Taken together, inhibition of cofilin-actin rod formation by the CXCR4 and CCR5 antagonists AMD3100 and maraviroc along with the promiscuous nature of PrPC and NOX activity and their essential role in signaling downstream of both Aβd/t and gp120, strongly suggests that rod formation is of central importance to synaptopathy and cognitive decline observed in HAND and AD. The gene discussed is CXCR4; the disease is HIV-associated neurocognitive disorder.