Early antiretroviral therapy with raltegravir generates sustained reductions in HIV reservoirs but not lower T-cell activation levels. (15th May 2015)

• Record Type: Journal Article
• Authors: Hey-Cunningham, William J.; Murray, John M.; Natarajan, Ven; Amin, Janaki; Moore, Cecilia L.; Emery, Sean; Cooper, David A.; Zaunders, John; Kelleher, Anthony D.; Koelsch, Kersten K.
• Is Part Of: AIDS. Volume 29:Number 8(2015)
• Publication Date: 2015-05-15
• Subjects: AIDS (Disease) -- Periodicals; Acquired Immunodeficiency Syndrome; AIDS (Disease); Periodicals; Periodicals; 616.9792005
• DOI: 10.1097/QAD.0000000000000625
• Languages: English
• ISSNs: 0269-9370

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>Objective:</title> <p>The initiation of antiretroviral therapy (ART) during primary infection may offer clinical benefits for HIV-infected individuals by reducing HIV DNA reservoir size and chronic T-cell activation. Current evidence for the advantages of early ART, however, are mostly derived from cross-sectional studies, with the long-term benefits yet to be ascertained.</p> </sec> <sec> <title>Design/methods:</title> <p>We conducted an open-label, nonrandomized study, monitoring for 3 years: plasma viral load (pVL), T-cell phenotypes, and peripheral CD4<sup>+</sup> T-cell associated total, integrated and 2-long terminal repeat HIV DNA species. The study included 16 treatment-naive individuals initiating ART with raltegravir and Truvada during either primary (PHI, <italic>n</italic> = 8) or chronic (CHI, <italic>n</italic> = 8) HIV infection.</p> </sec> <sec> <title>Results:</title> <p>ART initiated during PHI compared with CHI generated significant reductions of peripheral CD4<sup>+</sup> T-cell HIV DNA reservoirs that were sustained for 3 years of therapy. Median log<sub>10</sub> HIV DNA copies/10<sup>6</sup> CD4<sup>+</sup> T cells at the final visit: total; CHI = 3.23 > PHI = 2.72, <italic>P</italic> < 0.01; integrated; CHI = 2.64 > PHI = 1.77, <italic>P</italic> < 0.01. Similar trends were observed for pVL, however, did not reach significance: log<sub>10</sub> HIV RNA copies/ml plasma at the final visit: CHI = 1.3 ≥ PHI = 0.39, <italic>P</italic> = 0.08. Both cohorts displayed similar and elevated levels of CD38/HLA-DR coexpression on CD4<sup>+</sup> and CD8<sup>+</sup> T cells relative to uninfected healthy controls.</p> </sec> <sec> <title>Conclusion:</title> <p>The reduction in HIV DNA reservoirs generated by the early initiation of ART was sustained for 3 years of therapy. Although the PHI cohort trended to lower levels of pVL, and pVL was associated with CD8<sup>+</sup> T-cell activation, no differences in T-cell activation were observed between the PHI and CHI groups.</p> </sec> </abstract>