Among HIV risk behaviors, those related to intravenous drug use are the most salient, with sero-conversion rates among intravenous drug users of at least 6.2%. Importantly, other behavioral dimensions, primarily related to impulse control, are correlated, jointly influence HIV infection risk and share an underlying neurobiology. The AIDS Linked to the Intravenous Experience (ALIVE) is a prospective community-based cohort of intravenous drug users (IDUs) in Baltimore that commenced in 1988, eventually enrolling more than 3,500 IDUs. Semi-annual follow-up included comprehensive assessment of risk behaviors and drug use. A separate study, focused on non-behavioral genetic risk for infection performed a genome-wide association study (GWAS) on a subset (N=1197) of the sample. This will allow us, in an existing, large, well-characterized, predominantly African-American sample, to investigate in a genome-wide association framework the contribution of measured genotypes to variation in HIV behavioral risk trajectory defined using drug and other behavioral-risk measures.
In Aim 1, we propose to examine the genetic contribution to class membership in longitudinal intravenous (IV) drug injection trajectories in the already genotyped ALIVE sample. Prior work in this sample has identified unique longitudinal classes of drug injection career.
In Aim 2, we will perform a genome-wide association scan of a novel 'injection years'phenotype designed to capture the length of an injector's career.
In Aim 3, we will generate a novel composite index of HIV-risk behavior, using drug-related and sexual behaviors. We will examine this novel risk metric in a longitudinal framework and perform a GWAS of HIV-risk trajectory class. Our three Specific Aims leverage this unique, existing, NIDA-funded resource to address novel hypotheses regarding the genetics of HIV risk behaviors without the costs of additional genetic assays. This work is novel, innovative, cost effective and likely to identify important genetic contributions to HIV risk trajectory. The examination of longitudinal intravenous (IV) drug injection trajectories and the genome-wide association scan in the ALIVE sample of a novel 'injection years'and composite HIV risk phenotypes is significant because it will inform prevention and treatment strategies and aid in identifying subpopulations or clusters of behaviors that are more amenable to prevention strategies. In short, the research is significant because the results will elucidate our understanding of modifiable and fixed components of HIV behavior risk trajectories in this and other populations, and leads to enhanced efforts at treatment and prevention.
A key step in creating effective HIV prevention strategies is the identification of modifiable and non-modifiable factors that influence risk trajectory. We propose, in an existing, already- genotyped, large (Total N~3500), NIDA-funded, African American sample of intravenous drug users ascertained in Baltimore, MD, a genome-wide association scan of HIV-risk behavior trajectory. Identifying the genetic influences of risk variation will inform future prevention strategies by allowing a greater focus on the components of risk that are easily modifiable.
| Maher, Brion S (2015) Polygenic Scores in Epidemiology: Risk Prediction, Etiology, and Clinical Utility. Curr Epidemiol Rep 2:239-244 |
