Parkin Neil, Chappey Colombe, Maroldo Laura, Bates Michael, Hellmann Nicholas S, Petropoulos Christos J
Virologic, Inc., South San Francisco, California 94080, USA.
J Acquir Immune Defic Syndr. 2002 Oct 1;31(2):128-36. doi: 10.1097/00126334-200210010-00002.
To determine the extent to which genotype (GT) or phenotype (PT) methods provide HIV-1 drug resistance information that is overlapping or complementary, both tests were performed on 1378 patient plasma samples. Discordance, defined as determination of reduced susceptibility measured by PT but sensitivity by GT (PT-R/GT-S), or vice versa (PT-S/GT-R), was common: 83, 62, 43, and 28% of samples with evidence of drug resistance had at least 1, 2, 3, or 4 drugs discordant, respectively. Three types of discordance were observed: PT-R/GT-S, and PT-S/GT-R with or without the presence of mixtures at resistance-associated positions (25%, 34%, and 41% of all discordance, respectively). After accounting for mixtures, results for didanosine (30%), zalcitabine (18%), tenofovir (17%), abacavir (14%), lamivudine (12%), and amprenavir (11%) were discordant in >or= 10% of samples. PT-S/GT-R results were most common for didanosine and zalcitabine, whereas PT-R/GT-S results were most common for lamivudine and amprenavir. PT provided quantitative assessment of the degree of reduced susceptibility and identified reduced susceptibility (PT-R/GT-S) or normal susceptibility (PT-S/GT-R) that was not recognized by the GT interpretation algorithm. GT provided valuable information when mixtures were present and minor populations of drug resistant virus were not detected by phenotyping (PT-S/GT-R results). This demonstrates the complementary nature of information provided by PT and GT tests and suggests that their combined use can provide additional clinically-relevant information.
为了确定基因型(GT)或表型(PT)方法提供的HIV-1耐药性信息是重叠的还是互补的,对1378份患者血浆样本同时进行了这两种检测。不一致情况很常见,即PT检测显示敏感性降低但GT检测显示敏感性正常(PT-R/GT-S),或者反之(PT-S/GT-R):分别有83%、62%、43%和28%有耐药证据的样本至少有1、2、3或4种药物检测结果不一致。观察到三种类型的不一致情况:PT-R/GT-S,以及存在或不存在耐药相关位点混合情况的PT-S/GT-R(分别占所有不一致情况的25%、34%和41%)。在考虑混合情况后,去羟肌苷(30%)、扎西他滨(18%)、替诺福韦(17%)、阿巴卡韦(14%)、拉米夫定(12%)和安普那韦(11%)在≥10%的样本中检测结果不一致。PT-S/GT-R结果在去羟肌苷和扎西他滨检测中最为常见,而PT-R/GT-S结果在拉米夫定和安普那韦检测中最为常见。PT提供了对敏感性降低程度的定量评估,并识别出GT解释算法未识别的敏感性降低(PT-R/GT-S)或正常敏感性(PT-S/GT-R)。当存在混合情况且表型分析未检测到耐药病毒的少数群体时,GT提供了有价值的信息(PT-S/GT-R结果)。这证明了PT和GT检测所提供信息的互补性,并表明联合使用它们可以提供更多临床相关信息。