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

Abstract

BACKGROUND:

Determinants of intersubtype differences in human immunodeficiency virus type 1 (HIV-1) clinical disease progression remain unknown.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

HIV-1 pol gene intersubtype and RC differences are associated with disease progression and may be influenced by amino acid polymorphisms.

• Authors: Oon Tek Ng, Oliver Laeyendecker, Andrew D Redd, Supriya Munshaw, Mary K Grabowski, Agnes C Paquet, Mark C Evans, Mojgan Haddad, Wei Huang, Merlin L Robb, Steven J Reynolds, Ronald H Gray, Maria J Wawer, David Serwadda, Susan H Eshleman, Thomas C Quinn
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 209 Issue 1 Pg. 66-73 (Jan 01 2014) ISSN: 1537-6613 [Electronic] United States
• PMID: 23922373 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)

Topics

• Adolescent
• Adult
• Amino Acid Substitution
• Disease Progression
• Female
• Genes, pol
• HIV Infections (virology)
• HIV-1 (enzymology, genetics, physiology)
• Humans
• Male
• Middle Aged
• Phenotype
• Uganda
• Viral Load
• Virus Replication (genetics)