BCR/ABLindependent resistance mechanisms include processes that affect drug delivery

BCR/ABLindependent resistance mechanisms include processes that affect drug delivery

inked with epidemiological and antiretroviral treatment data in a large resistance study in Germany including ART naive PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19663632 as well as treated GSK-126 patients in order to estimate the proportion of transmitted and acquired HIV drug resistance. amino acid substitutions and to determine drug susceptibility. For epidemiological analysis, HIV sequences isolated from ART naive patients were analysed using the surveillance HIV drug resistance mutation list, SDRM. Only the first HIV genotypic resistance test per patient while treatment naive was considered for the estimation of the prevalence of TDR. HIV sequences isolated from ART experienced patients were analysed using the mutation list of the International Antiviral Society-USA, IAS, 2011. Overall ADR was estimated by including one HIV sequence/patient/year from antiretroviral treatment experienced patients. For the estimation of ADR within different drug classes only viral sequences of patients treated with the respective drug class were considered. HIV subtype on patient level was assigned based on the first available viral sequence of a patient centrally using the REGA HIV-1 Subtyping Tool – Version 2.0. Statistical analysis Viral sequences available between 1998 and 2011 were collected and analysed. For the estimation of trends in the proportion of HIV drug resistance over time viral sequences sampled between 2001 and 2011 were included into the analyses. The characteristics of patients with available sequences compared to those who were not genotyped were compared with simple logistic regression. Patients and viral sequences were categorised into ART naive and treatment experienced. Viral sequences were considered to originate from treatment naive patients in case of ART start 15 days prior to the date of resistance testing, to account for delays in the documentation of the date of resistance testing results and the actual date of blood sampling. The time between resistance testing and antiretroviral treatment start and the proportion of patients with resistance test before ART start were analysed by using data from patients with documented firstline treatment start. The proportion of patients with antiretroviral treatment failure undergoing resistance testing was calculated for patients with first line treatment start in one of the resistance study centres who had.180 days of treatment experience and a resistance test within 90 days after virologic failure. Virologic failure was defined as two consecutive viral load measurements with.50 copies/ml within 180 days or one viral load measurement with.1000 copies/ml. For different drug classes the proportion of cumulative ART exposure per year, the median days of previous ART exposure and the proportion of patients showing history of exposure to the respective drug class were calculated, excluding treatment interruption time. A simple linear regression was performed on the duration of antiretroviral treatment exposure in days prior to resistance testing with increasing year of genotyping for different drug classes and on the total treatment exposure. In a univariate analysis of factors associated with HIV drug resistance the following covariates were separately included: age, gender, transmission group category, HIV subtype, ART interruption, duration of previous ART exposure, CD4 cell count, and plasma viral load at the time point of testing or 30 days prior to or 15 days after testing, year of resistance test at documented ART start. Factors signi

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