Relationship of injection drug use, antiretroviral therapy resistance, and genetic diversity in the HIV-1 pol gene

Objectives: To determine if a history of injection drug use influences genotypic protease inhibitor (PI) resistance to antiretroviral agents. Methods: We assessed the presence of resistance mutations in Pi-naive injection drug users (IDUs) and non-IDUs participating in the Women's Interagency HIV Study. Eighteen HIV-infected participants who reported injection drug use before study enrollment and 32 HIV-infected non-IDUs contributed a total of 34 and 65 personvisits, respectively, to analyses. Results: Based on data from multiple clones obtained from different time points from each individual, we determined that primary PI resistance mutations were more frequent among person visits contributed by IDUs (24%) than non-IDUs (8%, P = 0.05). Although neither reached statistical significance, diversity was higher within the protease region among study visits carrying Pi-resistant clones at both the nucleotide level (2.66 vs. 2.35; P = 0.08) and at the amino acid level (1.60 vs. 1.32; P = 0.23). Most of the primary resistance mutations could not be detected using the standard population sequencing employed in the clinical setting. Five of 6 individuals in whom clones encoding PI resistance mutations were identified failed Pi-containing highly active antiretroviral therapy within 12 months of therapy initiation. Conclusions: Our findings indicate that more aggressive sampling for resistance mutations among viral clones before highly active antiretroviral therapy initiation might permit selection of more effective treatment, particularly in IDUs. copyright