Intermittent viremia during first-line, protease inhibitors-containing therapy: significance and relationship with drug resistance.
BACKGROUND
In HIV-infected patients on first-line antiretroviral therapy, the significance of intermittent viremia and their relationship with drug resistance remain unclear.


OBJECTIVE
To study the virological characteristics of intermittent viremia (IV) and the association between IV and later virological failure (VF) in patients on a first-line, PI-containing therapy.


METHODS
Antiretroviral-naive patients were enrolled in the APROVIR substudy of the prospective, multicenter APROCO cohort at the time they initiated a PI-containing therapy and were followed-up at month 1 and every 2 months. IV was defined as plasma HIV-1 RNA > 500 copies/ml on a single specimen. VF were defined as: (1) viral rebound on two consecutive plasma specimens with HIV-1 RNA > 500 copies/ml after an initial response below 500 copies/ml, or (2) persistence of plasma HIV-1 RNA> or =500 copies/ml during the first year of follow-up. Genotypic resistance analysis was performed at baseline and at the time of IV. PI plasma concentrations were determined at the time of IV.


RESULTS
IV was found in 20/219 patients in a 2 years follow-up. The occurrence of IV in the first year of therapy was associated with a higher risk of virological failure during the second year (p = 0.03). Genotypic resistance at the time of IV was found in only 4/16 patients and was not predictive of a subsequent virological failure. PI plasma levels suggested lack of adherence in 50% of patients with IV.


CONCLUSIONS
The occurrence of IV > 500 copies/ml among patients on first-line, PI-containing ART is suggestive of a lack of adherence rather than the selection of resistant variants and should lead to an intensification of adherence monitoring in order to reduce the risk of subsequent VF.
Masquelier
Bernard
B
Département de Virologie et Immunologie, Hôpital Pellegrin, Bordeaux, France. bernard.masquelier@chu-bordeaux.fr
Pereira
Edwige
E
Peytavin
Gilles
G
Descamps
Diane
D
Reynes
Jacques
J
Verdon
Renaud
R
Fleury
Hervé
H
Garraffo
R
R
Chêne
Geneviève
G
Raffi
François
F
Brun-Vézinet
F
F
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral / Q000235:genetics*; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology / Q000235:genetics / Q000502:physiology; D006801:Humans; D010349:Patient Compliance; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D019562:Viral Load; D014766:Viremia / Q000188:drug therapy / Q000821:virology*
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors