Primary HIV-1 Drug-Resistant Minority Variants

Primary HIV drug-resistant mutations are mutations that occur in an HIV-infected individual prior to the initiation of antiretroviral therapy. These mutations may arise by de novo mutagenesis or result from transmission. Drug-resistant mutations may reduce the effectiveness of antiretroviral therapy, leading to inadequate virological outcomes. Currently, Sanger sequencing is the standard method for detection of drug-resistant mutations to inform treatment decisions, but it does not detect minor variant mutations. Drug-resistant minority variants can be detected by next generation sequencing. However, several challenges, including cost of infrastructure and the need for complex data analysis bioinformatics tools, remain major setbacks for next generation sequencing use. More importantly, the clinical impact of drug-resistant minority variants on antiretroviral therapy is not well understood, underscoring the importance for understanding whether the levels of primary drug-resistant minority variants for different mutations impact on the effectiveness of antiretroviral therapy and the rationale for inclusion in routine diagnostics. Understanding the impact of primary drug-resistant minority variants will help inform how next generation sequencing may be utilized in the future for pre-emptive clinical antiretroviral therapy decision making.