Details

Autor(en) / Beteiligte

• PEUCHANT, Olivia
• THIEBAUT, Rodolphe
• CAPDEPONT, Sophie
• LAVIGNOLLE-AURILLAC, Valérie
• NEAU, Didier
• MORLAT, Philippe
• DABIS, Francois
• FLEURY, Hervé
• MASQUELIER, Bernard

Titel

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

Ist Teil von

• AIDS (London), 2008-07, Vol.22 (12), p.1417-1423

Ort / Verlag

Hagerstown, MD: Lippincott Williams & Wilkins

Erscheinungsjahr

2008

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• 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. 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. 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. 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.