Pharmacogenetic Associations with ADME Variants and Virologic Response to an Initial HAART Regimen in HIV-Infected Women.

BACKGROUND: Clinical response to highly active antiretroviral therapy (HAART) varies among different populations. A portion of this variability may be due to variation in genes involved in the absorption, distribution, metabolism, and excretion (ADME) of HAART. DESIGN: To identify genetic factors involved in virologic responses to HAART, 13 genes in ADME pathways were analyzed in a cohort of HIV-infected women on HAART. A total of 569 HIV-positive participants from the Women's Interagency HIV Study who initiated HAART from 1994-2012 and had genotype data were included in these analyses. METHODS: Admixture maximum likelihood burden testing was used to evaluate gene-level associations between common genetic variation and virologic response (achieving <80 viral copies/mL) to HAART overall and with specific drug classes. Results: Six statistically significant (P<0.05) gene-level burden tests were observed with response to specific regimen types. CYP2B6, CYP2C19 and CYP2C9 were significantly associated with response to protease inhibitor (PI)-based regimens. CYP2C9, ADH1A and UGT1A1 were significantly associated with response to triple nucleoside reverse transcriptase inhibitor (NRTI) treatment. CONCLUSIONS: Although no genome-wide associations with virologic response to HAART overall were detected in this cohort of HIV-infected women, more statistically significant gene-level burden tests were observed than would be expected by chance (two and a half expected, six observed). It is likely that variation in one of the significant genes is associated with virologic response to certain HAART regimens. Further characterization of the genes associated with response to PI-based treatment is warranted.

Correlates of consistent condom use with main partners by partnership patterns among young adult male injection drug users from five US cities.

This paper examined correlates of consistent condom use with a main partner among heterosexual male injection drug users (IDUs). Using data from a multi-site sample of young IDUs, we identified 1770 sexually active men of whom 24% (429/1770) reported an exclusive main female sex partner and 49% (862/1770) reported both main and casual female sex partners. Consistent condom use with a main partner was low among men with an exclusive main partner and those with multiple partners (12% and 17%, respectively). In multivariate analysis, consistent condom use with a main partner across partnership patterns was directly associated with anticipating a positive response to requests for condom use and by partner support of condom use; consistent condom use was inversely associated with a main partner's pregnancy desires. Among men with an exclusive main partner, consistent condom use was also inversely associated with needle sharing with a main partner. Among men with multiple partners, consistent condom use with a main partner was inversely associated with injecting with a used needle and intimate partner violence. The low prevalence of consistent condom use with main female partners among heterosexually active male IDUs indicates an increased risk for HIV transmission between men and their primary sex partners. Interventions for heterosexual males that are geared toward increasing condom use in primary relationships are warranted.

Factors associated with interest in initiating treatment for hepatitis C Virus (HCV) infection among young HCV-infected injection drug users.

OBJECTIVE: We sought to identify factors associated with interest in receiving therapy for hepatitis C virus (HCV) infection among HCV-infected injection drug users (IDUs) in 3 United States cities. METHODS: IDUs aged 18-35 years who were HCV-infected and seronegative for human immunodeficiency virus underwent surveys on behaviors, experience, and interest in treatment for HCV infection and readiness to quit drug use. RESULTS: Among treatment-naive IDUs (n=216), 81.5% were interested in treatment for HCV infection, but only 27.3% had seen a health-care provider since receiving a diagnosis of HCV infection. Interest in treatment for HCV infection was greater among IDUs with a high perceived threat of progressive liver disease, those with a usual source of care, those without evidence of alcohol dependence, and those with higher readiness scores for quitting drug use. Interest in treatment for HCV infection was 7-fold higher among IDUs who were told by their health-care provider that they were at risk for cirrhosis or liver cancer. CONCLUSIONS: Improving provider-patient communication and integrating treatments for substance abuse and HCV may increase the proportion of IDUs who initiate treatment for HCV infection.