Pharmacogenetics of Interaction between Efavirenz and Dolutegravir

Pharmacogenetics of Interaction between Efavirenz and Dolutegravir

For more than a decade, a pill containing the anti-HIV drug efavirenz plus two other anti-HIV drugs (nucleoside reverse transcriptase inhibitors, or “NRTIs”) has been a first-line treatment for adults living with HIV in many countries. Millions of adults worldwide are now taking efavirenz plus two NRTIs. When first-line treatment fails, patients often switch from efavirenz to an anti-HIV protease inhibitor plus two NRTIs. Recently the world is moving away from efavirenz and protease inhibitors, to instead use dolutegravir (a type of drug called an integrase inhibitor) plus two NRTIs, both as first-line and for treatment failure. This means that many people may soon switch from efavirenz- to dolutegravir-based treatment. Switching from efavirenz to dolutegravir appears to be safe and effective. When a person is taking efavirenz, some enzymes in their liver become more active. Because these enzymes break down other drugs, people taking efavirenz can have lower levels of some other drugs, and people with the highest efavirenz levels may have the lowest levels of the other drugs. A difference between people in a gene called CYP2B6 makes some people have higher efavirenz levels than other people. If a person taking efavirenz has the different CYP2B6, then other drugs in that person's body may be even lower. This proposal is to see if people with the different CYP2B6, and who were taking efavirenz, had lower dolutegravir levels in their blood compared to people without the different CYP2B6. This may be important for some people during the days after switching from efavirenz to dolutegravir.

[{ "PostingID": 19695, "Title": "VIIV-ING114005", "Description": "A Phase 1, Open Label, Single Sequence, Three Period Study to Evaluate the Single Dose Pharmacokinetics of GSK1349572 100mg versus 50mg and the Effect of Efavirenz 600mg Once Daily on the Pharmacokinetics, Safety and Tolerability of GSK1349572 50mg Once Daily in Healthy Adult Subjects (ING114005)" }]

David W Haas, MD, Edward P Acosta, PharmD, Implications of Efavirenz Pharmacogenetics when Switching from Efavirenz- to Dolutegravir-containing Antiretroviral Regimens, Clinical Infectious Diseases, , ciaa975,

https://doi.org/10.1093/cid/ciaa975