[5] PHASE II 24-WEEK DATA FROM STUDY AI424-008: COMPARATIVE RESULTS OF BMS-232632, STAVUDINE, LAMUVIDINE AS HAART FOR TREATMENT-NAÏVE HIV-INFECTED PATIENTS

1st International AIDS Society Conference on HIV Pathogenesis and Treatment

Buenos Aires, Argentina - July 8-11, 2001

[TITLE:] PHASE II 24-WEEK DATA FROM STUDY AI424-008: COMPARATIVE RESULTS OF BMS-232632, STAVUDINE, LAMUVIDINE AS HAART FOR TREATMENT-NAÏVE HIV-INFECTED PATIENTS

[AUTHOR(S):] Cahn P, Percival L, Phanuphak P, Sanne I, Kelleher T, Giordano M
Fundacion Huesped, Buenos Aires, Argentina

IAS Conf HIV Pathog Treat 2001 Jul 8-11;1st: Abstract No. 5

[ABSTRACT:] Objective: Compare efficacy of BMS-232632 (BMS), a potent HIV protease inhibitor (PI), with that of nelfinavir (NFV), combined with d4T & 3TC, for ARV-naïve HIV-infected patients.

Methods: 464 patients with HIV RNA >2000 c/mL and CD4>100 cells/mm³ (>75 if C HIV disease not present) were randomized to BMS 400 or 600 mg QD (blinded by dose; n=373) or open-label NFV, 1250 BID mg (n=91), with d4T and 3TC.

Results: After 32 weeks, BMS and NFV regimens appear to be well tolerated. 13 patients discontinued treatment due to adverse events (AEs) or serious AEs. None of these SAE’s were drug-related. Commonly reported AEs were diarrhea (54% of NFV patients, 13% of BMS patients) and jaundice (17% of BMS patients). Other AEs were headache (20% NFV and 22% BMS), infection (43% NFV and 44% BMS), nausea (16% NFV and 10% BMS), peripheral neurologic symptoms (14% NFV and 16% BMS), asthenia (14% NFV and 12% BMS), abdominal pain (14% NFV and 9% BMS), and rash (12% NFV and 12% BMS). Dose-proportional hyperbilirubinemia grades 3–4 without hepatic transaminitis was reported in BMS patients (42%). Grade 3–4 ALT and AST elevations were more frequent in NFV patients than in BMS patients (ALT, 8% vs 4%; AST, 4% vs 3%). Little median change in lipid concentrations were observed in BMS patients, while much larger changes were observed in NFV patients:

	TC (mg/dL)	LDL-C (mg/dL)	TG (mg/dL)
	Baseline wk 24	Baseline wk 16	Baseline wk 16
BMS	168 +2	97 –4	99 –3
NFV	167 +28	94 +27	99 +30

Treatment-emergent hypercholesterolemia developed in 30 (9%) of 347 BMS patients and 33 (39%) of 85 NFV patients.

Conclusions: BMS-232632 is safe and well-tolerated and associated with substantially lower concentrations in the serum lipids known to increase cardiovascular risk. The unblinded 24-week results, including efficacy (proportion <50 c/mL and <400 c/mL, and CD4), tolerability and safety will be reported.

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