All primary analyses were stratified by cohort Covariates were e

All primary analyses were stratified by cohort. Covariates were excluded if there appeared to be collinearity problems. We accounted for the multiple regimens per patient by applying robust standard error estimation to allow for intragroup correlation. Missing data were included

as a separate category in all analyses. The following sensitivity analyses were Pexidartinib order conducted using multivariate Cox proportional hazards models: separate analyses were conducted for each cohort; for each change in neurocART status a new set of baseline covariates was created; off-cART periods of >90 days were included; all deaths following treatment cessation were excluded; all periods of mono/dual therapy exposures were excluded; and all records with missing CD4 cell counts or Antiinfection Compound Library research buy viral loads were excluded. A sensitivity analysis was also conducted using Poisson regression as opposed to a Cox regression. Secondary analyses were conducted as follows:

neurocART status as a predictor of ‘ADI or death’ within 90 days of cessation of treatment was examined; neurocART as first cART (compared with non-neurocART as first cART) was investigated as a predictor of mortality; CPE score categorized as a four-point variable by quartile (≤6, 7, 8 and ≥9) was investigated as a predictor of mortality; cumulative duration of neurocART use in months prior to the current regimen was also investigated as a predictor of mortality. This was examined as a categorical predictor (never, or 1–9, 10–18 or ≥19 months) with a broad upper category (≥19 months) to avoid fitting to patients

who survived and had extended follow-up, thereby reducing the potential for bias in survival estimates. This model was compared with the model used in the primary analysis using the Akaike information criterion. In these analyses, covariates used were as for the primary analysis. Finally, we also assessed CD4 cell count responses according to neurocART status. Log CD4 cell count was analysed using repeated measures regression, with generalized estimating equations (GEE) methodology, and assumed exchangeable variance structure (but robust calculated variances). CD4 cell counts were recorded for up to 540 days at each 90 days of regimen duration using the closest measurement (taken <90 days before or <30 days after). Additional covariates were included in this analysis: baseline CD4 count (<50, 50–99, 100–199, 200–349 or ≥350 cells/μL or missing), year of cART commencement (1997–1999, 2000–2002 or ≥2003) and time since first cART (≤270, 271–540, 541–810 or >810 days). Data were analysed using stata version 10 (Stata Corporation, College Station, TX, USA). Demographic and clinical characteristics by cohort are summarized in Table 1. A total of 5882 patients were included in these analyses (2384 from AHOD and 3498 from TAHOD), contributing 22 117 patient-years of follow up.

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