Palmer Sarah, Boltz Valerie F, Chow Jeremy Y, Martinson Neil A, McIntyre James A, Gray Glenda E, Hopley Mark J, Mayers Douglas, Robinson Patrick, Hall David B, Maldarelli Frank, Coffin John M, Mellors John W
HIV Drug Resistance Program, NCI, NIH, Frederick, MD, USA.
Antivir Ther. 2012;17(2):327-36. doi: 10.3851/IMP1946. Epub 2011 Nov 3.
In the Treatment Options Preservation Study (TOPS) trial, 4 or 7 days of Combivir (CBV; zidovudine/lamivudine) with maternal single-dose nevirapine (sdNVP) significantly reduced the emergence of NVP resistance as determined by virus population genotyping. To detect NVP resistance with greater sensitivity, we analysed TOPS samples by allele-specific real-time PCR (ASP).
In a random subset of women from each arm of the trial, plasma samples from before and 6 weeks after sdNVP were analysed using ASP at codons 103, 181, 184 and 190.
Samples were analysed from 27 women in the sdNVP arm and 24 each in the CBV 4-day (sdNVP/CBV4) and 7-day (sdNVP/CBV7) arms. ASP detected NVP-resistant variants in week 6 samples from 70% of women in the sdNVP arm, 29% in the sdNVP/CBV4 arm and 33% in sdNVP/CBV7 arm (P<0.01 for sdNVP/CBV4 or sdNVP/CBV7 versus sdNVP; P=1.0 for sdNVP/CBV4 versus sdNVP/CBV7). Lamivudine resistance was detected by ASP in only 1 of 51 women who received CBV.
Short-course CBV significantly reduced but did not eliminate the emergence of NVP resistance after sdNVP. NVP-resistant variants were detected in about one-third of women despite CBV treatment, but the duration of persistence and clinical impact of these variants in response to antiretroviral therapy is uncertain.
在治疗方案保留研究（TOPS）试验中，根据病毒群体基因分型结果，使用4天或7天的双汰芝（CBV；齐多夫定/拉米夫定）联合产妇单剂量奈韦拉平（sdNVP）可显著降低奈韦拉平耐药性的出现。为了更灵敏地检测奈韦拉平耐药性，我们采用等位基因特异性实时PCR（ASP）分析了TOPS试验的样本。
在该试验各治疗组的随机抽取的女性子集中，对sdNVP给药前及给药后6周的血浆样本进行了第103、181、184和190密码子的ASP分析。
分析了sdNVP组27名女性以及CBV 4天组（sdNVP/CBV4）和7天组（sdNVP/CBV7）各24名女性的样本。ASP在sdNVP组70%的女性、sdNVP/CBV4组29%的女性和sdNVP/CBV7组33%的女性的第6周样本中检测到了奈韦拉平耐药变异体（sdNVP/CBV4或sdNVP/CBV7组与sdNVP组相比，P<0.01；sdNVP/CBV4组与sdNVP/CBV7组相比，P=1.0）。在接受CBV治疗的51名女性中，只有1名通过ASP检测到拉米夫定耐药。
短期使用CBV可显著降低但不能消除sdNVP后奈韦拉平耐药性的出现。尽管接受了CBV治疗，仍在约三分之一的女性中检测到了奈韦拉平耐药变异体，但这些变异体对抗逆转录病毒治疗反应的持续时间和临床影响尚不确定。
