Effects of antiretroviral therapy on cognitive impairment.

Since the introduction of combination antiretroviral therapy, the manifestations of HIV-associated central nervous system (CNS) involvement have generally become less severe and more manageable. Patients initiating antiretroviral therapy have demonstrated improvement in cognitive functioning. Reduction of viral burden has been correlated with improved CNS functioning. Recent studies have focused on the importance of CNS-penetrating antiretroviral regimens to target active replication in this protected compartment. There were initial conflicting reports of whether CNS-penetrating antiretrovirals improved cognitive functioning, with more evidence supporting the importance of CNS penetration in reducing viral burden and improving cognitive outcomes. Cognitive loss remains a feature of HIV infection, and some patients still suffer from incident or progressing cognitive and motor dysfunction even on combination therapy. Because the virus enters the CNS within days of initial infection, latent infection may be chipping away at the brain during the long asymptomatic period in HIV. When to start antiretrovirals for the maximum cognitive benefit remains to be determined.