title: Dynamic treatment model to examine the association between phenotypic drug resistance and duration of HIV viral suppression.
abstract: Recent advances in the chemotherapy of HIV infection have been successful in delaying the progression of disease in many patients and are responsible for the decline in HIV-related deaths in the United States. Yet, there are many patients who fail to maintain suppressed viral loads on treatment. Means to extend the utility of currently available drugs include developing improved ways to assess the therapeutic impact of drug-resistant variants. A mathematical model to incorporate the presence of resistance mutations with either primary or secondary classifications is created as a means to explore the association between phenotypic resistance and duration of viral response to therapy. The model, which includes phenotypic and genotypic resistance information for each viral mutant, is presented here with a simplified five-codon genome. However, as additional experimental data and computational resources become available future users may adapt the model to be larger and more accurate. Secondary analyses suggest that, in this model, the resistance phenotypes of the strains with an intermediate number of mutations are the primary determinants of both the total duration of viral suppression with a single treatment and the difference between the durations of suppression of the forward and reverse sequential administrations of two treatments. These findings imply that a model including the resistance phenotype and in vivo response of genotypically-resistant viral strains may lead to a priori prediction of successful anti-HIV drug selection for an individual harboring drug-resistant virus.
authors: Department of Biostatistics, University of California, P.O. Box 951772, Los Angeles, CA 90095-1772, USA. snedecor@cop.ufl.edu
authors: Sonya J
authors: SJ
authors: Snedecor
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D006678:HIV / Q000235:genetics*; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008954:Models, Biological; D009154:Mutation; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents