Nearly all patients with NNRTI resistance could benefit from etravirine, UK analysis shows

The majority of patients with resistance to existing NNRTIs will benefit from treatment with etravirine (Intelence), a new, powerful NNRTI with a high barrier to resistance, according to a UK study published in the May 11^th edition of AIDS. The investigators believe that the “next generation of NNRTIs, including etravirine, will play an important future role in sequencing HIV-infected patients who have acquired NNRTI resistant virus.”

NNRTIs (non-nucleoside reverse transcriptase inhibitors) are recommended for use by people starting anti-HIV treatment for the first time. They have a powerful anti-HIV effect, which is long-lasting, and they cause few side-effects. But HIV can develop high-level cross-resistance to the two licensed NNRTIs (efavirenz, Sustiva and nevirapine, Viramune) after the emergence of a single NNRTI resistance mutation.

In the DUET clinical trials, etravirine was shown to be effective against HIV that was resistant to efavirenz and nevirapine. But there was a suggestion in the results of this study that the more NNRTI resistance mutations a patient had, the poorer their response to etravirine.

To see how useful etravirine would be in clinical practice, investigators at London’s Chelsea and Westminster Hospital conducted a retrospective analysis of the number and type of NNRTI resistance mutations in patients who had experienced an increase in their viral load to detectable levels during treatment with efavirenz or nevirapine.

Information on 743 patients was available for analysis. Researchers found that 39% of patients had one NNRTI resistance mutation; 32% had two NNRTI resistance mutations; 20% had three such mutations; and 7% had four NNRTI mutations; and 3% had five or more.

The prevalence of mutations conferring resistance to etravirine was as follows: 27%, zero mutations; 43%, one mutation; 20%, two mutations; and 11%, three or more mutations. The most commonly seen mutations conferring resistance to etravirine were V901, Y181C and G190A.

Investigators calculated that 89% who had NNRTI resistance after treatment with nevirapine would be susceptible to treatment with etravirine. Of the efavirenz treated patients with NNRTI resistance, it was calculated that 91% would benefit from treatment with etravirine.

“We predict the majority of our patients will have etravirine sensitivity after acquisition of NNRTI resistance following treatment with efavirenz or nevirapine”, conclude the investigators.