title: Direct and Indirect Effects of Heavy Alcohol Use on Clinical Outcomes in a Longitudinal Study of HIV Patients on ART.
abstract: In a cohort of patients receiving care for HIV, we examined longitudinally the impact of past 30-day frequency of heavy drinking (consuming 5+ drinks on one occasion) on HIV-related (detectable viral load and CD4+ T cell count) and non-HIV-related (hemoglobin and biomarkers of kidney function and liver fibrosis) clinical outcomes and the extent to which these effects were due to reduced antiretroviral therapy (ART) adherence. Data came from the Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy. Between March 2004 and June 2006, 533 individuals receiving ART were recruited and followed every 6 months for six years. Using longitudinal mediation analysis, we estimated natural direct effects (NDE) of heavy drinking frequency (never, 1-3 times, or 4+ times in the past 30 days) on clinical outcomes and natural indirect effects (NIE) mediated via ART adherence. A one-level increase in heavy drinking frequency had a significant negative NDE on CD4+ T-cell counts (-10.61 cells/mm3; 95 % CI [-17.10, -4.12]) and a significant NIE through reduced ART adherence of -0.72 cells/mm3(95 % CI [-1.28, -0.15]), as well as a significant NIE on risk of detectable viral load (risk ratio = 1.03; 95 % CI [1.00, 1.05]). Heavy drinking had a significant detrimental NIE on a combined index of 5-year mortality risk and detrimental NDE and total effect on a biomarker of liver fibrosis. Heavy drinking has deleterious effects on multiple clinical outcomes in people living with HIV, some of which are mediated through reduced ART adherence.
authors.affiliation: Center for Alcohol and Addiction Studies, Brown University School of Public Health, Box G-S121-4, Providence, RI, 02912, USA. Christopher_Kahler@brown.edu.
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Kahler
authors.affiliation: Center for Statistical Sciences, Brown University School of Public Health, Providence, RI, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.affiliation: Center for Alcohol and Addiction Studies, Brown University School of Public Health, Box G-S121-4, Providence, RI, 02912, USA.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Cioe
authors.affiliation: Department of Clinical and Health Psychology, University of Florida, Gainesville, FL, USA.
authors.forename: Vaughn
authors.initials: V
authors.lastname: Bryant
authors.affiliation: Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA.
authors.forename: Megan M
authors.initials: MM
authors.lastname: Pinkston
authors.affiliation: Department of Infectious Disease, Brown University, Providence, RI, USA.
authors.forename: Erna M
authors.initials: EM
authors.lastname: Kojic
authors.affiliation: Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Nur
authors.initials: N
authors.lastname: Onen
authors.affiliation: Division of Infectious Diseases, Hennepin County Medical Center, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Jason V
authors.initials: JV
authors.lastname: Baker
authors.affiliation: Denver Infectious Disease Consultants, Denver, CO, USA.
authors.forename: John
authors.initials: J
authors.lastname: Hammer
authors.affiliation: Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: John T
authors.initials: JT
authors.lastname: Brooks
authors.affiliation: Division of Global Health Protection, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Pragna
authors.initials: P
authors.lastname: Patel
mesh_terms: D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000453:epidemiology* / Q000276:immunology / Q000378:metabolism; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015415:Biomarkers; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes; D005260:Female; D005919:Glomerular Filtration Rate; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000821:virology; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007677:Kidney Function Tests; D008111:Liver Function Tests; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D019562:Viral Load; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D015415:Biomarkers; D006454:Hemoglobins
keywords: Adherence; Alcohol; HIV; Liver function; VACS Index; Viral load