No Evidence of a Detrimental Effect of Pitavastatin on Neurocognitive Function Among People with HIV

Objective: Effects of statins on neurocognitive function remain poorly understood, with some studies suggesting harm and others suggesting benefit. Limited observational data among people with HIV (PWH) is biased by indication for statin prescription. We sought to assess statin effects on neurocognitive function among PWH. Design: We leveraged data from participants co-enrolled in REPRIEVE (randomized trial of pitavastatin vs placebo among PWH with low-to-moderate cardiovascular risk) and HAILO (observational study involving repeated neurocognitive measures). Methods: Participants with ≥1 measure of neurocognitive function before and after REPRIEVE randomization were included. Neurocognitive function was determined by NPZ-4, the average of the Z scores from: Hopkins Verbal Learning Test Revised, Trailmaking A and B, and Digit Symbol Test every 48 weeks. Trajectories before and after randomization were analyzed with generalized estimating equation models. Results: Of 181 co-enrolled participants (pitavastatin 88, placebo 93), changes over median 2.3 years on overall and individual neurocognitive scores were small, not meeting a clinically relevant threshold of >0.5/year, and similar between arms. Although subgroup analyses were limited by a small sample size, we observed trends towards improved Trailmaking A in participants with baseline impairment who were randomized to pitavastatin vs placebo and towards worsened NPZ-4 in females randomized to pitavastatin vs placebo that similarly did not reach threshold for clinical relevance. Other subgroup effects were minimal and not statistically or clinically significant. Conclusions: We found no evidence of a detrimental effect of pitavastatin use on a limited battery of neurocognitive assessments among PWH, even among PWH with baseline neurocognitive impairment.