| Publication Abstract Display | | Type: Published Manuscript | | Title: Randomized trial of CNS-targeted antiretrovirals for HIV-associated neurocognitive disorder. | | Authors: Ellis RJ, Letendre S, Vaida F, Haubrich R, Heaton RK, Sacktor N, Clifford DB, Best BM, May S, Umlauf A, Cherner M, Sanders C, Ballard C, Simpson DM, Jay C, McCutchan JA | | Year: 2014 | | Publication: Clinical Infectious Diseases : An Official Publication of The Infectious Diseases Society of America | | Volume: 58 Issue: 7 Pages: 1015-1022 | | Abstract:Background. Antiretroviral (ARV) medications differentially penetrate across the blood-brain barrier into CNS tissues, potentially influencing their effectiveness in treating brain infection. Methods. This randomized, controlled, clinical trial (RCT) called for 120 participants at 5 study sites to be randomized 1:1 to CNS-T or non-CNS-T ART. Entry clinical factors such as ARV experience were balanced across arms using an adaptive randomization approach. The primary outcome, change in neurocognitive performance, was measured as the difference in global deficit score (GDS) from baseline to week 16. Results. The study was terminated early on the recommendation of its DSMB based on slow accrual and a low likelihood of detecting a difference in the primary outcome. No safety concerns were identified. Of 326 participants screened, 59 met entry criteria and were randomized. The primary intent-to-treat analysis included 49 participants who completed week 16. These comprised 39 men and 10 women with a mean age of 44 (±10) years, and median nadir and current CD4+ T-cell counts of 175 and 242/µL. The proportional improvement in GDS from baseline was non-significantly larger (7%; 95% CI -31%, 62%) in the CNS-T versus non-CNS-T arm, representing a treatment effect size (ES) of 0.09 (95% CI, -0.48, 0.65). Pre-specified secondary analysis showed a trend interaction (p=0.087) indicating that participants who had baseline plasma virologic suppression may have benefitted from CNS-T. Conclusions. This study found no evidence of neurocognitive benefit for a CNS-T strategy in HAND. A benefit for a subgroup or small overall benefits could not be excluded. |
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