AEGiS-15IAC: GW433908 (908)/ritonavir (r): 48 week results in PI-experienced subjects: A retrospective analysis of virological response based on baseline genotype and phenotype.

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

GW433908 (908)/ritonavir®: 48 week results in PI-experienced subjects: A retrospective analysis of virological response based on baseline genotype and phenotype.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. MoOrB1055)

R C Elston¹, P Yates¹, M Tisdale¹, N Richards², S White², E DeJesus³
GlaxoSmithKline, Stevenage, United Kingdom

BACKGROUND: 908, an HIV PI, recently approved in US(Lexiva™) and under review in EU(proposed Telzir™). CONTEXT (APV30003) was a 48 Wk Phase III study which included comparison of 908/r (700mg/100mg BID) with Lopinavir/r (400mg/100mg BID). This analysis describes the 48 Wk efficacy results and the correlation of baseline resistance with virological response.

METHODS: Subjects had to have experienced virologic failure (VF) to 1-2 prior PI-containing regimens, had to be able to construct an active backbone of two NRTIs (NtRTI) based on a VGI resistance test (v 4.0 or 5.0). NNRTI use was not permitted. Proportion efficacy endpoints were based on ITT(E) RD=F analysis. Baseline genotyping and phenotyping (Phenosense Assay) was performed. Only subjects discontinuing therapy for VF were included in the resistance analysis.

RESULTS: Baseline viral load, CD4 levels, PI experience and PRO mutations were similar between arms, but NRTI experience and RT mutations were higher in the 908/r arm. The proportion of subjects with sustained virological suppression at Wk 48 was:<400copies/mL, 908/r 62/107 (58%), LPV/r 63/103 (61%);<50copies/mL 908/r 49/107 (46%), LPV/r 52/103 (50%). The proportion of subjects that were VFs was: 908/r 29/107 (27%), LPV/r 28/107 (27%). Major protease mutations L90M (63/210,30%), M46I/L (48/210, 23%) and D30N (45/210, 21%) were seen most commonly at baseline. Similar virological response rates were observed with these mutations between the 908/r and LPV/r treatment groups respectively: L90M (16/31, 52% vs 17/28, 61%), M46I/L (11/22, 50% vs 12/24, 50%) and D30N (21/22, 95% vs 17/18, 94%). VF in the presence of L90M or M46I was associated with resistance to the randomised PI, (L90M - 908/r 12/15 non responders [NR] vs 3/16 responders [R]; LPV/r 10/11 [NR] vs 3/17 [R])(M46I/L - 908/r 10/11[NR] vs 3/11[R], LPV/r 12/12 [NR] vs 6/12 [R]).

CONCLUSION: 908/r BID and LPV/r BID are effective PIs in subjects failing one or two prior PI-containing regimens.

Keywords: AEGIS, Ritonavir, Phosphoric Acid Esters, Genotype, Phenotype, HIV Protease Inhibitors, Pyrimidinones, Sulfonamides, HIV Protease, Viral Load, HIV Infections, Anti-HIV Agents, HIV, Glass Ionomer Cements, fosamprenavir, lopinavir, BaseLine, virology, genetics

040711
MoOrB1055