Prevalence and Impact of Minority Variant Drug Resistance Mutations in Primary HIV-1 InfectionReport as inadecuate




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Objective

To evaluate minority variant drug resistance mutations detected by the oligonucleotide ligation assay OLA but not consensus sequencing among subjects with primary HIV-1 infection.

Design-Methods

Observational, longitudinal cohort study. Consensus sequencing and OLA were performed on the first available specimens from 99 subjects enrolled after 1996. Survival analyses, adjusted for HIV-1 RNA levels at the start of antiretroviral ARV therapy, evaluated the time to virologic suppression HIV-1 RNA<50 copies-mL among subjects with minority variants conferring intermediate or high-level resistance.

Results

Consensus sequencing and OLA detected resistance mutations in 5% and 27% of subjects, respectively, in specimens obtained a median of 30 days after infection. Median time to virologic suppression was 110 IQR 62–147 days for 63 treated subjects without detectable mutations, 84 IQR 56–109 days for ten subjects with minority variant mutations treated with ≥3 active ARVs, and 104 IQR 60–162 days for nine subjects with minority variant mutations treated with <3 active ARVs p = .9. Compared to subjects without mutations, time to virologic suppression was similar for subjects with minority variant mutations treated with ≥3 active ARVs aHR 1.2, 95% CI 0.6–2.4, p = .6 and subjects with minority variant mutations treated with <3 active ARVs aHR 1.0, 95% CI 0.4–2.4, p = .9. Two subjects with drug resistance and two subjects without detectable resistance experienced virologic failure.

Conclusions

Consensus sequencing significantly underestimated the prevalence of drug resistance mutations in ARV-naïve subjects with primary HIV-1 infection. Minority variants were not associated with impaired ARV response, possibly due to the small sample size. It is also possible that, with highly-potent ARVs, minority variant mutations may be relevant only at certain critical codons.



Author: Joanne D. Stekler , Giovanina M. Ellis, Jacquelyn Carlsson, Braiden Eilers, Sarah Holte, Janine Maenza, Claire E. Stevens, Ann C.

Source: http://plos.srce.hr/



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