Transmission of HIV-1 minority-resistant variants and response to first-line antiretroviral therapy
| Autor: | Olivia, Peuchant, Rodolphe, Thiébaut, Sophie, Capdepont, Valérie, Lavignolle-Aurillac, Didier, Neau, Philippe, Morlat, François, Dabis, Hervé, Fleury, Bernard, Masquelier, D, Touchard |
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| 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: |
Male
Genotype Anti-HIV Agents Immunology Population antiretroviral therapy HIV Infections Polymerase Chain Reaction 03 medical and health sciences 0302 clinical medicine HIV Protease Drug Resistance Viral Humans Immunology and Allergy Medicine 030212 general & internal medicine Seroconversion Sida education Retrospective Studies 0303 health sciences education.field_of_study biology 030306 microbiology business.industry minority variants transmission Viral Load Resistance mutation biology.organism_classification Virology HIV Reverse Transcriptase Reverse transcriptase CD4 Lymphocyte Count 3. Good health Infectious Diseases Mutation Lentivirus HIV-1 RNA Viral Female [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie Viral disease business Viral load HIV-1 drug resistance |
| 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 |
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