Impaired human immunodeficiency virus type 1 replicative fitness in atypical viremic non-progressor individuals

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F17%3A00475267" target="_blank" >RIV/61388963:_____/17:00475267 - isvavai.cz</a>

Result on the web

<a href="https://aidsrestherapy.biomedcentral.com/articles/10.1186/s12981-017-0144-0" target="_blank" >https://aidsrestherapy.biomedcentral.com/articles/10.1186/s12981-017-0144-0</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1186/s12981-017-0144-0" target="_blank" >10.1186/s12981-017-0144-0</a>

Result language

angličtina

Original language name

Impaired human immunodeficiency virus type 1 replicative fitness in atypical viremic non-progressor individuals

Original language description

Progression rates from initial HIV-1 infection to advanced AIDS vary significantly among infected individuals. A distinct subgroup of HIV-1-infected individuals--termed viremic non-progressors (VNP) or controllers--do not seem to progress to AIDS, maintaining high CD4(+) T cell counts despite high levels of viremia for many years. Several studies have evaluated multiple host factors, including immune activation, trying to elucidate the atypical HIV-1 disease progression in these patients, however, limited work has been done to characterize viral factors in viremic controllers. We analyzed HIV-1 isolates from three VNP individuals and compared the replicative fitness, near full-length HIV-1 genomes and intra-patient HIV-1 genetic diversity with viruses from three typical (TP) and one rapid (RP) progressor individuals. Viremic non-progressors and typical patients were infected for > 10 years (range 10-17 years), with a mean CD4(+) T-cell count of 472 cells/mm(3) (442-529) and 400 cells/mm(3) (126-789), respectively. VNP individuals had a less marked decline in CD4(+) cells (mean -0.56, range -0.4 to -0.7 CD4(+)/month) than TP patients (mean -10.3, -8.2 to -13.1 CD4(+)/month). Interestingly, VNP individuals carried viruses with impaired replicative fitness, compared to HIV-1 isolates from the TP and RP patients (p < 0.05, 95% CI). Although analyses of the near full-length HIV-1 genomes showed no clear patterns of single-nucleotide polymorphisms (SNP) that could explain the decrease in replicative fitness, both the number of SNPs and HIV-1 population diversity correlated inversely with the replication capacity of the viruses (r = -0.956 and r = -0.878, p < 0.01, respectively). It is likely that complex multifactorial parameters govern HIV-1 disease progression in each individual, starting with the infecting virus (phenotype, load, and quasispecies diversity) and the intrinsic ability of the host to respond to the infection. Here we analyzed a subset of viremic controller patients and demonstrated that similar to the phenomenon observed in patients with a discordant response to antiretroviral therapy (i.e., high CD4(+) cell counts with detectable plasma HIV-1 RNA load), reduced viral replicative fitness seems to be linked to slow disease progression in these antiretroviral-naive individuals.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10607 - Virology

Project

<a href="/en/project/LK11207" target="_blank" >LK11207: The Role of HIV Fitness on Disease Progression in the Absence of Antiretroviral Treatment</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

AIDS Research and Therapy

ISSN

1742-6405

e-ISSN

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Volume of the periodical

14

Issue of the periodical within the volume

Mar 20

Country of publishing house

GB - UNITED KINGDOM

Number of pages

17

Pages from-to

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UT code for WoS article

000397757000001

EID of the result in the Scopus database

2-s2.0-85015618746