Background: Ongoing HIV-1 replication in lymphoid cells is one explanation of the persistence of HIV-1 reservoirs\ndespite highly active antiretroviral therapy (cART). We tested the potential of cART intensification by Maraviroc plus\nRaltegravir to decrease proviral HIV-1 DNA levels in lymphoid cells during a randomized trial.\nPatients and methods: We randomly assigned for 48 weeks 22 patients to continue their current first line regimen\nof Truvada�® plus Kaletra�® or intensify it with Maraviroc and Raltegravir. The primary objective was to obtain a 50%\ndecrease in proviral HIV-1 DNA levels in lymphoid cells with intensification. Blood samples were drawn at W-2, W0,\nW2, W4, W12, W24 and W48. Plasma viremia, cellular proviral DNA and cellular RNA, 2-LTR circles and lymphocytes\nsubsets were assayed using validated methods. Patients in the intensified group underwent a gut biopsy at baseline\nand W48 to measure proviral DNA levels. Statistical analysis used parametric and non-parametric tests.\nResults: Ten patients in each arm completed the trial. The 2 populations were comparable at baseline. No change\nin the reservoir size was observed in the intensified arm compared to the control arm measured in peripheral blood\nmononuclear cells (PBMCs). No change in the reservoir size was observed in gut proviral DNA in the intensified arm. In\nthis group, no increase in 2-LTR circles was observed as early as 2 weeks after intensification and no change was found\nin residual plasma RNA levels measured by the single copy assay. However, a decrease in CD8+ T cells activation was\nobserved at 24 and 48 weeks, as well as in PBMCs HIV-1 RNA levels.\nConclusion: We conclude that the intensification of a Protease Inhibitor regimen with Maraviroc and Raltegravir does\nnot impact the blood proviral DNA reservoir of HIV but can decrease the cell-associated HIV RNA, the CD8 activation\nand has a possible impact on rectal proviral HIV DNA in some patients.
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