Clinically validated mutation scores for HIV-1 resistance to fosamprenavir/ritonavir.
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.
Masquelier
B
B
Laboratoire de Virologie, CHU de Bordeaux and EA 2968, Université Victor Segalen, Bordeaux, France. bernard.masquelier@chu-bordeaux.fr
Assoumou
K L
KL
Descamps
D
D
Bocket
L
L
Cottalorda
J
J
Ruffault
A
A
Marcelin
A G
AG
Morand-Joubert
L
L
Tamalet
C
C
Charpentier
C
C
Peytavin
G
G
Antoun
Z
Z
Brun-Vézinet
F
F
Costagliola
D
D
D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics; D002219:Carbamates / Q000494:pharmacology / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D005260:Female; D005663:Furans; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D017320:HIV Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010755:Organophosphates / Q000494:pharmacology / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D019438:Ritonavir / Q000494:pharmacology / Q000627:therapeutic use*; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use*; D019562:Viral Load
D002219:Carbamates; D005663:Furans; D017320:HIV Protease Inhibitors; D010755:Organophosphates; D012367:RNA, Viral; D013449:Sulfonamides; D019438:Ritonavir; C426859:fosamprenavir