AEGiS-14IAC: GENOPHAR: an open prospective study of plasmatic drug measurements (PDM) associated with genotypic resistance testing (GRT) in patients failing antiretroviral therapy.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

GENOPHAR: an open prospective study of plasmatic drug measurements (PDM) associated with genotypic resistance testing (GRT) in patients failing antiretroviral therapy.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. WeOrB1264)

Bossi P, Peytavin G, Delaugerre C, David DJ, Ktorza N, Bonmarchand M, Mohand HA, Lamotte C, Cacace R, Simon A, Calvez V, Bricaire F, Costagliola D, Katlama C
Dpt of Infectious Diseases-Pitie-Salpetriere Hospital, Paris, France

BACKGROUND: To evaluate the benefit of PDM in association with GRT to optimize therapy in pts failing antiretroviral treatments (ART).

METHODS: In a single center, Pts with HIV-1 RNA>1000 cp/ml and stable ART in the last 3 mths were randomized in 2 groups: genotypic group (G) and geno-pharmacologic group (GP). Pts were evaluated monthly clinically, for safety parameters, for HIV-1 RNA, for CD4 cell counts and for PI and/or NNRTI peak and trough plasma levels until W 24. ART was selected by an expert committee according to GRT (G and GP) and PDM (GP) at W 4. Treatment could be modified at each visit according to toxicity, poor virological response and PDM. At W 12, results of PDM were available for G. Primary end-point study was the % of pts with HIV-1 RNA<200 cp/ml at W 12.

RESULTS: 137 pts were included at D0 (G, n=69 pts/GP, n=68 pts) and 127 were followed up to W 12. At baseline median values were: HIV-1 RNA (Log cp/ml: G=4.1; GP=4.0); CD4 cell count (/mm³; G=292; GP=294) and number of prior drugs (G=7; GP=8). Median number of resistance mutations was 8 in G (NRTI=3; NNRTI=1; PI=4) and 10 in GP (NRTI=4; NNRTI=2; PI=6). At W 8, ART was adjusted according to the PDM in 10/67 GP pts (15%). By ITT missing equal failure analysis at W 12, an HIV-1 RNA<200 cp/ml was achieved in 30/69 pts (43%) in the G group versus 28/68 pts (41%) in the GP group (ns). At W 24, HIV-1 RNA<200 cp/ml was achieved in 34/59 pts (58%) in the G group versus 40/61 pts (66%) in the GP group; median drop in HIV-1 RNA level was -1.3 log cp/ml [-3.1 to 1.4] and -1.6 log cp/ml [-2.9 to 0.7] respectively (ns). At W 24, median increase of CD4 cell count was 59/mm³ (G) and 60/mm³ (GP)(ns).

CONCLUSIONS: This study shows that combining GRT with the use of an expert committee to monitor individual subsequent therapy in pts with multiple resistance mutations was associated to a high antiviral efficacy with 62% of pts<200 cp/ml. The benefit of using PDM over 2 mths was not evidenced in this study.

Keywords: AEGIS, CD4 Lymphocyte Count, Prospective Studies, Antiretroviral Therapy, Highly Active, Drug Therapy, Combination, Mutation, Human, therapy, genetics, drug therapy

020707
WeOrB1264