DURBAN, SOUTH AFRICA – Extended-release naltrexone provides clinically meaningful benefits in HIV-infected prisoners with alcohol use disorder and multiple comorbid conditions as they transition back into the community, according to the findings of a double-blind randomized clinical trial.
“I think it’s important to know that a very effective medication, which has not previously been given to this population, was accepted by this group. It may be a feasible conduit to care as they transition to the community, even among those with severe psychosocial disparities like homelessness and mental illness,” Sandra A. Springer, MD, said in presenting the study findings at the 21st International AIDS Conference.
Extended-release naltrexone (Vivitrol) is a mu-opioid receptor antagonist approved for the treatment of alcohol use disorder, where it has been shown to decrease consumption. But prior to her study, the once-monthly injectable drug hadn’t been studied in alcohol-dependent prisoners living with HIV who are transitioning from jail or prison into the community, noted Dr. Springer, an infectious disease specialist at Yale University in New Haven, Conn.
This is a large, important, and seriously neglected patient population, she observed. The United States has the highest incarceration rate in the world. The prevalence of HIV infection is at least three times greater in U.S. criminal justice settings than in the general population. Alcohol use disorders are eightfold more common. Release from prison or jail in affected individuals often is complicated by relapse to alcohol use, which in turn is associated with poor HIV treatment outcomes.
Dr. Springer reported on 100 HIV-positive adult prisoners with alcohol use disorder diagnosed by DSM-IV criteria who were randomized double-blind two-to-one to 6 monthly 380-mg intramuscular injections of extended-release naltrexone or placebo, with the first dose given 3-7 days prior to release. Participants were required to have no baseline clinical evidence of cirrhosis or very high liver enzyme levels.
Half of participants had chronic hepatitis C. Eighty-seven percent of subjects scored 20 or higher on the Alcohol Use Disorders Identification test, indicating alcohol dependence. On the Mini International Neuropsychiatric Interview, 15% of participants met criteria for major depressive disorder, 16% for bipolar disorder, 59% for cocaine use disorder, 16% for narcotic use disorder, and 16% for cannabis use disorder. Most of the subjects were homeless or had an unstable housing situation.
Alcohol outcomes were assessed monthly during the 6-month trial. Not surprisingly, the better the treatment adherence, the better the outcomes. During the 90 days before incarceration, patients self-reported that 70% of those days were heavy drinking days, defined in men as having five or more drinks per day and in women as four or more. Their average consumption on those heavy drinking days was 28 drinks per day. In contrast, patients who accepted four or more extended-release naltrexone injections during 180 days of follow-up after release from custody drank heavily on just 7.6% of days, with an average of 8.6 drinks per day on those heavy drinking days. Subjects who received four or more placebo injections drank heavily on 11.6% of days, consuming an average of 12 drinks per heavy drinking day.
The time to first heavy drinking day was longer in patients who accepted 4-6 monthly injections of extended-release naltrexone than in those with 4-6 placebo injections. However, the difference achieved statistical significance only in the younger subgroup of participants aged 21-29 years. In that subgroup, the average time to the first heavy drinking day was 24.1 days, compared with 9.5 days with placebo.
On a composite alcohol consumption index comprised of time to first heavy drinking day after release, mean number of drinks per drinking day, change from before to after incarceration in average number of drinks per drinking day, alcohol craving score, and total number of drinking days, subjects who received four or more extended-release naltrexone injections had a significantly more favorable result, with a mean score of 3.15, compared with 2.93 in patients who took four or more placebo injections.
Moreover, consistent use of extended-release naltrexone was associated with significantly lower HIV viral load counts, compared with placebo-treated controls.
Treatment with extended-release naltrexone was safe. No serious side effects occurred, even in patients with comorbid hepatitis C who were on antiretroviral therapy. The most common side effects were the same as in seen in studies of the drug in other populations: mild to moderate nausea, headache, decreased appetite, fatigue, and dizziness.
Elsewhere at AIDS 2016, Chris Beyrer, MD, president of the International AIDS Society, included prisoners on his list of the populations most vulnerable to HIV because of discriminatory laws and policies in many parts of the world. Others on the list were transgender people, sex workers, men who have sex with men, and injection drug users.