Limited clinical benefit of minority K103N and Y181C-variant detection in addition to routine genotypic resistance testing in antiretroviral therapy-naive patients

作者：Metzner Karin J^*; Scherrer Alexandra U; von Wyl Viktor; Boeni Juerg; Yerly Sabine; Klimkait Thomas; Aubert Vincent; Furrer Hansjakob; Hirsch Hans H; Vernazza Pietro L; Cavassini Matthias; Calmy Alexandra; Bernasconi Enos; Weber Rainer; Guenthard Huldrych F

来源：AIDS, 2014, 28(15): 2231-2239.

DOI：10.1097/QAD.0000000000000397

• antiretroviral therapy
• antiretroviral therapy-naive patients
• drug resistance testing
• minority drug-resistant HIV-1 variants
• virological failure

Objective:The presence of minority nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant HIV-1 variants prior to antiretroviral therapy (ART) has been linked to virologic failure in treatment-naive patients.Design:We performed a large retrospective study to determine the number of treatment failures that could have been prevented by implementing minority drug-resistant HIV-1 variant analyses in ART-naive patients in whom no NNRTI resistance mutations were detected by routine resistance testing.Methods:Of 1608 patients in the Swiss HIV Cohort Study, who have initiated first-line ART with two nucleoside reverse transcriptase inhibitors (NRTIs) and one NNRTI before July 2008, 519 patients were eligible by means of HIV-1 subtype, viral load and sample availability. Key NNRTI drug resistance mutations K103N and Y181C were measured by allele-specific PCR in 208 of 519 randomly chosen patients.Results:Minority K103N and Y181C drug resistance mutations were detected in five out of 190 (2.6%) and 10 out of 201 (5%) patients, respectively. Focusing on 183 patients for whom virologic success or failure could be examined, virologic failure occurred in seven out of 183 (3.8%) patients; minority K103N and/or Y181C variants were present prior to ART initiation in only two of those patients. The NNRTI-containing, first-line ART was effective in 10 patients with preexisting minority NNRTI-resistant HIV-1 variant.Conclusion:As revealed in settings of case-control studies, minority NNRTI-resistant HIV-1 variants can have an impact on ART. However, the implementation of minority NNRTI-resistant HIV-1 variant analysis in addition to genotypic resistance testing (GRT) cannot be recommended in routine clinical settings. Additional associated risk factors need to be discovered.

• 出版日期2014-9
• 单位河北医科大学