The End of Efavirenz?

Throughout the past decade, Efavirenz has been the backbone of ART regimens for people in the United States* living with HIV. Efavirenz is available in a fixed-dose combination pill with TDF and FTC (brand name “Atripla”). However, there has been a shift in the last two years away from the use of Efavirenz. The concern with Efavirenz is its CNS toxicity (vivid dreams, depression, and especially suicidality). So what drugs are replacing Efavirenz?

Based on the DHHS guidelines and several important clinical trials (“SINGLE” and “FLAMINGO“), the answer is the integrase inhibitors. Among the integrase inhibitors, dolutegravir based regimens are preferred over raltegravir (which must be taken twice daily) or elvitegravir. Incidentally, sales of dolutegravir are expected to climb to $6.1 billion by 2020.

If HIV patients are not adherent to integrase-based ART regimens, resistance can develop, however. Darunavir (a protease inhibitor, or PI) is an attractive option in such patients because of its high genetic barrier to resistance, when compared to the integrase inhibitors. For this reason, the PIs are here to stay. As for the nucleoside inhibitors, TDF, ABC, and FTC are the most commonly used ones. But with ongoing concerns about nephrotoxicity and bone mineral density, TDF may soon be replaced by a drug called TAF.

Although some of this seems to be driven by “pharmacoeconomics” and an unacceptably high percentage of HIV patients in the United States are not in care, a bit of perspective is in order. I was recently reading a copy of the 1992-93 HIV recommendations that my mother gave me (she was working as an HIV nurse in Detroit at the time). 22 years ago, we had only three HIV drugs available: AZT, ddI, and ddC. All three were very toxic and HIV patients progressed through them to AIDS and often died. But in 2015, HIV is no longer a death sentence, as long as patients have access to the expensive new drugs like dolutegravir.

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*In poor areas of the world, integrase inhibitors are inaccessible due to high cost

2 thoughts on “The End of Efavirenz?

  1. Nice post.

    I don’t follow this area as closely as I once did, but there are some good works abroad and I’m not sure the statement “What happens in America is completely different from Sub-Saharan Africa and other poor areas of the world, where the new drugs are inaccessible” is accurate or fair to the companies involved.

    Viv Healthcare has signed a license with the Medicines Patent pool covering pediatric use in countries where 99.3% of children living with HIV in the developing world reside. The adult licence territory covers at least 73 countries with 89% of people living with HIV.

    Gilead Sciences has signed a license with the Medicines Patent pool covering tenofovir alafenamide, tenofovir disoproxil fumarate, emtricitabine, cobicistat, elvitegravir and the Quad [a combination of TDF, FTC, COBI, and EVG]. These licenses cover about 90% of people living with HIV in the low and middle income countries.

    These are not 1980’s nucleosides, but drugs that have been approved in the last 2 years, or in some cases, have not yet achieved regulatory approval in developed countries.

    John A Tucker

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