• Efficacy of Emtricitabine (FTC) in HIV-Infected Patients With High Pre-Treatment Viral Load (Poster 546)
  Authored by I. Sanne, M. Saag, A. Shaw, E. Mondou, J. Hinkle, J.B. Quinn, F. Rousseau for the FTC-301 and FTC-302 Study Teams

The purpose of this paper was to look at the efficacy of FTC (emtricitabine, Emtriva) in patients with viral loads higher than 100,000 copies/mL. The logic of doing this is two-fold. First, patients with high baseline viral loads have more difficulty achieving long lasting viral control, at least in some studies. Second, in some studies, differences in drug potency are more prominent in the high viral load subgroup, and therefore easier to spot.

Examples of this go all the way back to the dose-finding licensing study of nelfinavir (NFV, Viracept), called AG 511. In that study, the two doses of nelfinavir, 500 mg three times a day and 750 mg three times a day, were fairly similar in the early analyses. It was the differences in those who started with high viral loads and the long-term results that made it clear that the 500-mg dose was inadequate. This difference, limited to the high viral load subgroup, cropped up in a pivotal early study of Trizivir (abacavir [ABC, Ziagen] + 3TC [lamivudine, Epivir] + AZT [zidovudine, Retrovir]), foreshadowing the results of ACTG 5095.

For this paper, the authors combined data from two different studies that compared FTC with a comparison agent, combined with a backbone of another nucleoside and a nonnucleoside. Virologic failure was defined as never achieving a viral load less than 50 copies/mL or two consecutive viral loads over 50 copies/mL after achieving success. Here are the trials and the designs:

• FTC 301: FTC/ddI (didanosine, Videx)/efavirenz (EFV, Sustiva) versus d4T (stavudine, Zerit)/ddI/efavirenz

• FTC 302: FTC/d4T/efavirenz or nevirapine (NVP, Viramune) versus 3TC/d4T/efavirenz or nevirapine

In FTC 302, the choice of either efavirenz or nevirapine was determined by viral load: all patients with a viral load greater than 100,000 copies/mL received efavirenz, the remainder received nevirapine.

The authors report that the probability of virologic failure among persons with a viral load of more than 100,000 copies/mL at 48 weeks to be:

• 8.1 percent for the FTC regimens

• 21.1 percent in the combined comparison arms

In the less than 100,000 copies/mL groups the probability is:

• 8.3 percent for the FTC regimens

• 12.2 for the combined comparison arms

The poster concludes that "FTC is a potent once-daily NRTI that provided significant efficacy within a HAART regimen in treatment-naive HIV-infected patients with viral load more than 100,000 copies/mL as well as less than 100,000 copies/mL." I agree with the conclusion. FTC is potent and well tolerated, based on this and other studies presented at this meeting and elsewhere. There have been no hints that the regimen is compromised in patients with high viral loads.

Did this paper add to that conclusion? I have some problems with the poster and the analysis. It is difficult to combine data from differing studies because of obvious differences in the regimens, as well as subtle differences in the time, locale and conduct. This can be dealt with to some degree with sophisticated statistical analysis, but if that was done, it was not discussed in this paper.

Sometimes, the parts themselves stand alone without any help from a combined analysis. FTC, like 3TC, can be used as part of a variety of potent regimens regardless of viral load.