Factors associated with different responses to combination antiretroviral therapy in an observational cohort study of HIV-1 infected patients.
Doctoral thesis, UCL (University College London).
The introduction of combination antiretroviral therapy (cART) into clinical practice for the treatment of HIV in 1995-1996 has led to dramatic reductions in mortality and morbidity. Factors linked to a positive response to therapy include a potent and tolerable regimen, good adherence and low levels of HIV drug resistance. The aims of this thesis were to investigate factors potentially associated with different responses to cART measured using virological and immunological predictive markers, and also to look at the development of toxicities to a specific regimen. The analyses were based on data from the EuroSIDA study, which is an observational cohort of 14,310 HIV-1 infected patients from Europe, Israel and Argentina. Data collected includes demographic history, CD4 cell counts, viral loads and details of all drugs taken. EuroSIDA also collects viral sequence data for its resistance database. Investigation into virological response to first-line cART across geographical regions found evidence of variation, which was most apparent in early-cART years. Virological response improved over calendar time in all regions, especially in East Europe. Neither HIV-1 subtype nor transmitted drug resistance (TDR) were found to be associated with virological response to cART, however statistical power was limited. A significantly decreased risk of virological failure was found in patients starting efavirenz compared with nevirapine, which did not appear to be explained by baseline drug resistance. Finally, incidence of abacavir discontinuation due to a hypersensitivity reaction side effect of the drug appeared to be higher in patients starting abacavir as part of first-line therapy but decreased in recent years. In conclusion, this thesis has compared a variety of different responses to antiretroviral therapy across subsets of a large heterogeneous population. It is hoped that these findings will contribute to research in monitoring trends in response to therapy and provide insight into association with the genetic variability of the virus.
|Title:||Factors associated with different responses to combination antiretroviral therapy in an observational cohort study of HIV-1 infected patients|
|Open access status:||An open access version is available from UCL Discovery|
|Additional information:||Third party copyright material has been removed from this thesis.|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health Care > Primary Care and Population Health|
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