Diversity of thymidine analogue resistance genotypes among newly diagnosed HIV-1-infected persons

The introduction of highly active antiretroviral therapy (HAART) has resulted in a significant decrease in HIV and AIDS-related mortality and morbidity. However, these treatments can select for drug-resistant viruses which are associated with poor virological responses to the antiretroviral therapy and possible loss of clinical benefit. Drug-resistant viruses can also be transmitted between individuals. In the absence of drug pressure, transmitted drug-resistant viruses gradually lose resistance mutations that confer a selective disadvantage as they evolve to more fit viruses. As a result, unusual resistance-related genotypes not commonly seen in treated patients may arise in the population. Viruses with unique patterns of thymidine analogue-associated mutations (TAMs) have now been identified in a substantial proportion of treatment-naive recently diagnosed persons. In this leading article, I discuss these findings and the potential impact of these unique reverse transcriptase (RT) genotypes on evolution of resistance and treatment responses.