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.