Abstract:
:The impact of antiretroviral therapy (ART) on the genetics of simian immunodeficiency virus (SIV) or human immunodeficiency virus (HIV) populations has been incompletely characterized. We analyzed SIV genetic variation before, during, and after ART in a macaque model. Six pigtail macaques were infected with an SIV/HIV chimeric virus, RT-SHIV(mne), in which SIV reverse transcriptase (RT) was replaced by HIV-1 RT. Three animals received a short course of efavirenz (EFV) monotherapy before combination ART was started. All macaques received 20 weeks of tenofovir, emtricitabine, and EFV. Plasma virus populations were analyzed by single-genome sequencing. Population diversity was measured by average pairwise difference, and changes in viral genetics were assessed by phylogenetic and panmixia analyses. After 20 weeks of ART, viral diversity was not different from pretherapy viral diversity despite more than 10,000-fold declines in viremia, indicating that, within this range, there is no relationship between diversity and plasma viremia. In two animals with consistent SIV RNA suppression to <15 copies/ml during ART, there was no evidence of viral evolution. In contrast, in the four macaques with viremias >15 copies/ml during therapy, there was divergence between pre- and during-ART virus populations. Drug resistance mutations emerged in two of these four animals, resulting in virologic failure in the animal with the highest level of pretherapy viremia. Taken together, these findings indicate that viral diversity does not decrease with suppressive ART, that ongoing replication occurs with viremias >15 copies/ml, and that in this macaque model of ART drug resistance likely emerges as a result of incomplete suppression and preexisting drug resistance mutations.
journal_name
J Viroljournal_title
Journal of virologyauthors
Kearney M,Spindler J,Shao W,Maldarelli F,Palmer S,Hu SL,Lifson JD,KewalRamani VN,Mellors JW,Coffin JM,Ambrose Zdoi
10.1128/JVI.01701-10subject
Has Abstractpub_date
2011-01-01 00:00:00pages
1067-76issue
2eissn
0022-538Xissn
1098-5514pii
JVI.01701-10journal_volume
85pub_type
杂志文章abstract::The antiviral activity of the double-stranded complex poly(rI) . poly(rC) in cell culture was restored or even surpassed if the constituent homopolymers were administered separately. Poly(rI) primed the cells for the antiviral activity of poly(rC) and poly(rC) primed for poly(rI), but neither poly(rI) nor poly(rC) pri...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.9.5.721-731.1972
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.12.5875-5881.2002
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.7.3906-3910.1991
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journal_title:Journal of virology
pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.32.1.30-39.1979
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journal_title:Journal of virology
pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.7.5787-5794.1999
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.9.5278-5286.1995
更新日期:1995-09-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.14.5.1307-1309.1974
更新日期:1974-11-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.9.5550-5559.1995
更新日期:1995-09-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.11.6909-6917.2005
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pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Journal of virology
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.62.7.2512-2515.1988
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journal_title:Journal of virology
pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.36.1.254-263.1980
更新日期:1980-10-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.10.3.425-432.1972
更新日期:1972-09-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.32.1.8-18.1979
更新日期:1979-10-01 00:00:00