Background: GW433908 (908) is an investigational protease inhibitor (PI) offering convenient dosing and a distinct resistance profile. This open-label, randomized study in ART naïve subjects compared the efficacy and safety of 908 to nelfinavir (NFV) over 48 wks.

Methods: A total 251 (249 treated) subjects with plasma HIV-1 RNA (vRNA) ≥ 5000 c/mL were randomized 2:1 to 908 1,400mg BID or NFV 1,250mg BID. All subjects received ABC and 3TC BID and were stratified at entry based on vRNA.

Results: This diverse population (24% Caucasion, 32% African American, and 44% Hispanic) had baseline (BL) attributes that were similar between arms: median HIV-1 RNA (range) was 4.82 (1.7–7.4) and 4.85 (2.5–6.6) and CD4⁺ were 211 (2–1136) and 213 (2–985) for 908 and NFV, respectively. Approximately 50% of subjects had vRNA >100,000 c/mL and CD4⁺ cells < 200 cells/mm³ and 18% of subjects had CD4⁺ < 50 cells/mm³. Overall, 30% (908) and 46% (NFV) of subjects prematurely discontinued the study. The median CD4⁺ change from BL was 201 and 216 cells/mm³ on 908 and NFV, respectively.

While some elevations in lipid values were observed in both groups, the mean values at wk 48 remained within the optimal/near optimal ranges per NCEP guidelines, except triglycerides for NFV BID at wk 48. The overall incidence of drug related Grade 2–4 adverse events (AEs) was comparable; diarrhea was the only significantly different AE being higher on NFV (18% vs 5%, p = 0.002).

Conclusions: In this study, 48 wk ITT (M = F) results demonstrate evidence of greater efficacy with 908 over NFV in proportions of patients with vRNA < 400 and < 50 c/ml. In this relatively advanced and diverse patient population, these results, together with a generally well tolerated safety profile, demonstrate that 908 is a promising new addition to current therapy options.

 

Data at 48 weeks (ITT M = F)		908 BID n = 166		NFV BID n = 83		Stratified D (95% CI)
vRNA	vRNA % < 400 c/mL	66%		48%		17% (5%, 30%)
	vRNA % < 400 c/mL by BL vRNA	£ 100,000 65%	> 100,000 67%	£ 100,000 59%	> 100,000 35%
	vRNA % < 50 c/mL	58%		42%		16% (3%, 28%)
	vRNA % < 50 c/mL by BL vRNA	£ 100,000 56%	> 100,000 60%	£ 100,000 57%	> 100,000 24%
	AAUCMB (log10copies/ml)	-2.26		-2.24		-0.015 (-0.247, 0.217)

 

		908 BID		NCEP Guidelines	NFV BID
	Mean values (mg/dL)	BL	Wk 48	Optimal/ Near Optimal range	BL	Wk 48
Lipids	Total cholesterol	152	197	< 200 mg/dL	153	202
	LDL Cholesterol	86	119	< 130 mg/dL	89	122
	HDL Cholesterol	37	49	> 40 mg/dL	36	44
	Triglycerides	151	152	< 150 mg/dL	154	200