| Publication Abstract Display | | Type: Published Abstract | | Title: Relative frequency of drug resistance mutations on individual HIV-1 genomes in HAND. | | Authors: Evering T, St. Bernard L, Abolade J, Mohri H, Markowitz M | | Year: 2016 | | Publication: Annual Conference on Retroviruses and Opportunistic Infections | | Volume: Issue: Pages: | | Abstract:Background:
The ability of the CNS to act as sanctuary may result in discordant drug-resistance mutations (DRMs) in
CSF and plasma. Compartmentalization and independent evolution of DRMs in CSF HIV-1 variants has
been described. We hypothesized that in those with HAND differences in the relative frequency of DRMs
in the CSF and plasma would be observed.
Methods:
We used SGA to study paired CSF and plasma samples of 12 HIV+ subjects from the CHARTER study
with no neurocognitive impairment (NCN) (N=5), asymptomatic neurocognitive impairment (ANI) (N=4),
mild neurocognitive disease (MND) (N=2) and HIV-associated dementia (HAD) (N=1). Subjects were
viremic and on treatment at the time of sampling. The Stanford HIVdb program and phylogenetic analyses
were used to identify HIV-1 DRMs on each SGA-derived genome and determine viral
compartmentalization respectively.
Results:
On average, 25 SGS were analyzed per compartment per subject (N=621). We found statistical evidence of
compartmentalization between CSF- and plasma-derived viruses (p<0.05) in individuals with NCN
(2/5=40%) and HAND (5/7=71%). HIV-1 DRMs were commonly found, with 11/12 (92%) subjects with at
least 1 DRM in the CSF or plasma (median 7, range 1-18). Multiple DRMs were commonly identified on
SGA-derived genomes (range 0-6). For all subjects with NCN, the relative frequency of each DRM was
statistically similar between compartments. In contrast, in subjects with HAND, 57% (4/7) of individuals
demonstrated statistically significant differences in the relative frequency of at least one DRM in the CSF
and plasma (Bonferroni corrected p-value thresholds from p<0.0028 to p<0.0125). This represents a trend
toward a statistical difference in the relative frequency of discordant DRMs in the CSF and plasma in those
with NCN and HAND (p=0.08 by Fisher’s exact test). When identified, the relative difference in DRMs
reflects a higher percentage of DRMs in the plasma as opposed to the CSF (21 events vs. 1, p<0.0001 by
Fisher’s exact test). 3 subjects with HAND (3/7=43%) demonstrated one DRM in the CSF that was not
identified in paired plasma. Longitudinal analyses of 2 subjects with HAND reveal the development of
significant differences in the relative frequency of DRMs in the CSF and plasma over time - both in the
presence (N=1) and absence (N=1) of changes in the cART regimen.
Conclusions :
Using SGA, statistically significant differences in the frequency of DRMs in the CSF and plasma are
readily found in those with HAND. |
return to publications listing
|