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HIV type 1 polymerase gene polymorphisms are associated with phenotypic differences in replication capacity and disease progression.

ABSTRACT: Determinants of intersubtype differences in human immunodeficiency virus type 1 (HIV-1) clinical disease progression remain unknown.HIV-1 subtype was independently determined for 5 separate genomic regions in 396 HIV-1 seroconverters from Rakai, Uganda, using a multiregion hybridization assay. Replication capacities (RC) in samples from a subset of 145 of these subjects were determined. HIV-1 genomic regions and pol RC were examined for association with disease progression. Amino acid polymorphisms were examined for association with pol RC.In multivariate analyses, the hazard for progression to the composite end point (defined as a CD4(+) T-cell count <250 cells/mm(3), antiretroviral therapy initiation, or death) among patients with subtype D pol infection was 2.4 times the hazard for those infected with subtype A pol infection (P = .001). Compared with subtype A pol (the reference group), the hazard for progression to the composite end point for subtype D pol infection with a pol RC >67% (ie, the median pol RC) was significantly greater (HR, 4.6; 95% confidence interval [CI], 1.9-11.0; P = .001), whereas the hazard for progression to the composite end point for subtype D pol infection with a pol RC ?67% was not significantly different (HR, 2.2; 95% CI, 1.0-4.9; P = .051). Amino acid substitutions at protease positions 62 and 64 and at reverse transcriptase position 272 were associated with significant differences in pol RC.HIV-1 pol gene intersubtype and RC differences are associated with disease progression and may be influenced by amino acid polymorphisms.

SUBMITTER: Ng OT

PROVIDER: S-EPMC3864385 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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HIV type 1 polymerase gene polymorphisms are associated with phenotypic differences in replication capacity and disease progression.

Ng Oon Tek OT Laeyendecker Oliver O Redd Andrew D AD Munshaw Supriya S Grabowski Mary K MK Paquet Agnes C AC Evans Mark C MC Haddad Mojgan M Huang Wei W Robb Merlin L ML Reynolds Steven J SJ Gray Ronald H RH Wawer Maria J MJ Serwadda David D Eshleman Susan H SH Quinn Thomas C TC

The Journal of infectious diseases 20130806 1

<h4>Background</h4>Determinants of intersubtype differences in human immunodeficiency virus type 1 (HIV-1) clinical disease progression remain unknown.<h4>Methods</h4>HIV-1 subtype was independently determined for 5 separate genomic regions in 396 HIV-1 seroconverters from Rakai, Uganda, using a multiregion hybridization assay. Replication capacities (RC) in samples from a subset of 145 of these subjects were determined. HIV-1 genomic regions and pol RC were examined for association with disease ...[more]

PMID: 23922373

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HIV type 1 polymerase gene polymorphisms are associated with phenotypic differences in replication capacity and disease progression.

Publications

HIV type 1 polymerase gene polymorphisms are associated with phenotypic differences in replication capacity and disease progression.

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