URBAN ARCH Investigates Pain among People Living with HIV
In this edition of the URBAN ARCH Newsletter we will highlight updates in URBAN ARCH pain-related research projects among individuals living with HIV. In 2017, we introduced two UH2 studies, which both focused on pain and alcohol use among HIV-positive individuals: Tibor Palfai’s UH2 study, “Internet-based video-conferencing to address alcohol use and pain among heavy drinkers in HIV-care,” and Judith Tsui’s UH2 study, “Pilot study of opioid-receptor antagonists to reduce pain and inflammation among HIV-infected persons with alcohol problems.”
These studies are funded by the UH2/UH3 mechanism, which begins with a two-year UH2 award to develop pre-clinical efficacy studies, and then transitions to a three-year UH3 award for clinical trial planning, contingent upon the goals of the UH2 grant being met. The overarching mission of the studies described here is to conduct interdisciplinary research aimed at addressing pain among people living with HIV (PLWH) who report heavy drinking, and to develop interventions to reduce alcohol use and HIV-related consequences.
Chronic pain and heavy drinking are common co-occurring conditions among PLWH. Each of these conditions has negative impacts on daily function and HIV-related health outcomes. Pain management is a growing issue for HIV-positive individuals, especially those with alcohol use disorders. Chronic pain has been found to lead to heavy alcohol use among HIV-positive people, which is detrimental to the treatment of HIV, as well as the control of its transmission. Therefore, it is important to study pain among HIV-positive heavy drinkers, especially research that focuses on the development of novel treatments.
What has been learned from the UH2 Components?
Dr. Palfai’s UH2 Boston-based study, “Internet-based video-conferencing to address alcohol use and pain among heavy drinkers in HIV-care,” developed and evaluated a video telehealth approach to investigate alcohol use and pain among heavy drinking HIV-positive patients. The study’s main purpose was to test the intervention’s feasibility and acceptability. In the first part of the project, semi-structured interviews were conducted to better understand participant experiences of pain, alcohol use, and treatment within the context of HIV. These interviews provided insight into potential ways to address heavy drinking among PLWH. Interviews also highlighted the importance of addressing emotional stress, stigma and discrimination associated with HIV status, and depressive symptoms as part of the intervention. The second part of the project was an open pilot phase which examined implementation issues such as delivery of the intervention, engagement with the technology, recruitment, assessment, follow-up procedures, and outcome measures. The UH2 project successfully developed a patient-informed intervention to reduce heavy drinking and chronic pain among patients in HIV-care and examined the feasibility of procedures for pilot trial planned for the next phase of this research. Read more about the results of this study here.
Dr. Tsui’s UH2 study, “Pilot study of opioid-receptor antagonists to reduce pain and inflammation among HIV-infected persons with alcohol problems,” assessed the feasibility, tolerability, and safety of two opioid receptor antagonists to improve chronic pain among heavy drinking HIV-positive individuals. This two-arm, randomized, double-blinded study based in St. Petersburg, Russia, examined low-dose naltrexone and the K-opioid antagonist, nalmefene. This study found that low-dose naltrexone was tolerable and safe to use for chronic pain among HIV-positive people with a history of heavy alcohol use. However, nalmefene was not tolerable, as apparent from discontinuation of the medication by participants early on in the study. The UH2 goals were met with assessment of the tolerability and safety of the medications, as well as proof of successful recruitment and retention strategies. Due to the intolerability of nalmefene, the study team decided not to move forward with nalmefene for the UH3 portion, but to replace nalmefene with gabapentin, one of the most commonly prescribed non-narcotic medications for pain, despite only being FDA-approved for “post-herpetic neuralgia.” There is limited literature to support gabapentin’s use in other pain conditions, and generalized chronic pain. However, gabapentin has demonstrated benefits for treatment of alcohol use disorder, and therefore, like naltrexone, it could have a specific role for treating patients with chronic pain and unhealthy alcohol use. The results of the UH2 study were presented at the 2019 CPDD meeting.
What can we expect to learn from the UH3 components?
Both Dr. Palfai and Dr. Tsui are continuing onto the UH3 phase of their grants. Dr. Palfai’s UH3 study will be implemented as a between-groups study. The Motivation and Cognitive-Behavioral Management of Alcohol and Pain intervention will be compared to treatment as usual control condition. Forty-eight heavy drinking individuals receiving HIV care in the Boston area will be recruited into the study. Individuals that receive treatment will complete an in-person session followed by six videoconferencing intervention sessions. This intervention will follow the self-regulation framework, conscious personal management through thoughts, behaviors, and feelings, to account for hazardous/harmful drinking and pain. This study aims to obtain effect size estimates of intervention efficacy, with the potential of implementing this intervention as part of a larger clinical trial. Follow-up visits will be at three and six months. The primary outcomes of this study will include the number of drinks per week, number of heavy drinking episodes, alcohol related consequences, past week pain “interference” and “severity”, injection drug use and sexual risk behaviors, and patient distress due to HIV symptoms. Secondary outcomes will include Anti-Retroviral Therapy (ART) adherence, clinical care attendance to scheduled HIV clinic visits, viral suppression (HVL) at 6 months, frequency of days using illicit drugs, smoking quantity and frequency in the past 30 days, and depressive and anxiety symptoms.
Dr. Tsui is continuing to the UH3 portion of her grant, as well. The UH3 component will compare the effects of low-dose naltrexone or gabapentin to placebo on improving pain, inflammation, and measures of HIV control. This is a randomized, double-blinded, 3-arm study that will enroll 45 individuals with chronic pain, past year heavy alcohol use, and HIV. These participants will be treated with either gabapentin, low-dose naltrexone, or a placebo for eight weeks, and then will be assessed for an additional four weeks post-treatment. Follow-up visits will occur at one, four, eight, and twelve weeks post-enrollment with shorter check-in visits at weeks one, two, six, and seven. The primary outcome of the study will be change in past week pain severity and pain interference from baseline to week eight, as measured by the Brief Pain Inventory (BPI). Secondary outcomes include change in 1) pro-inflammatory biomarkers IL-6 and TNF-α, 2) cold pain tolerance using the cold-pressor test, 3) percentage of past month heavy drinking days, and 4) HIV control measures, including CD4 cell count and HIV viral load.
This UH3 study could illuminate a new treatment for HIV-positive patients with chronic pain and unhealthy alcohol use.
The results from these UH3 studies will inform directions for larger RCTs in both domestic and global contexts. Innovative behavioral and pharmacological interventions are needed to successfully target different aspects of chronic pain and alcohol use among PLWH.