Treatment outcomes and HIV drug resistance of patients switching to second-line regimens after long-term first-line antiretroviral therapy: An observational cohort study

长期接受一线抗逆转录病毒治疗后转为二线治疗方案的患者的治疗结果和HIV耐药性:一项观察性队列研究

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Abstract

To investigate the responses to switching to second-line regimens among patients who had received a long-term first-line antiretroviral therapy.Patients switching to second-line regimens from June 2008 to June 2015 were enrolled from an observational cohort. In addition, patients continuing first-line therapy and had a viral load <1000 copies/mL were included as controls in July 2012. All these patients were followed-up for 36 months or until June 2016. The virological, immunological outcomes, and drug resistance were evaluated. Virological failure was defined as viral load ≥1000 copies/mL after 6 months of treatment since the start of the study.There were 304 patients switching to second-line regimens and 46 patients remaining on first-line therapy enrolled while having received first-line therapy for a median of 7.6 years. Patients with plasma viral load (VL) ≥1000 copies/mL before switching to second-line regimens had a sharp decline in the proportion of virological failure with 26.7%, 20.4%, and 17.0% at 12, 24, and 36 months after regimen switch, respectively (trend test, P < .001). Among these patients, individuals with drug resistance (DR) had a better virological responses as compared with those without DR after regimen switching. While patients with VL <1000 copies/mL at inclusion remained a high rate of viral suppression after switching to second-line regimens. So did patients continuing first-line therapy. Among patients with VL ≥1000 copies/mL before switching to second-line regimens, the rates of drug resistance were decreased from 79.4% at inclusion to 7.5% at 36 months of regimen switch, with the proportion of NRTI- and NNRTI-related drug resistance from 67.2% and 79.4% to 5.4% and 7.5%, respectively. No PI-related resistance was found. Having self-reported missing doses within a month at follow-ups were independently associated with virological failure at 36 months of switching.HIV-infected patients had viral load ≥1000 copies/mL at regimen switch after a long duration of first-line therapy had good virological responses to second-line regimens, especially those harbored drug resistant variants at regimen switch. However, patients with suppressive first-line therapy did not appear to benefit virologically from switching to second-line regimens.

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