Abstract

Protease inhibitor (PI) resistance-associated mutations (RAMs) are commonly observed in PI-naive patients who are infected with HIV-1 subtype A/E. Few data are available on the genetic mechanisms of PI resistance in non-B HIV-1. This study was aimed to compare PI-RAMs between PI-naive and -experienced patients and determine PI resistance in each group. Genotypic resistance testing was conducted among a cohort of HIV-1-infected patients who were diagnosed with virologic failure. We studied 137 patients of whom 75 patients were in PI-naive group and 62 patients in PI-experienced group. Median CD4 cell count and HIV-1 RNA at virologic failure were 169 cells/mm3 and 14,100 copies/mL, respectively. The clinical characteristics between 2 groups were similar (p > 0.05) except for the duration of antiretroviral therapy (ART) which was shorter in PI-naive group (31.5 vs 46.8 months, p=0.028). Proportion of patients with primary PI-RAMs was 2.7% in PI-naive and 19% in PI-experienced groups (p=0.002). The most common primary PI-RAMs in the latter group were V82A (10%), I54V (7%) and G48V (4.8%). Proportion of patients with secondary PIRAMs in the corresponding groups was 99% and 98%, respectively (p=1.000). The most common secondary PI-RAMs in both groups were M36I (91%), H69K (34%) and L89M (30%). In conclusion, primary PI-RAMs are observed exclusively among PI-experienced patients, whereas secondary PI-RAMs are equally found in both PI-naive and PI-experienced patients. Further studies to define virologic response of HIV-1 subtype A/E to various PIs and clinical validation of PIRAMs in HIV-1 subtype A/E are essentially needed.

Keywords: HIV, protease inhibitor, resistance, mutations, subtype A/E, CRF 01_AE