Naltrexone implants provide better HIV treatment outcomes for those with HIV and opioid addiction in Russia

A double-blind, placebo-controlled randomised trial conducted in Russia found that slow-release naltrexone implants resulted in better HIV treatment outcomes for people living with HIV and opioid dependence when compared to orally administered naltrexone. This research was carried out by Professor Evgeny Krupisky and colleagues at the First Pavlov State Medical University of St Petersburg, along with colleagues at the University of Pennsylvania, and was published in the April issue of The Lancet HIV.

Naltrexone is a drug that blocks the effects of opioids, with implants providing opioid-blocking effects for up to three months. However, in most countries the only licensed form of naltrexone is oral tablets or intramuscular injections; the oral dose only blocks the effects of opioids for 24 hours and needs to be taken daily while the injection has effects for up to a month. Currently, Russia is the only country where a regulatory agency has approved the use of a naltrexone implant.

At 48 weeks, people with naltrexone implants had completed more weeks of antiretroviral therapy (ART) and were more likely to be virally suppressed (66% vs 50%) than those taking oral naltrexone doses. The longer opioid effects were blocked, the more protection individuals received from missed ART doses and impulsive behaviours related to their addiction. The researchers concluded: “The higher proportion of relapse-free weeks and weeks in HIV treatment among participants with naltrexone implants than in participants taking oral naltrexone is the most likely contributor to better outcomes.”



Refers to the mouth, for example a medicine taken by mouth.


Something (such as a graft or device) implanted in a body tissue. In a context of prevention (such as contraception), the word refers to a device that will deliver an active agent slowly, over several months or years. This technique might be used one day to deliver antiretrovirals in the body for HIV prevention (PrEP) or treatment. 


The return of signs and symptoms of a disease after a patient has been free of those signs and symptoms. 


A pill or liquid which looks and tastes exactly like a real drug, but contains no active substance.

virological suppression

Halting of the function or replication of a virus. In HIV, optimal viral suppression is measured as the reduction of viral load (HIV RNA) to undetectable levels and is the goal of antiretroviral therapy.

Nearly 40% of all new HIV infections in eastern Europe are as a result of injecting drug use, with Russia accounting for three-quarters of all new infections in the region. Untreated opioid addiction is linked to poor ART adherence and outcomes in HIV-positive people. Methods used to manage opioid addiction elsewhere, such as opioid substitution therapy with methadone, are illegal in Russia. However, the naltrexone implant which provides slow-release naltrexone for up to three months is available in Russia. The authors wanted to investigate if this implant would offer superior outcomes in people living with HIV when compared to naltrexone taken orally.

The study

A 48-week double blind, placebo-controlled randomised trial was conducted with 200 HIV-positive men and women with a history of opioid addiction starting ART with viral loads greater than 1000 copies/ml in St Petersburg and surrounding areas. Stratification was carried out according to gender, viral load and CD4 cell counts and participants were then randomly allocated to either addiction treatment with a naltrexone implant and placebo oral naltrexone (implant group, 100 participants) or 50mg daily oral naltrexone and a placebo implant (oral group, 100 participants).

The primary outcome was viral suppression at 24 and 48 weeks (measured as less than 400 copies/ml). Secondary outcomes included adherence to ART, time to relapse and number of days relapsed, change in CD4 counts from baseline to week 48, number of appointments kept and so forth.

All participants were 18 years and older, met the criteria for opioid addiction but had gone through detox in the previous month, with no evidence of physical addiction at the time of enrolment. Participants were deemed ineligible if they displayed signs of physical dependence or withdrawal as naltrexone is not indicated in these cases. They had not received ART in the past year.

The implant and oral groups were well matched in terms of age (an average of 32 and 33 years), education (an average of eleven years), years since HIV diagnosis (eight and a half), years of opioid addiction (13) and CD4 count (220 cells/mm3 in the implant group and 249 cells/mm3 in the oral group at baseline). Males made up the majority of both groups (approximately 70%), and in both groups, most participants were unemployed (approximately 70%). There were high levels of hepatitis C co-infection (85% in the implant group, 88% in the oral group).

Participants began addiction and HIV treatment within three weeks of each other. Participants were also provided with addiction counselling that aimed to provide support, encourage adherence, help deal with cravings, avoid situations associated with drug use and general psychosocial support. Oral medication supplies were renewed at counselling sessions (unless the patient had relapsed); implants were reinserted every 12 weeks.


An intention to treat analysis was used for the final results; thus all participants who were initially randomised were analysed, regardless of loss to follow-up or relapse. At week 24, there was no statistically significant difference between the two groups in terms of viral load suppression. At week 48, 66% in the implant group and 50% in the oral group had viral loads less than 400 copies/ml (OR 1.94, CI: 1.06-3.58). Forty-six per cent of participants in the implant group completed 48 weeks of ART compared to 32% in the oral group; there were also more weeks of ART prescribed in the implant group than in the oral group (a median of 40 vs 21 weeks).

In terms of addiction treatment outcomes, those in the implant group had an average of 32 weeks of addiction treatment without relapse compared to 20 weeks for the oral group, while 32% in the implant group remained on addiction treatment to the end of the study, compared to 17% in the oral group. The odds of achieving a viral load below 400 copies/ml among those who completed addiction treatment were greater for the implant group than for the oral group (OR: 3.03, CI: 1.66-5.52). 

Regardless of group assignment, more participants who continued naltrexone treatment at both 24 and 48 weeks had viral loads less than 400 copies/ml than those who did not. The proportion of participants remaining in HIV and addiction treatment did not begin to differ widely until week 16, which likely explains there being no significant difference in viral load at week 24.

There were seven deaths; three in the implant group (one due to heart disease, one due to trauma and one due to AIDS) and four in the oral group (two due to overdoses, one due to pancreatic cancer and one due to AIDS). Deaths from overdose occurred 9-10 months after the last naltrexone dose.


This is the first study to evaluate the effects of a naltrexone implant on both HIV and opioid addiction outcomes for people with a history of opioid addiction. As Russia is the only country that currently offers these implants and has a high number of HIV-positive individuals with opioid addictions, these findings represent an important intervention for altering the course of opioid addiction and improving HIV outcomes.

Slow-release naltrexone implants resulted in better retention in addiction treatment. Those who were able to remain in addiction treatment for longer periods, with more relapse-free weeks, were also better at adhering to their HIV treatments. The findings of this study also have implications for other settings where implants may not yet be available but where there are high numbers of people with both HIV infection and opioid addiction.


Krupitsky E et al. Slow-release naltrexone implant versus oral naltrexone for improving treatment outcomes in people with HIV who are addicted to opioids: a double-blind, placebo-controlled, randomised trial. The Lancet HIV 6: 221-229, 2019. (Full text freely available).