Using mechanistic models to simulate comparative effectiveness trials of therapy and to estimate long-term outcomes in HIV care.
BACKGROUND
In HIV care, it is difficult to decide when to initiate therapy, which drugs to use for initial treatment, and which drugs to use if drug resistance develops. With hundreds of possible drug regimens available and variable patterns of drug resistance, randomized controlled trials cannot answer all HIV treatment decisions. Mechanistic models of HIV infection can be used to conduct virtual therapeutic trials with the goal of predicting outcomes, some of which are long-term and may not fall within the time frame of a typical therapeutic trial.


METHODS
We used a previously developed and validated model of HIV infection to replicate 2 arms of an HIV initial treatment trial (ACTG A5142) and predict long-term outcomes. The model incorporated data about biologic processes involved in the development of drug resistance.


RESULTS
The model reproduced the proportion that developed AIDS (0.04 and 0.05 for the efavirenz arm and lopinavir arms, respectively, vs. 0.04 and 0.06 for the trial), the development of virologic failure (0.27 and 0.33 for the Efavirenz arm and lopinavir arms, respectively, vs. 0.24 and 0.37 for the trial), and drug resistance. The hazard ratio for the time to treatment failure, a combination of resistance and other causes (0.96 for the model vs. 0.75 for the trial; 95% confidence interval, 0.57-0.98), and changes in CD4 cell count, were less accurate. The model estimated longer-term life expectancy, quality-adjusted life expectancy, and HIV-related deaths.


CONCLUSIONS
Mechanistic models of HIV infections have the potential to be useful in comparative effectiveness research.
Roberts
Mark S
MS
Department of Health Policy and Management, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA. mroberts@pitt.edu
Nucifora
Kimberly A
KA
Braithwaite
R Scott
RS
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000401:mortality; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D002986:Clinical Trials as Topic; D057186:Comparative Effectiveness Research / Q000379:methods* / Q000706:statistics & numerical data*; D003198:Computer Simulation; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D008017:Life Expectancy; D015233:Models, Statistical; D011788:Quality of Life; D013997:Time Factors; D016896:Treatment Outcome
D044966:Anti-Retroviral Agents
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