An additive/subtractive genotypic score as a determinant of the virological response to didanosine in HIV-1 infected patients.
OBJECTIVE
To assess the genotypic determinants of the virological response (VR) to didanosine (ddI) in nucleoside reverse transcriptase inhibitors (NRTI)-experienced patients.


METHODS
Human immunodeficiency virus type 1 (HIV-1) genotype was determined at baseline in 74 ddI-naive-patients with baseline viral load >500 copies/ml and receiving ddI as part of a new regimen. VR was defined as a plasma HIV-1 RNA <50 copies/ml after three months on ddI. NRTI resistance mutations associated with higher or lower frequencies of VR with a p-value<0.25 were retained in different sets of mutations, where the mutations associated with a worse VR were added, whereas the mutations associated with a better VR were subtracted. The most significant mutation scores were then studied in a multivariate analysis.


RESULTS
Changes at three codons (M41L, L210W, T215Y/F/D/C/E) were associated with a worse VR and three mutations (K70R, M184V, K219Q) with a better VR. The strongest association with the VR was obtained with the score M41L+L210W+T215Y/F/D/C/E-K70R-K219Q. The score was independently associated with the VR in the multivariate analysis.


CONCLUSIONS
Taking into account the mutations associated with a better VR may improve genotypic resistance algorithms. Our results are of interest for the management of antiretroviral therapy in NRTI-experienced patients.
Capdepont
Sophie
S
Département de Virologie et Immunologie Biologique, CHU de Bordeaux, Place Amélie Raba Léon, 33076 Bordeaux Cedex, France.
Aurillac-Lavignolle
Valérie
V
Faure
Muriel
M
Dupon
Michel
M
Morlat
Philippe
P
Ragnaud
Jean-Marie
JM
Chêne
Geneviève
G
Fleury
Hervé
H
Masquelier
Bernard
B
D000465:Algorithms; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D016049:Didanosine / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D015999:Multivariate Analysis; D009154:Mutation; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D013997:Time Factors; D019562:Viral Load
D019380:Anti-HIV Agents; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D016049:Didanosine