Transmission of HIV-1 minority-resistant variants and response to first-line antiretroviral therapy.: Transmission of minority resistant HIV-1Reportar como inadecuado




Transmission of HIV-1 minority-resistant variants and response to first-line antiretroviral therapy.: Transmission of minority resistant HIV-1 - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

* Corresponding author 1 Variabilité génomique des virus 2 Biostatistique 3 Service des maladies infectieuses

Abstract : BACKGROUND: The transmission of drug-resistant HIV-1 can impair the virological response to antiretroviral therapy. Minority-resistant variants have been detected in acute seroconverters. We investigated the clinical relevance of the detection of majority and minority-resistant variants in an observational study in antiretroviral therapy naive, recently infected patients. METHODS: We included patients infected between 1996 and 2005, with a plasma sample obtained less than 18 months after seroconversion and prior to antiretroviral therapy initiation. Majority-resistant variants were determined by direct population sequencing. Minority-resistant variants were searched by allele-specific PCR for the mutations K103N and M184V in reverse transcriptase and L90M in protease. The association between resistance and viroimmunological response to antiretroviral therapy was estimated by using a piecewise linear mixed model. RESULTS: Majority-resistant variants were detected in 23-172 13.4% patients. Patients with majority-resistant variants had a lower mean plasma viral load and higher mean CD4 cell count at baseline compared with those without resistance. The decrease in viral load between 1 and 6 months on antiretroviral therapy was significantly steeper in patients with sensitive viruses compared with those with majority-resistant variants P = 0.029. Minority-resistant variants were detected in 21-73 29% patients with wild-type viruses at sequencing analysis. The presence of minority-resistant variants did not modify baseline viral load and CD4 cell count and did not affect the changes in viral load and CD4 cell count. CONCLUSION: The transmission of majority-resistant variants, but not minority-resistant variants, influenced the response to antiretroviral therapy in this prospective study. The detection of the transmission of minority-resistant variants warrants further clinical validation.

Keywords : HIV-1 drug resistance transmission antiretroviral therapy minority variants





Autor: Olivia Peuchant - Rodolphe Thiébaut - Sophie Capdepont - Valerie Lavignolle-Aurillac - Didier Neau - Philippe Morlat - François

Fuente: https://hal.archives-ouvertes.fr/



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