Impact of antiretroviral therapy intensification with C-C motif chemokine receptor 5 antagonist maraviroc on HIV-associated neurocognitive impairment.

OBJECTIVES: Chemokine receptor CCR5 is the principal co-receptor for entry of M-tropic HIV virus into immune cells. It is expressed in the central nervous system and may contribute to neuro-inflammation. The CCR5 antagonist maraviroc (MVC) has been suggested to improve HIV-associated neurocognitive impairment (NCI). DESIGN: A double-blind, placebo-controlled, 48-week, randomized study of MVC vs. placebo in people with HIV (PWH) on stable antiretroviral therapy (ART) for more than one year in Hawaii and Puerto Rico with plasma HIV RNA less than 50 copies/ml and at least mild NCI defined as an overall or domain-specific neuropsychological z (NPZ) score less than -0.5. METHODS: Study participants were randomized 2 : 1 to intensification of ART with MVC vs. placebo. The primary endpoint was change in global and domain-specific NPZ modeled from study entry to week 48. Covariate adjusted treatment comparisons of average changes in cognitive outcome were performed using winsorized NPZ data. Monocyte subset frequencies and chemokine expression as well as plasma biomarker levels were assessed. RESULTS: Forty-nine participants were enrolled with 32 individuals randomized to MVC intensification and 17 to placebo. At baseline, worse NPZ scores were seen in the MVC arm. Comparison of 48-week NPZ change by arm revealed no differences except for a modest improvement in the Learning and Memory domain in the MVC arm, which did not survive multiplicity correction. No significant changes between arms were seen in immunologic parameters. CONCLUSION: This randomized controlled study found no definitive evidence in favor of MVC intensification among PWH with mild cognitive difficulties.

Greater Focus on Strengths is Associated with Successful Discharge in Youth Public Mental Health Treatment.

The positive psychology literature suggests focusing on strengths in mental health treatment improves well-being, reduces symptomology, and is linked to positive outcomes. However, there is little research on the use of strengths in treatment and their association with outcomes in youth clinical populations. The present study used multi-level modeling to examine the association between the proportional targeting of strengths and treatment outcomes for 1,841 youth ages 3-19 receiving intensive in-home services through a public mental health system. A greater percentage of targets endorsed during treatment that were strength-focused was associated with increased likelihood of successful treatment discharge, even after accounting for other predictors, including episode length, youth age, and level of impairment at treatment start. Specifically, as the percentage of strengths targeted increased from 46 to 64% of total targets endorsed, the odds of successful discharge increased by 21%. Such practice-based findings derived from aggregated data regarding services to multiethnic low-income families extend the strength-based intervention literature to include youth with significant life challenges. Study findings point to the need to develop structured interventions suitable for examination via clinical efficacy and effectiveness trials. Clinical practice, dissemination, implementation, and future research implications are discussed.