Characterization of HIV-1 from patients with virological failure to a boosted protease inhibitor regimen.
The use of highly active antiretroviral treatment (HAART) regimens with unboosted protease inhibitors (PIs) has resulted in a high level of virological failure primarily due to the development of resistant virus. Current boosted PI regimens combine successfully low-dose ritonavir (r) with a second PI. The aim of the study was to estimate the proportion of patients, in a population based setting, who develop virological failure on a PI/r regimen. Through The Danish HIV Cohort Study 1,007 patients who received PI/r based treatment between 1995 and 2008 were identified. Twenty-three (2.3%) experienced virological failure, of whom 19 (83%) started PI/r treatment before 2001. Patients from Copenhagen (n=19) were selected to study the development of protease (PR) and gag cleavage site (CS) mutations during PI/r treatment and PI plasma levels at the time of virological failure. Three patients (16%) developed major PI resistance mutations. Mutations in the p7/p1 and p1/p6 gag CS only developed in patients with major or minor mutations in PR. Drug concentrations were low or undetectable in 10 out of the 19 patients. In total PR resistance mutations and low drug levels could account for 12 (63%) of the failure cases. In conclusion, virological failure to PI/r is a low and decreasing problem primarily caused by low plasma drug levels and to a lesser extent major PR mutations. Gag CS mutations did not contribute significantly to resistance development and virological failure.
Department of Virology, State Serum Institute, Copenhagen, Denmark. mml@ssi.dk
Marie Rathcke
MR
Lillemark
Jan
J
Gerstoft
Niels
N
Obel
Gitte
G
Kronborg
Court
C
Pedersen
Louise Bruun
LB
Jørgensen
Tina Vasehus
TV
Madsen
Terese Lea
TL
Katzenstein
D019380:Anti-HIV Agents / Q000097:blood / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D015331:Cohort Studies; D003718:Denmark; D024882:Drug Resistance, Viral; D005260:Female; D015750:Genes, gag; D015751:Genes, pol; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D011480:Protease Inhibitors / Q000097:blood / Q000627:therapeutic use; D019438:Ritonavir / Q000097:blood / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load
D019380:Anti-HIV Agents; D011480:Protease Inhibitors; D019438:Ritonavir