Mechanisms of early virologic failure in antiretroviral-naive patients starting protease inhibitor-containing regimens: the APROVIR Study.
The virologic and pharmacologic mechanisms of virologic failure (VF) were studied in 243 antiretroviral-naive patients starting first-line protease inhibitor (PI)-containing therapy (nelfinavir in 66% and indinavir in 19%). Among the 220 patients with follow-up data, VF occurred in 35 (16%) during the first year of follow-up. A higher baseline virus load and poorer adherence to therapy were associated with VF. At the time of VF, key PI-resistance mutations were detected in 11 (48%) of 23 patients who started on nelfinavir but were absent in 6 patients with indinavir treatment failure. PI plasma levels were more often below the range of active concentrations in VF with wild-type viruses (74%) than in VF with PI-resistant viruses (25%; P=.02). The mechanisms of early VF and of selection of PI-resistant viruses differed by type of PI and were dependent on PI plasma levels.
Masquelier
Bernard
B
Laboratoire de Virologie, Hôpital Pellegrin, CHU de Bordeaux, Bordeaux, France. bernard.masquelier@chu-bordeaux.fr
Peytavin
Gilles
G
Leport
Catherine
C
Droz
Cecile
C
Duran
Ségolène
S
Verdon
Renaud
R
Besnier
Jean-Marc
JM
Chêne
Geneviève
G
Raffi
François
F
Brun-Vézinet
Françoise
F
D000328:Adult; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000821:virology*; D017320:HIV Protease Inhibitors / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D011446:Prospective Studies; D017211:Treatment Failure
D017320:HIV Protease Inhibitors