AZD1152-HQPA Barasertib Subjects and design We conducted a multicentre observational study

special relevance considering that treatment adherence is the main factor to achieve viral suppression and that, despite the advances in drug development, treatment failures attributable to suboptimal adherence continue to occur. Thus, more convenient and better tolerable regimens AZD1152-HQPA Barasertib are still needed for the improvement of patient adherence and to maintain longterm virological suppression. Methods Subjects and design We conducted a multicentre observational study of all consecutive treatment experienced HIV 1 infected adult patients, on failing antiretroviral therapy who started a dual therapy rescue regimen including a PI/r, between January 2005 and September 2011 in three university affiliated hospitals in Barcelona, Spain. Patients were identified through a systematic search of the HIV database at each centre.
The antiretroviral drug combinations were selected by clinicians AG-490 EGFR inhibitor in charge of patients, on the basis of the cumulative resistance profile, based on all available genotypic resistance tests for each patient, the individual history of antiretroviral treatment and the particular characteristics of adherence and tolerance of each patient. Demographic data and HIV related data were recorded for each patient. HIV 1 RNA measurements, CD4 T cell counts, haematology, liver function tests, hepatitis C virus and hepatitis B virus serostatus, fasting blood lipid and clinical evaluations were recorded at baseline and 12, 24, 48, 72 and 96 weeks thereafter. Adherence was evaluated according to the information available in medical records. Genotypic resistance tests were performed using the vircoTYPE HIV1 test.
Drug RAMs were as defined by the International AIDS Society USA guidelines.15 The number of active drugs in each regimen was calculated according to the Stanford HIV Resistance Database interpretation algorithm : 1, 0.5 or 0 points were assigned to each drug in the regimen, depending on whether it had low level/zero resistance, intermediate resistance or highlevel resistance, respectively.16 Brivanib alaninate Raltegravir was considered to be fully active in patients with no previous failure to this drug, and maraviroc was considered fully active in the case of CCR5 tropism, as determined with the Enhanced sensitivity phenotypic Trofilew assay.
Efficacy and safety assessments The efficacy was evaluated as the percentage of patients remaining free of therapeutic failure as evaluated by a time to treatment failure algorithm using intent to treat analysis, in which virological failure, missing values and discontinuation for any reason were recorded as therapeutic failure.17 An on treatment analysis was also conducted, in which permanent interruptions of therapy, missing values or switches were censored. Virological failure was defined as never achieving a plasma viral load,50 copies/mL or having two consecutive determinations of HIV RNA.50 copies/mL at week 24 or later. Safety and tolerability were assessed on the basis of clinical and laboratory adverse events. WHO toxicity grading scales were used to characterize abnormalities in analytical results and physical examination.18 The number of adverse events leading to drug discontinuation was recorded. Mean changes in CD4 T cell counts and fasting blood lipids over time were also evaluated. Statistical analysis SP