The Prevalence of Transmitted Resistance to First-Generation Non-Nucleoside Reverse Transcriptase Inhibitors and Its Potential Economic Impact in HIV-Infected Patients

Non-nucleoside reverse transcriptase inhibitor (NNRTI)-based highly active antiretroviral therapy (HAART) including efavirenz is recommended as a 1st-line treatment choice in international HIV guidelines, and it is one of the most common components of initial therapy. Resistance to 1st-generation NNRTIs is found among treated and untreated HIV-infected individuals creating a subpopulation of HIV-infected individuals in whom efavirenz is not fully effective. This analysis reviewed published articles and conference abstracts to examine the prevalence of 1st-generation NNRTI resistance in Europe, the United States (US), and Canada and to identify published evidence of the economic consequences of resistance. The reported prevalence of NNRTI resistance was generally higher in US/Canada than in Europe and increased in both regions from their introduction in the late 1990s until the early 2000s. The most recent time-based trends suggest that NNRTI-resistance prevalence may be stable or decreasing. These estimates of resistance may be understated as resistance estimates using ultra-sensitive genotypic testing methods, which identify low-frequency mutations undetected by standard testing methods, showed increased prevalence of resistance by more than two-fold. No studies were identified that explicitly investigated the costs of drug resistance. Rather, most studies reported costs of treatment change, failure, or disease progression. Among those studies, annual HIV medical costs of those infected with HIV increased 1) as CD4 cells decreased, driven in part by hospitalization at lower CD4 cell counts; 2) for treatment changes, and 3) for each virologic failure. The possible erosion of efficacy or of therapy choices through resistance transmission or selection, even when present with low frequency, may become a barrier to the use of 1st-generation NNRTIs and the increased costs associated with regimen failure and disease progression underlie the importance of identification of treatment resistance to ensure optimal initial therapy choice and regimen succession.