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© Research
Publication : The Journal of antimicrobial chemotherapy

Clinically validated mutation scores for HIV-1 resistance to fosamprenavir/ritonavir

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in The Journal of antimicrobial chemotherapy - 04 Apr 2008

Masquelier B, Assoumou KL, Descamps D, Bocket L, Cottalorda J, Ruffault A, Marcelin AG, Morand-Joubert L, Tamalet C, Charpentier C, Peytavin G, Antoun Z, Brun-Vézinet F, Costagliola D,

Link to Pubmed [PMID] – 18390885

J. Antimicrob. Chemother. 2008 Jun;61(6):1362-8

BACKGROUND: We developed clinically relevant genotypic scores for resistance to fosamprenavir/ritonavir in HIV-1 protease inhibitor (PI)-experienced patients.

METHODS: PI-experienced patients with virological failure receiving fosamprenavir/ritonavir as the sole PI for at least 3 months and with detectable fosamprenavir plasma levels were included. The impact of baseline protease mutations on virological response (VR, i.e. decrease in plasma HIV-1 RNA between baseline and month 3) was analysed using the Mann-Whitney test. Mutations with prevalence >10% and P value <0.10 were retained. The Jonckheere-Terpstra test was used to select the combination of mutations most strongly associated with VR. The association between score and VR was assessed by multivariate backward regression.

RESULTS: In the 73 patients included, the median baseline HIV-1 RNA was 4.6 log(10) copies/mL (range: 2.7-6.9) and the mean decrease at month 3 was -1.07 +/- 1.40 log(10) copies/mL. Ninety per cent of the patients were infected by HIV-1 subtype B variants. Two fosamprenavir/ritonavir mutation scores were constructed: score A (L10F/I/V + L33F + M36I + I54L/M/V/A/T/S + I62V + V82A/F/C/G + I84V + L90M) was based only on mutations associated with a worse VR, whereas score B (L10FIV + L33F + M36I + I54L/M/V/A/T/S + A71V – V77I – N88S + L90M) also took into account favourable mutations. Both scores were independent predictors of VR, however, co-administration of tenofovir was associated with a worse VR and the presence of the N88S protease mutation and co-administration of enfuvirtide with a better VR.

CONCLUSIONS: These clinically validated mutation scores should be of interest for the clinical management of PI-experienced patients. The fosamprenavir/ritonavir score A was introduced in the 2006 ANRS algorithm along with isolated mutations I50V and V32I + I47V.

http://www.ncbi.nlm.nih.gov/pubmed/18390885