关键词: HIV-1, 高效抗逆转录病毒治疗(HAART), 基因型耐药, 突变

Abstract: Objective To analyze drug resistance status in 20 HIV/AIDS patients who had received highly active antiretroviral therapy(HAART) with treatment failure and to evaluate the significance of drug resistance test. Methods Plasma viral load, CD4⁺ T lymphocyte counts were determined by Versant HIV-1 RNA 3.0 and TriTEST CD4 FITC/CD8 PE/CD3 PerCP Reagent, respectively. Using the Trugene HIV-1 Genotyping kit and OpenGene DNA Sequencing System, we sequenced HIV-1 target genes and analyzed drug-related mutations. We used molecular biology software(such as Blast) to identify HIV-1 subtypes. Results Of the 20 patients, 17 had pre-treatment plasma samples, and 1 case showed an non-nucleoside reverse transcriptase inhibitors(NNRTIs)-related resistance mutation before HAART. When antiviral treatment initiated, 3/20 cases with no drug resistanceǒrelated mutations were found at any time point; in 17/20 cases drug resistanceǒrelated mutation was detected. Thirteen of 17 patients showed NNRTI-related mutations, mostly in K103N, Y188L, Y181C, V106M and G190A. Eleven of 17 patients showed Nucleoside/Nucleotide Reverse Transcriptase Inhibitors(NRTIs)-related mutations, mostly in M184V, T/215Y/F, D67N, K70R and K219E/Q. Three of 17 patients were showed Protease Inhibitors(PIs)-related mutations, with primary mutation site at M46I/L and V82F/A. In secondary mutation of PI, M36I and L63P were the most common sites. Of the 20 patients, had type B infection, had 5(25%, 5/20) CRF01_AE recombinants another, had 5(25%, 5/20) CRF07_BC recombinants, had CRF06_CPX1 recombinants is 1(5%, 1/20). Conclusion For patients with treatment failure and drug-resistance, mutation detection can help clinicians determine the cause of treatment failure and optimize the medication combinations. Termination or change of treatment programs could significantly affect drug resistance test results, and therefore, clinicians should be fully aware of the treatment situation of patients before drug resistance test. The subtypes revealed that the HIV subtypes have an association with routes of infection.

Key words: human immunodeficiency virus(HIV-1), highly active antiretroviral therapy(HAART), genotyping resistance, mutation