Assessing resistance costs of antiretroviral therapies via measures of future drug options.

Abstract

The emergence of drug-resistant human immunodeficiency virus (HIV) type 1 in the setting of antiretroviral therapy failure limits the number of drugs available for use in subsequent therapy regimens. To quantify the relative HIV-1-resistance costs associated with various antiretroviral therapy strategies, we developed 2 related measures of future drug options (FDOs) by use of rule-based genotype-interpretation systems. The FDO1 metric assesses the number of drug classes that remain useful; the FDO2 metric assesses the number of drug classes that remain useful and the number of active drugs within each class. Application of these methods is illustrated with data from a randomized study of 3 therapy regimens in nucleoside analog-experienced patients. Each therapy regimen resulted in a unique pattern of drug-resistance (and cross-resistance) mutations. The regimen with the highest virologic failure rate preserved greater future drug options. Quantification of future drug options as an outcome of antiretroviral therapy trials may complement traditional clinical, virologic, and immunologic end points, thereby providing novel insights.