Raltegravir once daily or twice daily in previously untreated patients with HIV-1: a randomised, active-controlled, phase 3 non-inferiority trial.

BACKGROUND: Twice-daily raltegravir with once-daily tenofovir-emtricitabine is an effective initial antiretroviral regimen for patients with HIV-1. On the basis of pharmacokinetic data suggesting efficacy of once-daily raltegravir and because adherence is often improved with once-daily dosing, we aimed to compare these dosing schedules. METHODS: In our international, double-blind, randomised, phase 3 non-inferiority study, we enrolled antiretroviral-naive patients with HIV RNA loads of more than 5000 copies per mL and no baseline resistance to tenofovir or emtricitabine at 83 centres worldwide. We randomly allocated patients (1:1) by use of a computer-generated sequence to receive raltegravir once daily (two 400 mg tablets taken together every 24 h), or twice daily (one 400 mg tablet every 12 h), both in combination with once-daily co-formulated tenofovir 300 mg plus emtricitabine 150 mg. The primary outcome was virological response at 48 weeks (viral RNA loads <50 copies per mL) in patients who received at least one dose of study drug, counting non-completers as failure. We assessed non-inferiority in terms of the proportion of patients in both treatment groups who achieved the primary outcome, with a non-inferiority margin of -10%. This study is registered with ClinicalTrials.gov, number NCT00745823. FINDINGS: From Oct 15, 2008, to Nov 2, 2009, we randomly allocated 775 patients, of whom 382 (99%) of 386 patients in the once-daily group and 388 (99%) of 389 in the twice-daily group received at least one dose of study drug. At baseline, 304 (39%) of 770 treated patients had viral loads of more than 100,000 copies per mL and 188 (24%) had CD4 cell counts of fewer than 200 cells per µL. 318 (83%) of 382 patients in the once-daily group had virological response compared with 343 (89%) of 386 in the twice-daily group (difference -5·7%, 95% CI -10·7 to -0·83; p=0·044). Serious adverse events were reported in 26 (7%) of 382 once-daily recipients and 40 (10%) of 388 twice-daily recipients, and adverse events leading to discontinuation occurred in four (1%) patients in each group. INTERPRETATION: Despite high response rates with both regimens, once-daily raltegravir cannot be recommended in place of twice-daily dosing. FUNDING: Merck.

[Infectious pulmonary complications in HIV-infected patients in the high by active antiretroviral therapy era in Spain]. / Complicaciones infecciosas pulmonares en los pacientes con infección por el virus de la inmunodeficiencia humana en la era del tratamiento antirretroviral de gran actividad en España.

Pulmonary complications in HIV-infected patients are at present a first-rate problem. They are the main cause of hospital admission of these patients in our country. Most HIV-patients have a pulmonary complication during the evolution of the infection. The main etiologic diagnosis is bacterial pneumonia, especially pneumococcal pneumonia; the second most frequent cause is Pneumocystis jiroveci (previously named P. carinii) pneumonia and the third cause is mycobacteriosis, particularly Mycobacterium tuberculosis. From early studies, important changes in the epidemiology of HIV-related pulmonary complications have occurred. General prescription of P. jiroveci primary prophylaxis is probably one of the main causes, and, more recently, the use of highly active antiretroviral therapy may also be an underlying explanation. In this review, epidemiology, diagnosis and outcome of HIV-related pulmonary complications in our country are update.

Complicaciones infecciosas pulmonares en los pacientes con infección por el virus de la inmunodeficiencia humana en la era del tratamiento antirretroviral de gran actividad en España / Infectious pulmonary complications in HIV-infected patients in the high by active antiretroviral therapy era in Spain

Las complicaciones pulmonares en los pacientes con infección por el virus de la inmunodeficiencia humana (VIH) son, actualmente, un problema de primer orden. En España son la primera causa de ingreso hospitalario de estos pacientes. Además, la mayoría experimenta alguna complicación de este tipo durante su evolución. La etiología más frecuente es la neumonía bacteriana, particularmente las producidas por neumococos; en segundo lugar, la neumonías por Pneumocystis jiroveci (anteriormente P. carinii), y en tercer lugar, las micobacterias, sobre todo la tuberculosis. Desde las primeras descripciones de complicaciones pulmonares, su epidemiología ha experimentado cambios notables. Entre las causas principales se encuentra la introducción de la profilaxis primaria frente a P. jiroveci, y más recientemente, la generalización del tratamiento antirretroviral combinado de elevada eficacia. En esta revisión se actualizan las principales causas en la actualidad de complicaciones pulmonares en los pacientes infectados por el VIH en España, su diagnóstico y pronóstico

Pulmonary complications in HIV-infected patients are at present a first-rate problem. They are the main cause of hospital admission of these patients in our country. Most HIV-patients have a pulmonary complication during the evolution of the infection. The main etiologic diagnosis is bacterial pneumonia, especially pneumococcal pneumonia; the second most frequent cause is Pneumocystis jiroveci (previously named P. carinii) pneumonia and the third cause is mycobacteriosis, particularly Mycobacterium tuberculosis. From early studies, important changes in the epidemiology of HIV-related pulmonary complications have occurred. General prescription of P. jiroveci primary prophylaxis is probably one of the main causes, and, more recently, the use of highly active antiretroviral therapy may also be an underlying explanation. In this review, epidemiology, diagnosis and outcome of HIV-related pulmonary complications in our country are update