Treatment training manual

7. 7 ART interactions with methadone, buprenorphine, naloxone and heroin

There are several studies of interactions between HIV treatment (ART) and opioid agonist treatment.

METHADONE

  • All NNRTs affect levels of methadone, usually reducing them. With nevirapine or efavirenz, methadone levels in the blood can be 50% lower. Some people may need to increase the dose of methadone to overcome symptoms of withdrawal.
  • Darunavir boosted by cobicistat can increase levels of methadone, but boosting with  ritonavir can reduce them
  • A study of methadone and ritonavir in humans showed a decrease in methadone levels of 36% – but a previous test-tube study found a 30% increase.
  • The PI lopinavir/r (Kaletra, Aluvia) reduces levels of methadone by about 50%. Some people may need to increase the dose of methadone.
  • Although AZT is now rearely used, methadone doubles the levels of AZT in the body. Half the normal dose of AZT is recommended when used with methadone. Abacavir can reduce methadone levels.
  • Methadone levesl are not affected by unboosted integrase inhibitors or other NTRIs.

BUPRENORPHINE

  • Efavirenz (600 mg daily) reduced buprenorphine levels by 50% but this didn’t lead to increased reports of withdrawal symptoms.
  • Ritonavir-boosted atazanavir (100/300 mg daily) can significantly increase buprenophine levels. This can increase sedation, which can be addressed by reducing the dose of buprenophine.

naloxone

  • Naloxone (Narcan) is used to rapidly reduce or reverse high levels of opiods like heroin. Given soon after an overdose, naloxone can save lives.
  • There are no formal studies between HIV drugs and naloxone.
  • Based on the theoretical risk of interactions, ritonavir has the potential to reduce levels of naloxone. The concern is sufficient for a higher dose of naloxone to be used if the initial dose produces no clinical effect.
  • A similar reduction in naloxone levels is suggested with the boosted PI lopinavir/ritonvir (Kaletra, Aluvia).
  • There are no interactions with other boosted PI, with the PK booster cobicisat, or with any other currently approved HIV drugs.

HEROIN

  • Heroin (diamorphine) levels can be increased by efavirenz but are not significantly affected by other HIV drugs.

Lower methadone levels are not always followed by symptoms of withdrawal.

It can be hard to distinguish between ARV side effects and symptoms of withdrawal (eg nausea, vomiting).

  • Symptoms that develop within 2-3 days are probably from ARV toxicity.
  • Symptoms within hours are more likely to be from withdrawal.

Further reading

Liverpool University drug interaction factsheet.
Liverpool University: ART interactions with street and recreational drugs (PDF)

Last updated: 1 January 2023.