Analysis of possible predictors of response to abacavir (ABC) in antiretroviral-experienced adults; comparison of viral genotype, viral phenotype, and patient treatment history
Originally Published on May 12, 1999
Lanier R, Ait-Khaled M, Madison S, et al.
6th Conference on Retroviruses and Opportunistic Infections. 31 Jan-4 Feb, 1999, Chicago, IL. Abstract 134.
ABSTRACT:
Resistance to ABC is selected relatively slowly in vitro, requiring multiple mutations to achieve an 8-fold increase in IC50 over wild-type virus. Sequential in vitro passage of a laboratory strain (HIVIIIB) selected for mutations at positions 65(R), 74(V), 115(F) and 184(V). These mutations are also seen in vivo with 184V being most frequent. Therapy-experienced adults added ABC to background therapy in four clinical trials (CNA2003, 3001, 3002 and 3009). The length of prior nucleoside reverse transcriptase inhibitor (NRTI) therapy ranged from 3 months to many years. Baseline (BL) viral genotype, resistance phenotype and viral RNA (vRNA) response at 12-24 weeks (trial-dependent) after addition of ABC were available for 89 patients.
Baseline viral genotype, median phenotype (x fold) and vRNA response.
Genotype
<400 c/ml
0.5log10 ¯
or <400 c/cl
BL vRNA
vRNA change
wild-type (n=11)
55% (1x)
82% (1x)
4.65 log10
-1.66 log10
184V only (n=28)
68% (2x)
89% (2x)
3.67 log10
-0.76 log10
1-2 Muts (n=51)
55% (2x)
76% (2x)
3.94 log10
-0.74 log10
„3 Muts n=27
7% (5x)
22% (4x)
4.42 log10
-0.04 log10
The number of baseline mutations associated with NRTI resistance generally corresponded with phenotypic resistance, duration of prior therapy, BL vRNA level and vRNA response following addition of ABC. Mutiple baseline RT mutations corresponded with phenotypic resistance and poor viral response. The antiviral efficacy of ABC was similar when baseline virus was wild-type or had 1-2 mutations associated with NRTI resistance. These data support a role for ABC in therapy experienced patients.
