There are several studies of interactions between ARVs and methadone.

• Efavirenz and nevirapine reduce levels of methadone. Methadone levels in the blood can be up to 60% lower. Some people may need to increase the dose of methadone to overcome symptoms of withdrawal.
• A study of methadone and ritonavir in humans showed a decrease in methadone levels of 36%. This is interesting because a previous study in the test tube found a 30% increase.
• PIs nelfinavir and Kaletra reduced levels of methadone. Some people may need to increase the dose of methadone.
• Methadone doubles the levels of AZT in the body. Half the normal dose of AZT is recommended when used with methadone.
• In contrast, methadone appears to decrease levels of d4T and ddI. There are no guidelines for dose adjustment.

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 that develop after 6 days are more likely to be from withdrawal.

Further reading

An overview of drug interactions between methadone, buprenorphine and HIV medications was published in the i-Base publication ARV4IDUs.