Reducing Heavy Drinking to Optimize HIV/AIDS Treatment and Prevention P.I.: Lynn E. Sullivan, M.D.

Heavy Drinking in HIV-infected individuals Is common: Lifetime prevalence of alcohol use disorders in patients with HIV ranges from 22% to 60% Heavy drinking (>4 drinks for women; >5 drinks for men) seen in 8% to 12% Approximately twice that of the U.S. national average Leads to myriad negative outcomes: Poor highly active antiretroviral (HAART) adherence HIV disease progression Liver damage Increased transmission risk behaviors Increased incidence of viral mutations?

No Data on Treatment No published trials using alcohol pharmacotherapies in patients with HIV!

NIAAA studies of medication in HIV-Infected Heavy Drinkers Sullivan/Brown Injectable naltrexone + Medication Management (MM) Springer/Altice Injectable naltrexone + (MM) upon release from prison McCaul Ondansatron + (MM) in women Cook Naltrexone + (MM) in women

Uniform Assessments

Why Naltrexone? Effective treatment Efficacy demonstrated in specialty settings and primary care Odds ratio for relapse to heavy drinking: 0.62 (95% CI 0.52,0.75) Decreased potential for interactions with antiretroviral medications compared to other medications (see next slide and my next talk). Injectable formulation Well-tolerated Improved adherence Good treatment option for heavy drinkers who do not: Identify themselves as alcohol dependent Have abstinence as a treatment goal

VACS Findings Naltrexone is not associated with hepatotoxicity and does not have a negative impact on biologic parameters in patients receiving HAART

Why Medical Management (Counseling)? Effective treatments (MI, CBT, TSF) Not tested in HIV-infected patients No interactions with antiretroviral medications Well-tolerated Can improve adherence To antiretroviral medications and naltrexone Good treatment option for heavy drinkers who do not: Identify themselves as alcohol dependent Have abstinence as a treatment goal

Aims To examine the impact of injectable NTX and alcohol/HAART adherence counseling on HIV-infected patients with heavy drinking, alcohol abuse or dependence on: HAART adherence Alcohol consumption

Decreasing Alcohol With Naltrexone Project DAWN Decreasing Alcohol With Naltrexone

Study Design: 154 subjects Randomized Double-blind Placebo-controlled 24 weeks with follow-up at 9 and 12 months Injectable NTX vs. placebo Brief psychosocial counseling: Medical Management for alcohol use (Project COMBINE) HAART adherence (Sorensen)

Subjects Inclusion criteria Exclusion criteria HIV-infected individuals Age >18 years Alcohol abuse/dependence or report heavy drinking 4 or more times in the past 4 weeks. Heavy drinking is defined as 4 or more drinks for women and 5 or more drinks for men on an occasion Report less than 95% adherence to their HAART medication Able to understand English and provide informed consent Exclusion criteria Psychotic or severely psychiatrically disabled Medical conditions that would preclude treatment completion or be of harm during the course of the study ALT or AST greater than 5 times the upper limit of the normal range or cirrhosis (Childs-Pugh Class C) Known contraindication to NTX therapy (e.g. opioid medication for pain) Pregnant, nursing or unable to use an effective method of birth control

Treatment Settings New Haven Bronx Yale-New Haven Hospital Nathan Smith HIV Clinic West Haven VA Medical Center HIV Specialty Clinic Bronx VA Medical Center

Counseling Eight sessions Conducted by primary care nurse Manual guided Medical Management (MM) Project COMBINE Incorporates the clinical skills and advice used by primary care practitioners 10 minutes Medication Coaching (MC) Adapted from medication adherence intervention for HIV-infected patients with substance use (Sorensen) Uses strategies to increase HAART medication adherence: Individual adherence management plan Self-monitoring techniques Increasing motivation and self-efficacy Engaging social support Building on adherence skills and client strengths Maintaining adherence Beginning termination Review and planning for future adherence.

Assessments Baseline and weeks 1,2,4,6,8,10,12,16, 20,24 and follow-up at 9 and 12 months HAART adherence (pharmacy fill/refill data, CPCRA HAART medication adherence form, pill counts) (all time points) Alcohol consumption (all time points) Time-Line Follow Back BAC (breathalyzer) Alcohol and drug use (ASI) (monthly) Viral mutations Standard HIV drug resistance testing and ultra-deep sequencing (monthly) CD4 lymphocyte count and HIV RNA (monthly) Hepatotoxicity (AST, ALT, FIB-4) (monthly) HIV risk behaviors (monthly) Side effects (SAFTEE) (weekly, biweekly, monthly) Depressive symptoms (quarterly)

FIB-4 FIB-4 = a non-invasive marker of liver fibrosis

Outcomes The primary study outcome is adherence to HAART medications Secondary study outcomes include: 1) Frequency of heavy drinking 2) HIV viral mutations 3) Change in biological markers CD4 lymphocyte counts HIV RNA 4) Hepatotoxicity 5) Sexual risk behaviors