Naltrexone implant helps HIV patients with opioid dependence prevent relapse

The study was conducted in Russia where oral, extended-release injectable, and implantable naltrexone products are approved, but agonist or partial agonist maintenance using medications, such as methadone or buprenorphine, are against the law. Agonists remain controversial in some cultural settings because they activate the same neurological receptors as opioids, and some critics view the approach as exchanging one drug addiction for another. Naltrexone has been approved by the U.S. Food and Drug Administration (FDA) since the 1970s, however the only commercially available forms are the 50 mg tablet and an extended-release injectable product that blocks opioid effects for a month.

"The findings have implications for treatment of opioid dependence among patients that do not want agonist maintenance or who live in places where options are more limited," said senior author George E. Woody, MD, an emeritus professor in the department of Psychiatry at the Perelman School of Medicine at the University of Pennsylvania. "Further development and formal approval of these implants in a wider range of cultural settings has the potential to provide an effective and meaningful HIV and opioid treatment option for these patients."

In the phase 3, double-blind, double-dummy trial, researchers from Penn, the First Pavlov State Medical University and the VM Bekhterev National Medical Research Centre for Psychiatry and Neurology in Saint Petersburg, Russia, enrolled 200 people seeking treatment for HIV and opioid dependence, and assessed HIV and addiction treatment outcomes over the next 12 months. All participants had the study explained, provided informed consent, were not on HIV treatment or had not been on it for the past year, and had viral loads over 1,000 copies per mL. The researchers randomly assigned participants to receive the naltrexone implant every 12 weeks along with daily placebo oral naltrexone (100 people), or oral naltrexone 50 mg/day along with a placebo implant (100 people). All were offered biweekly drug counseling and treated with antiretroviral therapies.

Results of the study showed that the implant was associated with more HIV infected patients maintaining their ART regimen and lowering viral loads compared to the oral drug. At the end of the study, 46 people in the implant group remained on ART compared to 32 in the oral drug group, and 66 people in the implant group had viral loads less than 400 copies per mL compared to 50 in the oral group. The remainder of patients dropped out or relapsed and seven died from various causes including heart disease, trauma, overdose, cancer and AIDS. The implant group also remained in addiction treatment without relapsing for a longer period of time: 32 weeks vs. 20 weeks. The authors said that patients in the implant group likely had better outcomes because they had longer periods of remission, which in turn allowed them to focus more on HIV treatment than purchasing and using opioids.

"While we only looked at an opioid addicted HIV population in Russia, these results suggest that naltrexone implants could be helpful to patients in the U.S. and elsewhere that do not want agonist maintenance treatment or who live in settings where these treatments are difficult to access or unavailable," Woody said. "However, that will largely depend on the results of commercial development and approval of these implants."

Additional Penn co-authors of the study include Daniel Langleben, Sabrina Poole, and Robert Gross.

The work was supported by the National Institute on Drug Abuse (R01 DA026336, K05 DA17009, U10 DA013043, UG1 DA013034), the Penn Center for AIDS Research (P30 AI 045008), and the Penn Mental Health AIDS Research Center (P30 MH 097488).

Editor's Note: Co-author Evgeny Krupitsky, MD, was a consultant for Prodetoxon in 2017. Woody and Krupitsky are consultants on an NIDA grant to BICX102 for development of a similarly-acting implant in the U.S.