Changes in darunavir/r resistance score after previous failure to tipranavir/r in HIV-1-infected multidrug-resistant patients.
OBJECTIVE
To evaluate changes in resistance to tipranavir/r (TPV/r) and darunavir/r (DRV/r) in patients who had failed a TPV/r-including regimen.


METHODS
HIV genotypes obtained both at baseline and at tipranavir/r failure (TPVF) were analyzed in 47 HIV-infected patients failing a TPV/r-including regimen. Genotypes were evaluated through the Stanford mutation score: patients were ranked for TPV/r and DRV/r resistance as susceptible (class 1), potential low-level (class 2), low-level (class 3), intermediate-level (class 4), and high-level resistance (class 5). Values are expressed as median (interquartile range) or as frequency (%).


RESULTS
Forty-seven patients were eligible. At baseline (tipranavir initiation), the scoring for TPV/r was: class 3 = 4 (8.5%); class 4 = 31 (66%); and class 5 = 12 (25.5%). Corresponding scores for DRV/r were: class 2 = 1 (2%), class 3 = 12 (25.5%), class 4 = 32 (68%), and class 5 = 2 (4.5%). At TPVF, a shift toward a higher TPV/r scoring class was seen in 16 (34.1%) patients (P = 0.001), whereas a shift toward a higher DRV/r scoring class was observed in 9 (19.2%) patients (P = 0.2381). After TPVF, 25/47 patients (53%) were treated with a DRV/r-containing regimen. After 24 weeks (on-treatment analysis), the median HIV RNA decrease was 3.04 (2.13-3.45) log10 copies per milliliter in DRV/r group versus -0.04 (-0.44; 0.50) log10 copies per milliliter in patients not treated with a DRV/r-containing regimen (P < 0.0001); CD4 increase was 126 (70-169) cells per cubic millimeter in DRV/r group versus -42 (-121; 42) (P < 0.0001).


CONCLUSIONS
Treatment with TPV/r did not significantly increase the resistance score to DRV/r and did not preclude the efficacy of subsequent treatment with DRV/r.
Spagnuolo
Vincenzo
V
Department of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy. spagnuolo.vincenzo@hsr.it
Gianotti
Nicola
N
Seminari
Elena
E
Galli
Laura
L
Fusetti
Giuliana
G
Salpietro
Stefania
S
Lazzarin
Adriano
A
Castagna
Antonella
A
D000069454:Darunavir; D024921:Drug Resistance, Multiple, Viral; D024882:Drug Resistance, Viral / Q000235:genetics*; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D009154:Mutation; D011725:Pyridines / Q000494:pharmacology* / Q000627:therapeutic use; D011753:Pyrones / Q000494:pharmacology* / Q000627:therapeutic use; D013449:Sulfonamides / Q000494:pharmacology* / Q000627:therapeutic use; D017211:Treatment Failure
D011725:Pyridines; D011753:Pyrones; D013449:Sulfonamides; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D016333:HIV Protease; D000069454:Darunavir; C107201:tipranavir