Pilot Study of Opioid-receptor Antagonists to Reduce Pain and Inflammation among HIV-Infected Persons with Alcohol Problems

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Pain is a common co-morbidity for HIV-infected patients. Prevalence studies suggest that, on average, half of all HIV-infected persons suffer pain. Chronic pain can lead to heavy alcohol use among HIV-infected persons, which may in turn be a barrier to treatment/control of HIV and contribute to spread of HIV. Thus there is an urgent need to address pain among persons with HIV. Opioid receptor antagonists such as naltrexone and nalmefene, which are licensed for treatment of alcohol use disorders, show promise as being effective and safe treatments for chronic pain among persons with HIV. This study will pilot test novel pharmacotherapies (opioid receptor antagonists) to improve chronic pain among HIV-infected heavy drinkers, and will explore the hypothesis that the mechanism of action for improving pain is through decreased inflammation. The specific aims of the research are: UH2/Aim 1: To assess the feasibility, tolerability and safety of using opioid receptor antagonists (low-dose naltrexone and nalmefene) to treat pain among HIV-infected persons with heavy alcohol use and chronic pain; UH3/Aim 2: to perform a 3-arm pilot randomized, double-blinded, placebo-controlled study of low-dose naltrexone and nalmefene vs. placebo among HIV-infected persons with heavy alcohol use and chronic pain to provide estimates of their effects on: 1) pain (both self-reported and experimental/cold pressor test; 2) inflammation (i.e., levels of inflammatory cytokines IL-6 and TNF-α); and 3) measures of HIV control (CD4 count and viral load). The results of this study will provide preliminary information (tolerability, effect size, etc.) to design a larger RCT of low-dose naltrexone and/or nalmefene for chronic pain among persons with heavy alcohol use. We choose to conduct this research in St. Petersburg, Russia, given that: 1) nalmefene is licensed in Russia, but not currently in the US; 2) patients are seldom on chronic opioids (which are contraindicated to use with opioid receptor antagonists) due to the unavailability of opioid agonist therapy for addiction and restricted use of opioids for pain; and 3) a high prevalence of heavy drinking and HIV exists in Russia. Addressing chronic pain is a high priority for patients with HIV, and therefore this application is highly “patient-centered” as well as innovative. Given the US epidemic of opioid use disorders, new pharmacotherapies without addictive potential are desperately needed for HIV-infected persons with chronic pain and alcohol problems.