Transmission of HIV-1 minority-resistant variants and response to first-line antiretroviral therapy

Autor: Peuchant, Olivia, Thiébaut, Rodolphe, Capdepont, Sophie, Lavignolle-Aurillac, Valerie, Neau, Didier, Morlat, Philippe, Dabis, François, Fleury, Hervé, Masquelier, Bernard
Přispěvatelé: Variabilité génomique des virus, Université Bordeaux Segalen - Bordeaux 2-IFR66, Biostatistique, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des maladies infectieuses, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin
Jazyk: angličtina
Rok vydání: 2008
Předmět:
Zdroj: AIDS
AIDS, Lippincott, Williams & Wilkins, 2008, 22 (12), pp.1417-23. ⟨10.1097/QAD.0b013e3283034953⟩
ISSN: 0269-9370
DOI: 10.1097/QAD.0b013e3283034953⟩
Popis: International audience; 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.
Databáze: OpenAIRE
Externí odkaz: