Specific protease mutation patterns are associated with oropharyngeal candidiasis in a New Orleans patient cohort of HIV-infected individuals|
Peter J. Hickman1 Robertino M. Mera; Janet E. Leigh; Paul L. Fidel Jr.; Allen R. Mock; William R. Gallaher & Ronald B. Luftig
HIV-1 protease gene sequences were obtained from peripheral blood, saliva or oral tissues of 35 HIV+ patients using nested amplification and manual sequencing of PCR products. Of the 35 HIV+ patients 9 had clinical oropharyngeal candidiasis (OPC) while 26 did not, and only 4 patients were on protease inhibitor (PI) therapy. These patients were collected prior to major use of HAART therapy in New Orleans, Louisiana. Analysis of 172 amino acid sequences revealed unique patterns of mutation that were in most cases independent of the type of cell from which DNA was isolated and were, instead, primarily dependent on the individual patient. Principal component analysis indicated that approximately 50% of the variance of the amino acid replacements could be explained by patterns of change seen in only five patients. Significantly, 4 of these 5 patients were OPC+ indicating that patients with OPC are more likely to express a principal mutation pattern than patients without OPC (p = 0.002, Chi square). Dendrograms revealed that these five patients clustered separately from each other and from HIV-1LAI suggesting that principal mutation patterns as well as OPC are independent of viral evolution. In conclusion, prior to widespread use of PI therapy to combat HIV-1, patients with OPC exhibited unique patterns of amino acid replacements within the HIV-1 protease.
HIV-1, mutation, proteases, candidiasis