| Publication Abstract Display | | Type: Published Manuscript | | Title: No substantial evidence for sexual transmission of minority HIV drug resistance mutations in men who have sex with men. | | Authors: Chaillon A, Nakazawa M, Wertheim J, Little S, Smith D, Mehta S, Gianella S | | Year: 2017 | | Publication: Journal of Virology | | Volume: 91 Issue: 21 Pages: | | Abstract:During primary HIV-infection, the presence of minority drug resistant mutations (DRM) may be a consequence of sexual transmission, de novo mutations or technical errors. Baseline blood samples were collected from 24 HIV-infected antiretroviral-naive, genetically- and epidemiologically- linked source and recipient partners, shortly after the recipient's estimated date of infection. An additional 32 longitudinal samples were available from 11 recipients. Deep-sequencing of HIV reverse transcriptase (RT) was performed (Roche/454) and screened for nucleoside and non-nucleoside RT inhibitor DRM. The likelihood of sexual transmission and persistence of DRM was assessed using Bayesian-based statistical modeling. While majority DRM (>20%) were consistently transmitted from source to recipient, the probability to detect a minority DRM in the recipient was not increased when the same minority DRM was detected in the source (Bayes Factor, BF=6.37). Longitudinal analyses revealed an exponential decay of DRM (BF=0.05) while genetic diversity increased. Our analysis revealed no substantial evidence for sexual transmission of minority DRM. The presence of minority DRM during early infection, followed by a rapid decay is consistent with the "mutation-selection balance" hypothesis, in which deleterious mutations are more efficiently purged later during HIV infection when the larger effective population size allows more efficient selection. Future studies using more recent sequencing technologies that are less prone to single-base errors should confirm these results applying a similar Bayesian framework in other clinical settings.IMPORTANCE The advent of sensitive sequencing platforms has led to an increased identification of minority drug resistance mutations (DRM), including among antiretroviral therapy-naïve HIV-infected individuals. While transmission of DRM may impact future therapy options for newly infected individuals, the clinical significance of the detection of minority DRMs remains controversial. In the present study, we applied deep sequencing techniques within a Bayesian hierarchical framework to a cohort of 24 transmission pairs to investigate whether minority DRMs detected shortly after transmission were the consequence of: (i) sexual transmission from the source, (ii) de novo emergence shortly after infection followed by viral selection and evolution or (iii) technical errors/limitations of deep sequencing methods. We found no clear evidence to support the sexual transmission of minority resistant variants and our results suggested that minor resistant variants may emerge de novo shortly after transmission when the small effective population size limits efficient purge by natural selection. |
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