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  • Title: 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.
    Author: Delaugerre C, Charreau I, Braun J, Néré ML, de Castro N, Yeni P, Ghosn J, Aboulker JP, Molina JM, Simon F, ANRS 138 study group.
    Journal: AIDS; 2010 Sep 24; 24(15):2391-5. PubMed ID: 20683319.
    Abstract:
    BACKGROUND: 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. PATIENTS AND METHODS: 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. RESULTS: 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. DISCUSSION: 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.
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