedían de otros países en pA y el 22% en pB (subsaharianos en 10 casos); el 55% tenían algún tipo de inmunosupresión (80% de ellos estaban diagnosticados de infección por VIH). Las manifestaciones más frecuentes fueron: fiebre (85%) y astenia (66%). La duración media de los síntomas antes de la primera consulta fue de 47 días, y el tiempo medio transcurrido entre esta primera consulta y la realización de la prueba diagnóstica, de 13 días. El hallazgo más común en la exploración física fue la esplenomegalia (89%), mientras que la trombocitopenia fue el hallazgo de laboratorio más constante (78%). El diagnóstico se confirmó con la detección de amastigotes y/o PCR del aspirado medular en el 61% de los casos; en el 39% restante el aspirado fue negativo y fue necesario el estudio de otras muestras (biopsia de médula ósea, ganglio linfático, laringe, colon, parótida y amígdala, PCR en sangre, serología o inmunocromatografía en orina). El tratamiento más usado fue anfotericina B liposomal (71%), seguida de glucantime (27%) y anfotericina B complejo lipídico (1%); en un caso no se pudo averiguar el tratamiento administrado. Se objetivaron 16 recidivas, 11 de ellas en pacientes con sida. Conclusiones: Aun a riesgo de sesgos propios de estudios retrospectivos y a pesar del mejor control de la infección VIH, observamos en nuestra región un aumento en la frecuencia de casos de LV, probablemente favorecido por el aumento del número de inmigrantes.

Introduction: The prevalence of visceral leishmaniasis (VL), an endemic parasitic infection in the Mediterranean basin, can be affected by migratory movements. Objective: To analyze VL cases evaluated at several hospitals in the Murcia region. Methods: Retrospective, multicentric study of VL cases; patients were grouped into two time periods: period A (pA: 1997-2005) and period B (pB: 2006-2013). Results: A total of 97 VL cases were analyzed (75% men, mean age 35 years), 36 of them in pA and 61 in pB; 11% and 22% of the patients were foreigners in pA and pB, respectively (10 from sub-Saharan Africa); 55% suffered from some type of immunosuppression (80% HIV). The most common clinical manifestations were fever (85%) and asthenia (66%). The mean duration of symptoms before the first medical contact was 47 days and the average time between the first contact and the microbiological confirmation was 13 days. The most common finding on physical examination was splenomegaly (89%), whereas thrombocytopenia was the most frequent laboratory finding (78%). Diagnoses were confirmed by detection of amastigotes and/or PCR of bone marrow aspiration (BMA) in 61%; in the remaining 39% of cases, BMA was negative and additional samples were necessary (bone marrow, lymph node, larynx, colon, parotid and amygdala biopsy, PCR of blood samples, serology or urine antigen detection). The most commonly used treatment was liposomal amphotericin B (71%), followed by glucantime (27%) and amphotericin B lipid complex (1%). A total of 16 recurrent cases (11 in AIDS patients), were bserved. Conclusions: Although this is a retrospective study and despite better control of HIV infection, we have observed an increase in the frequency of VL cases in our region, which is probably related to migratory flows.

Prevention of recurrences in patients with lone atrial fibrillation. The dose-dependent effect of angiotensin II receptor blockers.

BACKGROUND: Atrial fibrillation (AF) leads to the activation of the renin-angiotensin system (RAS), which seems to play an important role in atrial remodelling. It is not known yet whether RAS blockade may prevent recurrences in patients with lone AF. METHODS AND RESULTS: Patients with an episode of persistent AF for >7 days, in the absence of cardiac or extracardiac causes and with normal blood pressure values (lone AF), were recruited. Ninety patients were randomised and scheduled for electrical cardioversion. Three groups of patients were compared: Group I was treated with amiodarone 400 mg daily (30 patients), group II was treated with amiodarone 400 mg daily plus irbesartan 150 mg daily (30 patients) and group III with amiodarone 400 mg daily plus irbesartan 300 mg daily (30 patients). The primary endpoint was the time to a first recurrence of AF. The patients were cardioverted and followed. The Kaplan-Meier analysis of time to first recurrence during the follow-up period showed that patients treated with amiodarone 400 mg plus irbesartan 300 mg had a greater probability of remaining free of AF (77% vs. 52% for amiodarone and 65% for amiodarone+irbesartan 150 mg), hazard ratio for a recurrence in group III: 0.47 (95% CI 0.27-0.82; p=0.001). CONCLUSIONS: The combination of irbesartan plus amiodarone decreased the rate of AF recurrences, with a dose-dependent effect, in lone AF patients.