Impact of lopinavir/ritonavir use on antiretroviral resistance in recent clinical practice.
OBJECTIVE
This observational study was requested by French health authorities to determine the impact of lopinavir/ritonavir (Kaletra(®)) on antiretroviral resistance in clinical practice. Virological failures of lopinavir/ritonavir and their effects on the resistance to protease inhibitors and reverse transcriptase inhibitors were evaluated in protease inhibitor-experienced patients.


METHODS
Virological failure was defined as an HIV-1 plasma viral load >50 copies/mL after at least 3 months of lopinavir/ritonavir-containing antiretroviral therapy. For all patients, a resistance genotypic test was available at failure and before lopinavir/ritonavir treatment. Data from 72 patients with inclusion criteria were studied.


RESULTS
The mean viral load at baseline was 4 log(10) copies/mL (1.6-6.5). Mutations in the protease gene significantly selected between baseline and failure were L10V, K20R, L33F, M36I, I47V, I54V, A71V and I85V (P < 0.05). Patients who had more than seven protease inhibitor mutations at baseline showed a significantly increased risk of occurrence of protease inhibitor mutations. The proportion of viruses susceptible to atazanavir, fosamprenavir and darunavir decreased significantly between baseline and failure (P < 0.05). Among patients with a virus susceptible to atazanavir at day 0, 26% (n = 14) exhibited a virus resistant or possibly resistant at the time of failure. This proportion was 32% (n = 16) for fosamprenavir and 16% (n = 7) for darunavir.


CONCLUSIONS
A darunavir-based regimen appears to be a sequential option in the case of lopinavir/ritonavir failure. To compare and determine the best treatment sequencing, similar studies should be performed for darunavir/ritonavir and atazanavir/ritonavir.
AP-HP, Pitié-Salpêtrière Hospital, INSERM U943 and Pierre et Marie Curie University, Paris, France. sidonie.lambert@psl.aphp.fr
Sidonie
S
Lambert-Niclot
Bernard
B
Masquelier
Isabelle
I
Cohen Codar
Cathia
C
Soulie
Constance
C
Delaugerre
Laurence
L
Morand-Joubert
Charlotte
C
Charpentier
Virginie
V
Ferre
Jean-Christophe
JC
Plantier
Brigitte
B
Montes
Sophie
S
Carret
Valerie
V
Perrot
Gilles
G
Peytavin
Dominique
D
Costagliola
Vincent
V
Calvez
Anne-Geneviève
AG
Marcelin
D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003430:Cross-Sectional Studies; D024882:Drug Resistance, Viral; D005260:Female; D005602:France; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D061466:Lopinavir / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008826:Microbial Sensitivity Tests / Q000379:methods; D008875:Middle Aged; D019438:Ritonavir / Q000494:pharmacology / Q000627:therapeutic use*; D017211:Treatment Failure; D019562:Viral Load
D019380:Anti-HIV Agents; D061466:Lopinavir; D019438:Ritonavir