Viral Rebound in Patients on First-line, PI-containing HAART Suggests a Lack of Adherence Rather Than the Selection of Resistant Variants

The significance of intermittent viremia and its relationship with drug resistance are not fully understood in HIV positive individuals on first-line HAART. The objective of the current study was to determine 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.

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 was 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 >/=500copies/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.

The authors conclude, “The occurrence of IV >500copies/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.”

Department de Virologie et Immunologie, Hopital Pellegrin, Bordeaux, France.

04/04/05

Reference
B Masquelier and others (for the APROCO/COPILOTE Study Group). Intermittent viremia during first-line, protease inhibitors-containing therapy: significance and relationship with drug resistance. Journal of Clinical Virology 33(1): 75-78. May 2005.

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