Time course of total HIV-1 DNA and 2-long-terminal repeat circles in patients with controlled plasma viremia switching to a raltegravir-containing regimen

Abstract

Early integration of HIV proviral DNA into the host cell genome prevents viral eradication, despite suppressive HAART. In vitro, integrase inhibitors reduce proviral DNA levels and rapidly increase 2-long-terminal repeat (LTR) circle levels. We examined the effect of raltegravir on the time course of HIV-1 DNA forms in patients with controlled viremia. The EASIER-ANRS 138 randomized trial demonstrated that switching from enfuvirtide to raltegravir maintained virological suppression in treatment-experienced patients with viral load below 400 copies/ml. We analyzed total HIV-1 DNA and 2-LTR circle levels measured at weeks (W)0 and 24 in the first 30 patients enrolled in each arm, and at W48 in the raltegravir arm. At W0 the total DNA level was 3.6 log(10)/10(6) peripheral blood mononuclear cell (PBMC) in both groups, and 2-LTR circles were detected in six patients (median 89 copies/10(6) PBMC). At W24 the total DNA level was 3.6 log(10)/10(6) PBMC in both groups, and 2-LTR circles were detected in three new patients. At W48 the total HIV DNA level in the raltegravir group was 3.5 log(10)/10(6) PBMC, and 2-LTR circles were undetectable. No significant change in total HIV DNA occurred between W0 and W24 in either arm (P = 0.71) and no significant change was observed in the raltegravir arm at W48. In most patients on effective HAART, including regimens containing an integrase inhibitor, the viral reservoir, reflected by the HIV-1 DNA load, is stable and nondynamic during the 48 weeks of follow-up.