Detection of minor populations of drug-resistant HIV-1 in acute seroconverters.
OBJECTIVE
The transmission of drug-resistant HIV-1 is a major health concern. To date, most clinical studies have relied on sequencing techniques for genotypic analyses which do not allow quantification of minority viral populations below 25%. As minor populations of drug-resistant HIV-1 could impact the efficiency of antiretroviral therapy, this study was performed to determine the prevalence of minor populations of drug-resistant HIV-1 in acute seroconverters.


METHODS
Forty-nine acute seroconverters from two clinical centers in Germany were included in the study. Individuals were identified between June 1999 and March 2003, and none had received antiretroviral therapy prior to sampling. Minor populations of drug-resistant variants were detected by quantitative real-time polymerase chain reaction using allele-discriminating oligonucleotides for three key resistance mutations: L90M (protease), K103N and M184V (reverse transcriptase). The approximate discriminative power was between 0.01 and 0.2%.


RESULTS
Drug-resistant variants were detected in 10 of 49 patients (20.4%). The L90M mutation was found in one of 49 (2%), the K103N mutation in five of 49 (10.2%) and the M184V mutation in six of 49 (12.2%) patients, respectively. In five of the 10 individuals with detectable drug-resistant virus (50%), the detected population represented a minor viral quasi-species (< 25% of viruses) and was not detected by direct sequencing.


CONCLUSIONS
The prevalence of minor populations of drug-resistant HIV-1 in acute seroconverters can be frequently detected and may impact the success of antiretroviral therapy.
Metzner
Karin J
KJ
University of Erlangen-Nuremberg, Institute of Clinical and Molecular Virology, Germany. karin.metzner@viro.med.uni-erlangen.de
Rauch
Pia
P
Walter
Hauke
H
Boesecke
Christoph
C
Zöllner
Bernhard
B
Jessen
Heiko
H
Schewe
Knud
K
Fenske
Stefan
S
Gellermann
Holger
H
Stellbrink
Hans-Jürgen
HJ
D000208:Acute Disease; D024882:Drug Resistance, Viral / Q000235:genetics*; D005838:Genotype; D006679:HIV Seropositivity / Q000175:diagnosis* / Q000188:drug therapy; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction