[Polymorphism of protease genes in patients infected with HIV-1 and response to therapy including a protease inhibitor].
Protease inhibitors (PIs) are recently introduced drugs that have improved the survival of HIV-infected patients when given in combination with two reverse transcriptase inhibitors. The HIV-1 protease gene is naturally highly polymorphic. Selection pressure due to IP use can result in major or minor resistance-associated mutations (RAMs). This study investigated whether presence before IP therapy of minor RAMs on the protease gene predicts the virological response. Of the 58 PI-naive patients included in the study, 12 had received two nucleoside reverse transcriptor inhibitors, 14 had received indinavir, 16 ritonavir, and 28 saquinavir-SGC. Viral load was measured on D0 (prior to PI initiation) and at M3 and M6 (Roche Monitor 1.5 with 200 and 20 copies/ml as the thresholds). The protease gene was fully sequenced on D0 using the ABI 377 automatic sequencer after RNA amplification by nested RT-PCR. None of the viral strains exhibited major mutations, but 57 of 58 (98%) had at least one minor mutation (median number of substitutions, 4), 60% had 1 to 4 substitutions, and 40% had 5 to 9 substitutions. Substitutions seen with a prevalence > 20% were located at codons 15, 35, 37, 41, 63, and 77. Numbers of substitutions at M3 and M6 were not correlated with viral load or the nature of the PI used, and neither were they significantly different between patients with more or fewer than 20 copies/ml. These data suggest that the protease genotype at PI initiation does not predict the efficacy of a regimen including a PI and is of no assistance in deciding whether or not to include a PI in a triple combination regimen.
Service de Virologie, Hôpital Pitié-Salpêtrière, Paris, France.
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M
Mouroux
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Bossi
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A
Yvon-Groussin
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C
Delaugerre
M A
MA
Valantin
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R
Tubiana
A
A
Coutellier
M
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Bonmarchand
F
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Bricaire
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Katlama
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Agut
J M
JM
Huraux
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Calvez
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000821:virology; D019943:Amino Acid Substitution; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D016333:HIV Protease / Q000235:genetics*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D019469:Indinavir / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019258:Saquinavir / Q000627:therapeutic use*; D019562:Viral Load
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D019469:Indinavir; D016333:HIV Protease; D019258:Saquinavir
Etude du polymorphisme du gène de la protéase de patients infectés par le VIH-1 et réponse à un traitement comprenant un inhibiteur de la protéase.