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Transmitted Drug Resistance Rates Higher with More Sensitive Genotypic Screening: CROI 2014

Current guidelines recommend that patients undergo genotypic resistance testing before initiating antiretroviral therapy due to poorer treatment outcomes being associated with transmitted HIV drug resistance (TDR). Dr. Jeffrey Johnson from division of HIV/AIDS, CDC, presented estimates of transmitted HIV drug resistance using a more sensitive method of genotyping. These newer screening assays are capable of detecting resistant minority variants at levels 10-100 times below detection levels of conventional genotyping. In this study 1070 de-identified HIV+ ARV naïve plasma specimens collected within 3 months of diagnosis were re-analyzed using the more sensitive method to evaluate for additional evidence of transmitted drug resistance, specifically looking at presence of M41L, K103N, Y181C, M184V and K65R. Using conventional methods the prevalence of resistance was: K103N 7%, Y181C 0.8%, M184V 0.3%, M41L 1.1%, K65R 0%, however when applying the sensitive method, all TDR were found to be underestimated. Using the sensitive method, TDR prevalence was: K103N 8.4%, Y181C 2.7%, M184V 1.4%, M41L 1.4% and K65R 1.7%. Overall the conventional method showed 7.9% prevalence of TDR whereas the more sensitive method showed 13.6% drug resistance. When evaluated by geography and demographics, the highest rates of TDR were seen in the west coast (16.9%) and south east regions (17.1%). Age was associated with high rates of TDR with those ages 13-19 having the highest rate of 23.1%. Rates of TDR were also higher among whites and blacks compared with hispanics/latinos. The importance of this study is that providers should be aware that clinically important mutations may be underestimated using conventional genotyping. ART-naïve HIV-infected persons should be closely monitored for treatment failure after initiating antiretroviral therapy.

Li J, Kim D, Linley L, Kline R, Heneine W, Johnson JA. Sensitive screening reveals widespread underestimation of transmitted HIV drug resistance. Abstract 87, CROI 2014, Boston, MA, March 3-6, 2014.

Source: Reporting from Boston for PRN News: Anita Radix, MD