Modelling the association between adherence and viral load in HIV-infected patients.
The primary objective of this paper is to investigate the effect of adherence to prescribed antiretroviral therapy on virologic response measured repeatedly over time in HIV-infected patients. To this end observations on plasma viral load (HIV RNA) assessed in copies/ml are categorized into four clinically meaningful states, [0--50[, [50--400[, [400--2000[, [2000 and up. A time-dependent continuation ratio model is used to analyse longitudinal ordinal responses. The main challenge lies in modelling dependencies over time and using information contained in the data efficiently to establish a dynamic relation between observed patient adherence and viral load. Among the several measures of adherence investigated, two specifically account for long periods of time without intake. One is derived from the third moment of the inter-dose interval distribution, while the second reflects internal drug exposure using pharmacokinetic parameters. The approach is applied to a clinical trial involving 35 patients who were followed over 12 months. Results demonstrate a significant relation between patient adherence and virologic response.
Vrijens
Bernard
B
Department of Applied Mathematics and Computer Science, University of Ghent, Belgium. bernard.vrijens@aardex.net
Goetghebeur
Els
E
de Klerk
Erik
E
Rode
Richard
R
Mayer
Steve
S
Urquhart
John
J
D005260:Female; D006678:HIV / Q000254:growth & development*; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D006801:Humans; D008137:Longitudinal Studies; D015233:Models, Statistical; D010349:Patient Compliance; D012367:RNA, Viral / Q000097:blood; D016032:Randomized Controlled Trials as Topic; D019562:Viral Load
D017320:HIV Protease Inhibitors; D012367:RNA, Viral