Back HIV Treatment Experimental HIV Drugs IAS 2011: New NNRTI Lersivirine Looks Good in Phase 2 Study

IAS 2011: New NNRTI Lersivirine Looks Good in Phase 2 Study


Lersivirine, an investigational non-nucleoside reverse transcriptase inhibitor (NNRTI), lowered HIV viral load about as well as efavirenz (Sustiva) for people starting antiretroviral therapy for the first time, researchers reported at the 6th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2011) this week in Rome.

[Produced in collaboration with]

Lersivirine (formerly known as UK-453,061), being developed by ViiV Healthcare, has a unique binding pattern to HIV's reverse transcriptase enzyme, enabling it to remain active against HIV with certain NNRTI resistance mutations (including Y181 changes).

Anton Pozniak from Chelsea and Westminster Hospital in London reported findings from a Phase 2b trial (Study A5271015) comparing lersivirine vs efavirenz for first-line therapy.

This multinational study included 195 treatment-naive participants with no reverse transcriptase resistance mutations evident at baseline. About three-quarters were men, about 60% were white (though this varied across sites) and the average age was 36 years. The median baseline CD4 cell count was approximately 320 cells/mm3.

Participants were stratified according to viral load (above or below 10,000 copies/mL) and geographic region. About one-third lived in South Africa, with the rest in Europe, North and South America, and Australia; a corresponding proportion had HIV Clade C, whilst most of the rest had Clade B.

Participants were randomly assigned to received 500 mg lersivirine, 750 mg lersivirne, or efavirenz once-daily, in combination with tenofovir/emtricitabine (the drugs in Truvada).


  • In an overall intent-to-treat analysis at 48 weeks, 79% of participants in both lersivirine dose groups achieved viral load below 50 copies/mL, compared with 89% of those taking efavirenz, not a statistically significant difference.
  • CD4 cell gains were good in all arms at about 100 cells/mm3 per month.
  • Both the 500 mg and 750 mg doses of lersivirine did not work as well as efavirenz for people with high viral load (75% vs 62% vs 82%, respectively).
  • This was also the case among South Africans compared with patients in higher-income countries (72% vs 68% vs 83%, respectively).
  • Further analysis found that the viral load difference was significant only among South Africans.
  • 12 participants in each lersivirine arms and 9 in the efavirenz arm discontinued treatment early.
  • Lersivirne was somewhat better tolerated than efavirenz overall.
  • Serious adverse events and discontinuations for this reason were uncommon and frequency was similar across arms.
  • People taking lersivirine experienced fewer neuropsychaitric side effects, as expected, but had more nausea (usually mild).
  • Looking at the secondary endpoint of changes in blood lipids, participants taking lersivirine had:
    • smaller increases in total cholesterol;
    • smaller increases in triglycerides;
    • larger increase in HDL "good" cholesterol;
  • However, the ratio of total-to-HDL cholesterol remained the same in all arms.
  • Overall, Pozniak described lersivirine as "lipid neutral."
  • Among participants who experienced virological failure, emergence of resistance mutations occurred more often in the 500 mg lersivirine arm than the higher-dose lersivirine or efavirenz groups.
  • The K103N mutation was not seen in anyone taking lersivirine and one patient taking efavirenz.

In discussing these findings, Pozniak explained that the apparently slightly worse virological suppression with lersivirine was driven by people with high viral load in South Africa, suggesting this may be attributable to poor adherence. Although lersivirine looks promising, he stressed that this analysis was not designed to determine superiority or non-inferiority, and Phase 3 studies are planned.



P Vernazza, C Wang, A Pozniak, et al. Efficacy and safety of lersivirine (UK­453,061) vs efavirenz in antiretroviral treatment­naive HIV­1-infected patients: week 48 primary analysis results from an ongoing, multicentre, randomised, double-blind, phase IIb trial (study  A5271015). 6th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2011). Rome, July 17-20, 2011. AbstractTUAB0101.