September 16, 2003
This has meant that we need to have more and more drug interaction studies done as we use new drugs and new combinations. Originally, it seemed reasonable to focus on drugs expected to have a possible effect or interactions, but those assumptions can be wrong.
Emtricitabine (originally known as FTC and sold under the brand name Emtriva, from Gilead Sciences) is a newly licensed once-daily nucleoside analog which has many similarities to 3TC (lamivudine, Epivir). Although it was approved by the FDA this spring, work on drug-drug interactions is continuing.
Two studies presented at ICAAC were important even though they showed no interaction. In part, they are important because they were carefully and promptly done, even though one might have guessed that they would not have any interaction.
One study by Gilead Sciences showed that FTC and 3TC do not change each others levels to any meaningful extent. Thirty healthy, HIV-negative volunteers participated in the study. There is a 13 percent change in the total exposure to AZT (zidovudine, Retovir), but this is not going to have any clinical effect. FTC has been combined with AZT in some studies and in many patients. This combination makes sense based on the safety and efficacy of the combination of AZT and 3TC (the ingredients of the popular medication Combivir). There is also a beneficial interaction between the resistance pathways of the two drugs. M184V, the mutation that confers resistance to 3TC and FTC, reverses the effects of some AZT and d4T (stavudine, Zerit) resistance mutations.
In the second study by Gilead investigators, FTC was combined with tenofovir DF (TDF, Viread). Nineteen HIV-negative volunteers participated in this 21-day study. The plasma levels of tenofovir and of FTC were completely unchanged when the volunteers took the drugs by themselves compared to when they were taken together.
This study was probably more significant. Both tenofovir and FTC are once-a-day drugs that have few side effects and work well together as a backbone for NNRTIs or protease inhibitors. But the obvious fact is that they are both made by Gilead, who is actively developing a combination tablet. This makes good clinical sense (and it seems, good business sense) since one daily tablet would provide the backbone for a once-daily regimen.
Efavirenz (EFV, Sustiva), boosted atazanavir (ATV, Reyataz) or boosted saquinavir (SQV, Invirase or Fortovase) are approved for once-daily use, and good data suggest that nevirapine (NVP, Viramune) can be used once daily. The forthcoming protease inhibitor fosamprenavir (908, when boosted) and lopinavir/ritonavir (LPV/r, Kaletra) have been investigated as once-daily options. Moreover, abacavir (ABC, Ziagen) and 3TC are being investigated as a single tablet with once-daily dosing.
These options may soon make for complex choices. But they mean that a potent regimen may soon mean two or three pills taken once a day! It was not that long ago that successful treatment meant 12 to 18 pills two or three times daily with complicated timing and food restrictions. Good news indeed.