Zheng Yu, Hughes Michael D, Lockman Shahin, Benson Constance A, Hosseinipour Mina C, Campbell Thomas B, Gulick Roy M, Daar Eric S, Sax Paul E, Riddler Sharon A, Haubrich Richard, Salata Robert A, Currier Judith S
Harvard School of Public Health.
Harvard School of Public Health Harvard Medical School, Boston, Massachusetts.
Clin Infect Dis. 2014 Sep 15;59(6):888-96. doi: 10.1093/cid/ciu367. Epub 2014 May 19.
Virologic failure (VF) on a first-line ritonavir-boosted protease inhibitor (PI/r) regimen is associated with low rates of resistance, but optimal management after failure is unknown.
The analysis included participants in randomized trials who experienced VF on a first-line regimen of PI/r plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) and had at least 24 weeks of follow-up after VF. Antiretroviral management and virologic suppression (human immunodeficiency virus type 1 [HIV-1] RNA <400 copies/mL) after VF were assessed.
Of 209 participants, only 1 participant had major PI-associated treatment-emergent mutations at first-line VF. The most common treatment approach after VF (66%) was to continue the same regimen. The virologic suppression rate 24 weeks after VF was 64% for these participants, compared with 72% for those who changed regimens (P = .19). Participants remaining on the same regimen had lower NRTI resistance rates (11% vs 30%; P = .003) and higher CD4(+) cell counts (median, 275 vs 213 cells/µL; P = .005) at VF than those who changed. Among participants remaining on their first-line regimen, factors at or before VF significantly associated with subsequent virologic suppression were achieving HIV-1 RNA <400 copies/mL before VF (odds ratio [OR], 3.39 [95% confidence interval {CI}, 1.32-8.73]) and lower HIV-1 RNA at VF (OR for <10 000 vs ≥10 000 copies/mL, 3.35 [95% CI, 1.40-8.01]). Better adherence after VF was also associated with subsequent suppression (OR for <100% vs 100%, 0.38 [95% CI, .15-.97]). For participants who changed regimens, achieving HIV-1 RNA <400 copies/mL before VF also predicted subsequent suppression.
For participants failing first-line PI/r with no or limited drug resistance, remaining on the same regimen is a reasonable approach. Improving adherence is important to subsequent treatment success.
一线利托那韦增强型蛋白酶抑制剂（PI/r）方案出现病毒学失败（VF）时耐药率较低，但失败后的最佳管理方案尚不清楚。
分析纳入了在PI/r加2种核苷类逆转录酶抑制剂（NRTIs）一线方案中出现VF且VF后至少随访24周的随机试验参与者。评估VF后的抗逆转录病毒治疗管理和病毒学抑制情况（1型人类免疫缺陷病毒[HIV-1]RNA<400拷贝/mL）。
在209名参与者中，只有1名参与者在一线VF时出现主要的PI相关治疗中出现的突变。VF后最常见的治疗方法（66%）是继续使用相同方案。这些参与者VF后24周的病毒学抑制率为64%，而更换方案者为72%（P = 0.19）。继续使用相同方案的参与者在VF时的NRTI耐药率较低（11%对30%；P = 0.003），CD4(+)细胞计数较高（中位数，275对213个细胞/µL；P = 0.005）。在继续使用一线方案的参与者中，VF时或VF前与随后病毒学抑制显著相关的因素是在VF前实现HIV-1 RNA<400拷贝/mL（优势比[OR]，3.39[95%置信区间{CI}，1.32 - 8.73]）和VF时较低的HIV-1 RNA（<10000对≥10000拷贝/mL的OR，3.35[95%CI，1.40 - 8.01]）。VF后更好的依从性也与随后的抑制相关（<100%对100%的OR，0.38[95%CI，0.15 - 0.97]）。对于更换方案的参与者，在VF前实现HIV-1 RNA<400拷贝/mL也可预测随后的抑制情况。
对于一线PI/r治疗失败且耐药无或有限的参与者，继续使用相同方案是一种合理的方法。提高依从性对后续治疗成功很重要。
