Evaluation and management of early virological failure

To describe the causes, evaluation, and management of early virological failure in patients treated with their first antiretroviral regimen.

Combination antiretroviral therapy predictably induces a rapid virological response, with the majority of patients achieving an undetectable HIV-RNA load by week 24. In clinical trials and cohorts, rates of virological suppression have improved over time. Poor adherence to therapy remains the most common cause of virological failure, and genotype resistance testing is a critical step in evaluating the optimal subsequent approach. Most studies suggest that transient HIV-RNA elevations do not warrant changing treatment, and may be a consequence of laboratory variation. For those who experience virological failure, resistance to individual components of the antiretroviral regimen is dependent on the initial choice of treatment. Once virological failure is confirmed and adherence issues addressed, a prompt change in treatment is warranted to limit the selection of further drug resistance.

Resistance that occurs with early virological failure follows typical patterns, with limited resistance to most antiretroviral agents in the nucleoside reverse transcriptase and protease inhibitor classes. The likelihood of achieving virological suppression with subsequent regimens should be high so long as adherence can be assured.