Buchacz Kate, Baker Rose, Ward Douglas J, Palella Frank J, Chmiel Joan S, Young Benjamin, Yangco Bienvenido G, Novak Richard M, Brooks John T
Divisions of HIV/AIDS Prevention, Centers for Disease Control and Prevention, 1600 Clifton Road, Mail Stop E45, Atlanta, GA 30333, USA.
AIDS Res Treat. 2012;2012:230290. doi: 10.1155/2012/230290. Epub 2012 Mar 14.
Background. Little is known about temporal trends in frequencies of clinically relevant ARV resistance mutations in HIV strains from U.S. patients undergoing genotypic testing (GT) in routine HIV care. Methods. We analyzed cumulative frequency of HIV resistance among patients in the HIV Outpatient Study (HOPS) who, during 1999-2008 and while prescribed antiretrovirals, underwent GT with plasma HIV RNA >1,000 copies/mL. Exposure ≥4 months to each of three major antiretroviral classes (NRTI, NNRTI and PI) was defined as triple-class exposure (TCE). Results. 906 patients contributed 1,570 GT results. The annual frequency of any major resistance mutations decreased during 1999-2008 (88% to 79%, P = 0.05). Resistance to PIs decreased among PI-exposed patients (71% to 46%, P = 0.010) as exposure to ritonavir-boosted PIs increased (6% to 81%, P < 0.001). Non-significant declines were observed in resistance to NRTIs among NRTI-exposed (82% to 67%), and triple-class-resistance among TCE patients (66% to 41%), but not to NNRTIs among NNRTI-exposed. Conclusions. HIV resistance was common but declined in HIV isolates from subgroups of ARV-experienced HOPS patients during 1999-2008. Resistance to PIs among PI-exposed patients decreased, possibly due to increased representation of patients whose only PI exposures were to boosted PIs.
背景。对于在美国接受常规HIV治疗的患者进行基因分型检测(GT)时,HIV毒株中临床相关抗逆转录病毒(ARV)耐药突变频率的时间趋势,人们了解甚少。方法。我们分析了HIV门诊研究(HOPS)中患者的HIV耐药累积频率,这些患者在1999年至2008年期间接受抗逆转录病毒治疗,且血浆HIV RNA>1000拷贝/mL时接受了GT检测。暴露于三种主要抗逆转录病毒药物类别(核苷类逆转录酶抑制剂、非核苷类逆转录酶抑制剂和蛋白酶抑制剂)中每种药物至少4个月被定义为三类暴露(TCE)。结果。906名患者提供了1570次GT检测结果。1999年至2008年期间,任何主要耐药突变的年频率有所下降(从88%降至79%,P = 0.05)。随着对利托那韦增强型蛋白酶抑制剂的暴露增加(从6%增至81%,P < 0.001),暴露于蛋白酶抑制剂的患者中对蛋白酶抑制剂的耐药性下降(从71%降至46%,P = 0.010)。在暴露于核苷类逆转录酶抑制剂的患者中,对核苷类逆转录酶抑制剂的耐药性有非显著下降(从82%降至67%),在TCE患者中三类耐药性有非显著下降(从66%降至41%),但在暴露于非核苷类逆转录酶抑制剂的患者中对非核苷类逆转录酶抑制剂的耐药性没有下降。结论。HIV耐药现象常见,但在1999年至2008年期间,来自有ARV治疗经验的HOPS患者亚组的HIV分离株中耐药性有所下降。暴露于蛋白酶抑制剂的患者中对蛋白酶抑制剂的耐药性下降,可能是由于仅暴露于增强型蛋白酶抑制剂的患者比例增加。