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

Peuchant, Oliviaa; Thiébaut, Rodolpheb; Capdepont, Sophiea; Lavignolle-Aurillac, Valérieb; Neau, Didierb,c; Morlat, Philippec; Dabis, Françoisb; Fleury, Hervéa; Masquelier, Bernarda; and the ANRS CO3 Aquitaine Cohort

doi: 10.1097/QAD.0b013e3283034953
Basic Science

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.

From the aBordeaux University Hospital, Virology Laboratory, and Victor Segalen Bordeaux 2 University, France

bINSERM U897, ISPED, Victor Segalen Bordeaux 2 University, France

cBordeaux University Hospital, Infectious Diseases Department, Bordeaux, France.

*Participants listed in appendix.

Received 22 October, 2007

Revised 6 March, 2008

Accepted 2 April, 2008

Correspondence to Dr Bernard Masquelier, Laboratoire de Virologie CHU de Bordeaux, Hôpital Pellegrin, Place Amélie Raba Léon, 33076 Bordeaux Cedex, France. Tel: +33 5 56 79 55 10; fax: +33 5 56 79 56 73.

© 2008 Lippincott Williams & Wilkins, Inc.