Prevalence of genotypic resistance to nucleoside analogues and protease inhibitors in Spain

Objective: To examine the prevalence of resistance mutations to nucleoside reverse transcriptase inhibitors (NRTI) and protease inhibitors (PI) in a r epresentative HIV-1 population in Spain. Methods: A cross-sectional study was conducted including 601 HIV-infected p atients who attended 20 Spanish hospitals in June 1998. Drug resistant muta tions were examined using hybridization line probe assays (LiPA). The 6 bp insert at position 69 and the codon 75 mutant were examined by sequencing a nalysis in specimens lacking reactivity to 69/70 and 74 bands an LiPA, resp ectively. Results: Primary resistance to NRTI was recognized in nine out of 52 (17%) naive individuals, whereas primary resistance to PI was found in seven out of 126 (6%) PI-naive patients. The codons most frequently involved in NRTI resistance were at positions 70 (66%), 184 (44%), 215 (33%), and 41 (11%), whereas the most common PI resistance mutation was at codon 82 (6/7 subject s). In pre-treated patients, the overall prevalence of resistant genotypes was 72.9% for NRTI and 27.2% for PI. The most frequent NRTI mutations occur red at codons 184 (38.5%), 215 (30.1%), and 41 (22.5%), whereas the most fr equent PI mutations in pre-treated subjects were found at positions 82 (15. 8%) and 84 (11.4%). Overall, patients who began triple combinations as init ial therapy showed a lower number of key resistance mutations than those wh o began highly active antiretroviral therapy (HAART) after being exposed to NRTI for a period of time (mean number of mutations, 0.1 versus 1.8, P < 0 .05). Codon 75 mutant was found in three out of 387 patients (0.7%), wherea s no insertions at codon 69 were recognized. Conclusion: The prevalence of primary genotypic resistance to NRTI and PI i n Spain was 17% and 6%, respectively. Zidovudine, lamivudine, indinavir and ritonavir were the drugs most frequently affected. These data support the use of resistance testing prior to the introduction of first-line antiretro viral therapies in Spain. Among pretreated subjects, drug resistance genoty pes were less prevalent in those who began HAART as initial therapy. (C) 20 00 Lippincott Williams & Wilkins.