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.”
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.
Results
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.
Conclusion
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.
