Limited evolution of inferred HIV-1 tropism while viremia is undetectable during standard HAART therapy.
BACKGROUND:HIV patients on suppressive antiretroviral therapy have undetectable viremia making it impossible to screen plasma HIV tropism if regimen change is required during suppression. We investigated the prevalence and predictors of tropism switch from CCR5-using ("R5") to non-CCR5-usi...
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doaj-d100e8fd2e2b4f1486b03c03023ecbdc2020-11-24T21:56:45ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0196e9900010.1371/journal.pone.0099000Limited evolution of inferred HIV-1 tropism while viremia is undetectable during standard HAART therapy.Guinevere Q LeeWinnie DongTheresa MoDavid J H F KnappChanson J BrummeConan K WoodsSteve KantersBenita YipP Richard HarriganBACKGROUND:HIV patients on suppressive antiretroviral therapy have undetectable viremia making it impossible to screen plasma HIV tropism if regimen change is required during suppression. We investigated the prevalence and predictors of tropism switch from CCR5-using ("R5") to non-CCR5-using ("non-R5") before and after viral suppression in the initially therapy-naïve HOMER cohort from British Columbia, Canada. METHODS:We compared pre-therapy and post-suppression viral genotypic tropism in patients who initiated on PI/NNRTI-based antiretroviral regimens between 1996-1999 (n = 462). Virologic suppression was defined as having two consecutive viral loads of <500 copies/mL, which was the sensitivity limit of most viral load assays at the time. Viral tropism was inferred by V3-loop-population-sequencing and geno2pheno[coreceptor] with cutoff at 5.75% false positive rate (FPR). RESULTS:When virologic suppression was defined as two-consecutive viral loads <500 copies/mL, 34 (9%) of the 397 patients with pre-therapy R5-virus switched to non-R5 at viral load rebound after a median of 19 months (IQR 8-41 months) of undetectable viremia. Duration of viral load suppression was not a predictor of switch, but lower CD4 count during suppression (median 400 versus 250 cells/mL) and an increased prevalence of pre-therapy non-R5 HIV by "deep" sequencing (median 0.2% versus 3.2%) were independently associated with switch (p = 0.03 and p<0.0001, respectively). CONCLUSION:R5-to-non-R5 tropism switches in plasma virus after undetectable viremia were relatively rare events especially among patients with higher CD4 counts during virologic suppression. Our study supports the use of pre-suppression tropism results if maraviroc is being considered during virologic suppression in this subgroup of patients.http://europepmc.org/articles/PMC4048224?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Guinevere Q Lee Winnie Dong Theresa Mo David J H F Knapp Chanson J Brumme Conan K Woods Steve Kanters Benita Yip P Richard Harrigan |
spellingShingle |
Guinevere Q Lee Winnie Dong Theresa Mo David J H F Knapp Chanson J Brumme Conan K Woods Steve Kanters Benita Yip P Richard Harrigan Limited evolution of inferred HIV-1 tropism while viremia is undetectable during standard HAART therapy. PLoS ONE |
author_facet |
Guinevere Q Lee Winnie Dong Theresa Mo David J H F Knapp Chanson J Brumme Conan K Woods Steve Kanters Benita Yip P Richard Harrigan |
author_sort |
Guinevere Q Lee |
title |
Limited evolution of inferred HIV-1 tropism while viremia is undetectable during standard HAART therapy. |
title_short |
Limited evolution of inferred HIV-1 tropism while viremia is undetectable during standard HAART therapy. |
title_full |
Limited evolution of inferred HIV-1 tropism while viremia is undetectable during standard HAART therapy. |
title_fullStr |
Limited evolution of inferred HIV-1 tropism while viremia is undetectable during standard HAART therapy. |
title_full_unstemmed |
Limited evolution of inferred HIV-1 tropism while viremia is undetectable during standard HAART therapy. |
title_sort |
limited evolution of inferred hiv-1 tropism while viremia is undetectable during standard haart therapy. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2014-01-01 |
description |
BACKGROUND:HIV patients on suppressive antiretroviral therapy have undetectable viremia making it impossible to screen plasma HIV tropism if regimen change is required during suppression. We investigated the prevalence and predictors of tropism switch from CCR5-using ("R5") to non-CCR5-using ("non-R5") before and after viral suppression in the initially therapy-naïve HOMER cohort from British Columbia, Canada. METHODS:We compared pre-therapy and post-suppression viral genotypic tropism in patients who initiated on PI/NNRTI-based antiretroviral regimens between 1996-1999 (n = 462). Virologic suppression was defined as having two consecutive viral loads of <500 copies/mL, which was the sensitivity limit of most viral load assays at the time. Viral tropism was inferred by V3-loop-population-sequencing and geno2pheno[coreceptor] with cutoff at 5.75% false positive rate (FPR). RESULTS:When virologic suppression was defined as two-consecutive viral loads <500 copies/mL, 34 (9%) of the 397 patients with pre-therapy R5-virus switched to non-R5 at viral load rebound after a median of 19 months (IQR 8-41 months) of undetectable viremia. Duration of viral load suppression was not a predictor of switch, but lower CD4 count during suppression (median 400 versus 250 cells/mL) and an increased prevalence of pre-therapy non-R5 HIV by "deep" sequencing (median 0.2% versus 3.2%) were independently associated with switch (p = 0.03 and p<0.0001, respectively). CONCLUSION:R5-to-non-R5 tropism switches in plasma virus after undetectable viremia were relatively rare events especially among patients with higher CD4 counts during virologic suppression. Our study supports the use of pre-suppression tropism results if maraviroc is being considered during virologic suppression in this subgroup of patients. |
url |
http://europepmc.org/articles/PMC4048224?pdf=render |
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