title: Comparison of protease inhibitor (PI) resistance-associated mutations between PI-naïve and PI-experienced HIV-1 infected patients in Thailand where subtype A/E is predominant.
abstract: Protease inhibitor (PI) resistance-associated mutations (RAMs) are commonly observed in PI-naïve patients who 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-naïve 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-naïve 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-naïve group (31.5 vs. 46.8 months, p=0.028). Proportion of patients with primary PI-RAMs was 2.7% in PI-naïve 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 PI-RAMs 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-naïve and PI-experienced patients. Further studies to define virologic response of HIV-1 subtype A/E to various PIs and clinical validation of PI-RAMs in HIV-1 subtype A/E are essentially needed.
authors.affiliation: Department of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Surasak
authors.initials: S
authors.lastname: Wiboonchutikul
authors.forename: Somnuek
authors.initials: S
authors.lastname: Sungkanuparph
authors.forename: Chonlaphat
authors.initials: C
authors.lastname: Sukasem
authors.forename: Chorthip
authors.initials: C
authors.lastname: Wathipthun
authors.forename: Wasun
authors.initials: W
authors.lastname: Chantratita
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D016333:HIV Protease / Q000235:genetics*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000187:drug effects; D012189:Retrospective Studies; D013785:Thailand
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D016333:HIV Protease