Transmission of HIV-1 drug-resistant variants: prevalence and effect on treatment outcome.
BACKGROUND
Human immunodeficiency virus type 1 (HIV-1) drug resistance is an important threat to the overall success of antiretroviral therapy (ART). Because of the limited sensitivity of commercial assays, transmitted drug resistance (TDR) may be underestimated; thus, the effect that TDR has on treatment outcome needs to be investigated. The objective of this study was to investigate the prevalence of TDR in HIV-infected patients and to evaluate the significance of TDR with respect to treatment outcome by analyzing plasma viral RNA and peripheral blood mononuclear cell proviral DNA for the presence of drug resistance mutations.


METHODS
In a prospective study, we investigated the level of TDR in 61 patients by comparing the results of a sensitive multiplex-primer-extension approach (termed HIV-SNaPshot) that is capable of screening for 9 common nucleoside reverse-transcriptase inhibitor and nonnucleotide reverse-transcriptase inhibitor mutations with those of a commercial genotyping kit, ViroSeq (Abbott).


RESULTS
Twenty-two patients were found to carry mutations. More patients with TDR were identified by the HIV-SNaPshot assay than by ViroSeq analysis (33% vs 13%; [P=.015). There was no significant difference in the time from initiation of ART to virological suppression between susceptible patients and those carrying low- or high-level resistance mutations (mean +/- standard deviation, 128 +/- 59.1 vs 164.9 +/- 120.4; P=.147). Furthermore, analyses of CD4 cell counts showed no significant difference between these 2 groups 1 year after the initiation of ART (mean, 184 vs 219 cells/microL; P=.267).


CONCLUSIONS
We found the prevalence of TDR in recently infected ART-naive patients to be higher than that estimated by ViroSeq genotyping alone. Follow-up of patients after treatment initiation showed a trend toward there being more clinical complications for patients carrying TDR, although a significant effect on treatment outcome could not be demonstrated. Therefore, the clinical relevance of low-abundance resistant quasispecies in early infection is still in question.
Jakobsen
Martin R
MR
Department of Infectious Diseases, Aarhus University Hospital, Skejby, Denmark. mrj@burnet.edu.au
Tolstrup
Martin
M
Søgaard
Ole S
OS
Jørgensen
Louise B
LB
Gorry
Paul R
PR
Laursen
Alex
A
Ostergaard
Lars
L
D000328:Adult; D044966:Anti-Retroviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D003718:Denmark / Q000453:epidemiology; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology / Q000635:transmission / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015995:Prevalence; D011446:Prospective Studies; D011533:Proviruses / Q000235:genetics; D018709:Statistics, Nonparametric; D016896:Treatment Outcome; D019562:Viral Load
D044966:Anti-Retroviral Agents