• The NEAT Study: GW433908 Efficacy and Safety in ART-Naive Subjects: Final 48-Week Analysis (Oral 177)
  Authored by J. Nadler, A. Rodriguez-French, J. Millard, P. Wannamaker
  View the original abstract

The 48-week results of the NEAT Study were presented by Jeff Nadler (click here to see our coverage at 24 weeks). In the NEAT Study, 251 treatment-naive subjects with plasma RNA >5000 copies/ml were randomized 2:1 to receive GW433908 (908) the calcium phosphate ester pro-drug of amprenavir (APV, Agenerase) 1,400 mg BID or nelfinavir (NFV, Viracept) 1,200 mg BID, with all subjects receiving standard doses of abacavir (ABC, Ziagen) and 3TC (lamivudine, Epivir) BID.

The population enrolled was quite diverse: 44 percent Hispanic and 32 percent African-American with similar baseline CD4 and RNA levels (median RNA = 4.82 log and median CD4 = 212). Overall, 30 percent of the 908 arm prematurely discontinued the study versus 46 percent of the NFV arm. The median increase in CD4 from baseline was 201 in the 908 arm versus 216 in the NFV arm.

The percentage below 400 and 50 copies of HIV RNA at 48 weeks was higher in the 908 arm (66 percent and 58 percent) than in the NFV arm (48 percent and 42 percent).

The median increase in LDL at 48 weeks was 33 in both the 908 arm and NFV arms while the triglycerides increased 1 mg/dL in the 908 arm versus 46 mg/dL in the NFV arm.

The study demonstrated the greater virologic efficacy of 908 versus NFV. The high withdrawal rate is of concern and one has to wonder if many of the study subjects enrolled were simply not really ready to start treatment. A 58 percent success at 48 weeks is fair but well below the results seen in several efavirenz (EFV, Sustiva)-based trials. However, it was pointed out to me that the overall HIV disease status in this study was quite advanced with a high proportion of patients with CD4 < 50 or viral loads > 100,000. 908 was equally active across all of the HIV RNA strata in contrast to NFV, which was less effective in the higher RNA strata. These results position 908 to be considered as a first-line protease inhibitor (PI), though data on resistance profiles and a direct comparison to atazanavir (Zrivada) would be helpful in sorting that out.