Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
J Infect Dis. 2013 Mar 15;207(6):893-7. doi: 10.1093/infdis/jis925. Epub 2012 Dec 21.
Drug-resistant human immunodeficiency virus type 1 (HIV-1) minority variants increase the risk of virologic failure for first-line nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens. We performed a pooled analysis to evaluate the relationship between NNRTI-resistant minority variants and the likelihood and types of resistance mutations detected at virologic failure. In multivariable logistic regression analysis, higher NNRTI minority variant copy numbers, non-white race, and nevirapine use were associated with a higher risk of NNRTI resistance at virologic failure. Among participants on efavirenz, K103N was the most frequently observed resistance mutation at virologic failure regardless of the baseline minority variant. However, the presence of baseline Y181C minority variant was associated with a higher probability of Y181C detection after virologic failure. NNRTI regimen choice and preexisting NNRTI-resistant minority variants were both associated with the probability and type of resistance mutations detected after virologic failure.
耐药性人类免疫缺陷病毒 1 型（HIV-1）少数变异体增加了一线非核苷类逆转录酶抑制剂（NNRTI）为基础的治疗方案发生病毒学失败的风险。我们进行了一项汇总分析，以评估 NNRTI 耐药性少数变异体与病毒学失败时检测到的耐药突变的可能性和类型之间的关系。在多变量逻辑回归分析中，较高的 NNRTI 少数变异体拷贝数、非白种人种族和奈韦拉平的使用与病毒学失败时发生 NNRTI 耐药的风险增加相关。在接受依非韦伦治疗的参与者中，无论基线少数变异体如何，K103N 都是病毒学失败时最常观察到的耐药突变。然而，基线 Y181C 少数变异体的存在与病毒学失败后 Y181C 检测的可能性更高相关。NNRTI 方案选择和预先存在的 NNRTI 耐药性少数变异体都与病毒学失败后检测到的耐药突变的可能性和类型相关。
