14th Conference on Retroviruses and Opportunistic Infections Los Angeles, California - February 25-28, 2007

Conf Retrovir Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 3e)

David Haas
Vanderbilt Univ Sch of Med, Nashville, TN, US

BACKGROUND: Antiretroviral medications greatly reduce morbidity and mortality in persons living with HIV/AIDS, but drug toxicity limits treatment success in many individuals. The field of pharmacogenomics seeks to understand the influence of human genetic variants in response to medications. Investigators worldwide have begun to identify associations among human genetic variants, predisposition to HIV drug toxicities, and likelihood of virologic failure. Pharmacogenomics also holds immense promise to identify novel targets for drug development. The seminal discovery that a naturally occurring, nonfunctional variant of the HIV receptor gene CCR5 protected against HIV infection fostered the development of CCR5 antagonists. Numerous laboratory methods are now available for rapidly identifying genetic variability, and technological advances of genomic analysis are progressing at a rapid pace. However, deciphering relationships between such variants and clinical outcomes during HIV disease and its therapy remains a daunting task, and often requires large sample sizes. Investigators must establish and utilize large DNA banks linked to cohorts and clinical trials to allow future unplanned analyses. Several groups have well-established, stored DNA sample repositories that have been used to explore relationships between human genetics and variable response to HIV therapy.

CONCLUSIONS: Because of the well-recognized risk of false discovery due to multiple comparisons in high-throughput human genomic association studies, such repositories are critical both for the initial identification of potential genotype-phenotype associations, and for validation of initial putative associations. Through continued translational and applied research, pharmacogenomics will ultimately benefit persons living with HIV worldwide by identifying new targets for novel therapeutics, through individualized drug prescribing that is informed by human genetic testing, and by anticipating the likely frequency of adverse treatment events among diverse populations worldwide based on knowledge of genetic architecture.

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2007-02-25
3e

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