Limited clinical benefit of minority K103N and Y181C-variant detection in addition to routine genotypic resistance testing in antiretroviral therapy-naive patients
| Autor: | Karin J, Metzner, Alexandra U, Scherrer, Viktor, von Wyl, Jürg, Böni, Sabine, Yerly, Thomas, Klimkait, Vincent, Aubert, Hansjakob, Furrer, Hans H, Hirsch, Pietro L, Vernazza, Matthias, Cavassini, Alexandra, Calmy, Enos, Bernasconi, Rainer, Weber, Huldrych F, Günthard, S, Yerly |
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| Přispěvatelé: | University of Zurich, Metzner, K J |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Male
10028 Institute of Medical Virology Genotyping Techniques minority drug HIV Infections Drug resistance Anti-Retroviral Agents/therapeutic use Nucleoside Reverse Transcriptase Inhibitor 10234 Clinic for Infectious Diseases Immunology and Allergy resistant HIV ddc:616 virological failure Reverse-transcriptase inhibitor Genotyping Techniques/methods virus diseases Middle Aged HIV Reverse Transcriptase HIV-1/enzymology/genetics/isolation & purification Treatment Outcome Infectious Diseases Anti-Retroviral Agents 2723 Immunology and Allergy Female drug resistance testing Viral load medicine.drug Cohort study Adult medicine.medical_specialty Immunology antiretroviral therapy Mutation Missense 610 Medicine & health Microbial Sensitivity Tests Internal medicine Drug Resistance Viral medicine Humans Alleles Retrospective Studies 2403 Immunology business.industry Retrospective cohort study 2725 Infectious Diseases biochemical phenomena metabolism and nutrition Antiretroviral therapy Reverse transcriptase naive patients HIV-1 570 Life sciences biology HIV Infections/virology Microbial Sensitivity Tests/methods 1 variants business HIV Reverse Transcriptase/genetics |
| Zdroj: | Metzner, Karin J.; Scherrer, Alexandra U.; Von Wyl, Viktor; Böni, Jürg; Yerly, Sabine; Klimkait, Thomas; Aubert, Vincent; Furrer, Hansjakob; Hirsch, Hans H.; Vernazza, Pietro L.; Cavassini, Matthias; Calmy, Alexandra; Bernasconi, Enos; Weber, Rainer; Günthard, Huldrych F. (2014). Limited clinical benefit of minority K103N and Y181C-variant detection in addition to routine genotypic resistance testing in antiretroviral therapy-naive patients. AIDS, 28(15), pp. 2231-2239. Lippincott Williams & Wilkins 10.1097/QAD.0000000000000397 AIDS, Vol. 28, No 15 (2014) pp. 2231-9 |
| ISSN: | 0269-9370 |
| DOI: | 10.1097/QAD.0000000000000397 |
| Popis: | 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-naïve 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 sole 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. |
| Databáze: | OpenAIRE |
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