Trends of transmitted drug resistance of HIV-1 and its impact on treatment response to first-line antiretroviral therapy in Taiwan

Abstract

To determine the impact of transmitted drug resistance (TDR) of HIV-1 on treatment outcome in areas where routine testing for drug resistance mutations may not be available before combination antiretroviral therapy (cART) is initiated. Genotypic resistance assays were performed on HIV isolates from archived blood samples obtained from 1349 antiretroviral-naive HIV-1-infected patients in Taiwan from 2000 to 2010. Resistance mutations were interpreted with the use of the HIVdb program of the Stanford University HIV Drug Resistance Database. The genotypic sensitivity score (GSS) of the regimens prescribed was calculated. A matched case-control study was conducted to assess the impact of TDR on treatment outcomes. The overall prevalence of TDR to any antiretroviral agent was 8.0%, declining from 12.3% in 2003-06 to 5.1% in 2007-10. In the matched case-control study, 31 patients with high- or intermediate-level resistance, 16 with low-level resistance and 89 controls were enrolled. Compared with regimens with GSS >2.5, initiation of regimens with GSS ≤2.5 was associated with a higher treatment failure rate (39.3% versus 15.7%, P = 0.02) and shorter time to treatment failure (log-rank P < 0.001). In patients receiving regimens with GSS ≤2.5, protease inhibitor-based regimens were less likely to result in treatment failure, compared with non-nucleoside reverse-transcriptase inhibitor-based regimens (hazard ratio 0.26, 95% CI 0.06-1.12, P = 0.07). In Taiwan the prevalence of TDR of HIV-1 strains declined and stabilized between 2007 and 2010. Receipt of antiretroviral regimens with GSS ≤2.5 was associated with poorer treatment responses than regimens with GSS >2.5.