Audelin Anne Margrethe, Lohse Nicolai, Obel Niels, Gerstoft Jan, Jørgensen Louise Bruun
Department of Virology, Statens Serum Institut, Copenhagen, Denmark.
Antivir Ther. 2009;14(7):995-1000. doi: 10.3851/IMP1412.
Newer antiretroviral treatment regimens for HIV carry a lower risk of inducing drug resistance mutations. We estimated changes in incidence rates (IRs) of new mutations in HIV-infected individuals receiving highly active antiretroviral therapy (HAART).
Population-based data were obtained from the Danish HIV Cohort Study and the Danish HIV Sequence Database. We included treatment-naive patients initiating HAART after December 1997 and computed time to first drug resistance mutation, identified as new mutations detected within 1 year after a 60-day period of treatment failure (HIV RNA>1,000 copies/ml). We estimated annual IRs of new resistance mutations towards nucleoside reverse transcriptase inhibitors (NRTIs), non-NRTIs (NNRTIs) and protease inhibitors (PI), and of new specific resistance mutations.
A total of 1,829 individuals were observed for 7,294 person-years at risk (PYR). The IR of NRTI resistance decreased from 13.1 per 1,000 PYR (95% confidence interval [CI] 4.9-35.0) in 1999 to 3.7 (1.9-7.2) in 2004-2005 (test for trend P=0.024). The IR of NNRTI resistance decreased from 15.4 (2.2-109.6) in 1999 to 7.9 (4.6-13.6) in 2004-2005 (P=0.077). The IR of PI resistance decreased from 7.5 (1.4-21.8) in 1999 to 2.9 (0.7-11.4) in 2002-2003 (P=0.148). The IRs were low for specific resistance mutations, except for M184V (IR 5.6 [4.0-7.9]) and K103N (IR 8.2 [5.6-12.0]).
The incidence of acquired drug resistance has decreased among HIV-infected patients treated with HAART in Denmark during 1999-2005.
新型抗逆转录病毒治疗方案降低了诱导HIV耐药性突变的风险。我们估计了接受高效抗逆转录病毒治疗（HAART）的HIV感染者中新突变发生率（IR）的变化。
基于人群的数据来自丹麦HIV队列研究和丹麦HIV序列数据库。我们纳入了1997年12月后开始接受HAART的初治患者，并计算首次出现耐药性突变的时间，将其定义为在治疗失败（HIV RNA>1000拷贝/ml）60天后1年内检测到的新突变。我们估计了对核苷类逆转录酶抑制剂（NRTIs）、非核苷类逆转录酶抑制剂（NNRTIs）和蛋白酶抑制剂（PI）的新耐药性突变以及新的特定耐药性突变的年发生率。
共观察到1829人，总计7294人年的风险期（PYR）。NRTI耐药的发生率从1999年的每1000 PYR 13.1（95%置信区间[CI]4.9 - 35.0）降至2004 - 2005年的3.7（1.9 - 7.2）（趋势检验P = 0.024）。NNRTI耐药的发生率从1999年的15.4（2.2 - 109.6）降至2004 - 2005年的7.9（4.6 - 13.6）（P = 0.077）。PI耐药的发生率从1999年的7.5（1.4 - 21.8）降至2002 - 2003年的2.9（0.7 - 11.4）（P = 0.148）。除M184V（发生率5.6[4.0 - 7.9]）和K103N（发生率8.2[5.6 - 12.0]）外，特定耐药性突变的发生率较低。
1999 - 2005年期间，丹麦接受HAART治疗的HIV感染者中获得性耐药的发生率有所下降。
