Balduin, Melanie; Oette, Mark; Däumer, Martin P.; Hoffmann, Daniel; Pfister, Herbert J.; Kaiser, Rolf:

Prevalence of minor variants of HIV strains at reverse transcriptase position 103 in therapy-naïve patients and their impact on the virological failure

In: Journal of Clinical Virology, Jg. 45 (2009) ; Nr. 1, S. 34 - 38
Zeitschriftenaufsatz / Fach: Medizin
Abstract:
Abstract
Background and objectives

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.
Study design

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.

Keywords: Minority resistance; Therapy-naïve patients; Non-nucleoside reverse transcriptase inhibitors

Abbreviations: RT, reverse transcriptase; NNRTI, non-nucleoside reverse transcriptase inhibitors; NRTI, nucleoside reverse transcriptase inhibitors; HAART, highly active-antiretroviral-therapy; PCR, polymerase chain reaction; wt, wild type; PI, protease inhibitor; S.D., standard deviation