Prevalence of minor variants of HIV strains at reverse transcriptase position 103 in therapy-naïve patients and their impact on the virological failure.
OBJECTIVE
Minority HIV-1 populations with resistance mutations might result in therapy failure. The prevalence of transmitted minorities in therapy-naïve patients and their influence on the virological outcome of the first-line-therapy need clarification.


METHODS
The HIV reverse transcriptase (RT) of 159 therapy-naïve patients from the RESINA-cohort was genotyped. The relative amount of RT-K103N was measured by primer specific PCR. The response to first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-therapy was evaluated.


RESULTS
Bulk-sequencing detected 1 NNRTI mutation (no K103N) in six patients (1.26%). K103N minorities were found in 20.1% of the samples, more frequently in HIV-1 non-B subtypes (40.6%) than in subtype B (15.0%) (p=0.0025). NNRTI treatment failed after 12 weeks in 24% of 17 patients with minority, but only in 15% of 67 patients without minority.


CONCLUSIONS
K103N minorities were found in 20.1% of the patients, whereas the prevalence of major K103N populations was 3% in the total RESINA-cohort. K103N minorities were more frequent in non-B subtypes. There is some evidence for a higher risk of NNRTI-treatment failure in patients with K103N minorities; however, the majority of patients with minority underwent a successful first-line-treatment.
Balduin
Melanie
M
Institute of Virology, University of Cologne, Cologne, Germany. melbaldu@gmx.de
Oette
Mark
M
Däumer
Martin P
MP
Hoffmann
Daniel
D
Pfister
Herbert J
HJ
Kaiser
Rolf
R
D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D015331:Cohort Studies; D003627:Data Interpretation, Statistical; D005260:Female; D015751:Genes, pol; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology / Q000821:virology*; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D015995:Prevalence; D012367:RNA, Viral / Q000032:analysis; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D017211:Treatment Failure
D019380:Anti-HIV Agents; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase