Drug-Class-Wide Resistance to Antiretrovirals in HIV-Infected Patients Failing Therapy: Prevalence, Risk Factors and Virological Outcome
Drug-Class-Wide Resistance to Antiretrovirals in HIV-Infected Patients Failing Therapy: Prevalence, Risk Factors and Virological Outcome
复制标题
治疗失败的艾滋病毒感染者对抗逆转录病毒药物的全药物耐药性：患病率、危险因素和病毒学结果
作者：
V. Tozzi;M. Zaccarelli;S. Bonfigli;P. Lorenzini;G. Liuzzi;M. Trotta;F. Forbici;C. Gori;A. Bertoli;R. Bellagamba;P. Narciso;C. Perno;A. Antinori
背景 抗逆转录病毒药物的全药物耐药性 (DCWR) 大大减少了治疗选择。方法 对 602 名接受基因型耐药测试 (GRT) 的高效抗逆转录病毒治疗 (HAART) 失败患者的数据库进行了分析。 DCWR是根据国际艾滋病协会共识定义的。建立了多重逻辑回归模型来定义与 DCWR 显着相关的因素并评估对挽救方案的病毒学反应。结果 592 名 NRTI 暴露患者中，28.5% 观察到 NRTI DCWR；284 名 NNRTI 暴露患者中，57.7% 观察到 NNRTI DCWR；412 名 PI 暴露患者中，19.9% 观察到 PI DCWR；112 名三级暴露患者中，21.4% 观察到三级耐药。 NRTI 和 PI DCWR 的患病率随接触同一类别的年份显着增加，分别从 8.9%（<1 年）至 35.3%（>4 年）和 1.2%（<1 年）至 34.8%（>4 年）（趋势 P<0.001）。治疗每年，发生 NRTI 和 PI DCWR 的风险增加 25%（95% 置信区间 [CI]：1.6%–51.3%）和 53%（20.5%–94.3%），之前每次失败的 NRTI 和 PI DCWR 风险增加 17%（95% CI：5.6%–29.3%）和 32%（17.7%–50.3%）。分别含有 PI 的方案。由于至少四种核苷类似物突变 (NAM) 导致的 NRTI DCWR 随着 NRTI 暴露年份的增加而增加，从 8.9%（<1 年）增加到 32.6%（>4 年；P<0.001，趋势）。调整混杂因素后，NRTI（OR：0.750；95% CI：0.574-0.979）、NNRTI（OR：0.746；95% CI：0.572-0.975）、PI（OR：0.655；95% CI：0.655；95% CI： 0.456–0.941），三级（OR：0.220；95% CI：0.082–0.593）电阻。结论 发生 NRTI 和 PI DCWR 的可能性随着课堂暴露时间的长短和先前失败的治疗方案的数量而增加。相比之下，在 NNRTI 失败的患者中，1 年内观察到高水平的 NNRTI DCWR，并且随着时间的推移，患病率稳定。随着 NRTI DCWR 时间的推移，患病率增加是由于 NAM 的积累。 DCWR 对 NRTI、NNRTI、PI 或所有三者的组合与后续 HAART 治疗方案病毒学失败的可能性增加相关。
Background Drug-class-wide resistance (DCWR) to anti-retrovirals substantially reduces treatment options. Methods A database of 602 patients failing highly active antiretroviral therapy (HAART) undergoing genotypic resistance test (GRT) was analysed. DCWR was defined according to the International AIDS Society consensus. A multiple logistic regression model was built to define factors significantly associated with DCWR and to assess virological response to salvage regimens. Results NRTI DCWR was observed in 28.5% of 592 NRTI-exposed patients, NNRTI DCWR in 57.7% of 284 NNRTI exposed patients, PI DCWR in 19.9% of 412 PI exposed patients, and three-class resistance in 21.4% of 112 three-class-exposed patients. The prevalence of NRTI and PI DCWR increased significantly by year of exposure to the same class from 8.9% (<1 year) to 35.3% (>4 years) and from 1.2% (<1 year) to 34.8% (>4 years), respectively (P<0.001, for trend). The risk of developing NRTI and PI DCWR increased by 25% (95% confidence interval [CI]: 1.6%–51.3%) and by 53% (20.5%–94.3%) for each year of treatment, and by 17% (95% CI: 5.6%–29.3%) and by 32% (17.7%–50.3%) for each previous failing NRTI- and PI-containing regimen, respectively. NRTI DCWR due to at least four nucleoside analogues mutations (NAMs) increased by year of NRTI exposure from 8.9% (<1 year) to 32.6% (>4 years; P<0.001, for trend). After adjustment for confounding factors, the probability of achieving plasma viral load <500 copies/ml was significantly reduced in patients with NRTI (OR: 0.750; 95% CI: 0.574–0.979), NNRTI (OR: 0.746; 95% CI: 0.572–0.975), PI (OR: 0.655; 95% CI: 0.456–0.941), three-class (OR: 0.220; 95% CI: 0.082–0.593) resistance. Conclusions The probability of developing NRTI and PI DCWR increased with length of class exposure and with the number of previously failing regimens. By contrast, high levels of NNRTI DCWR were observed within 1 year in NNRTI-failing patients, with a steady prevalence over time. The increase in prevalence with time of NRTI DCWR was due to the accumulation of NAMs. DCWR to NRTIs, NNRTIs, PIs or all the three together was associated with an increased probability of virological failure to subsequent HAART regimens.
临床实践中的人类免疫缺陷病毒 1 蛋白酶抑制剂：病毒学结果的预测因子。
影响因子：
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作者：
Valdez,H;Lederman,MM;Woolley,I;Walker,CJ;Vernon,LT;Hise,A;Gripshover,BM
通讯作者：
Gripshover,BM