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

2. 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?

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

5. 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

6. Uniform Assessments

7. 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

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

9. 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

10. 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

11. Decreasing Alcohol With Naltrexone
Project DAWN
Decreasing Alcohol With Naltrexone

12. 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)

13. 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

14. 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

15. 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.

16. 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)

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

18. 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