Influence of highly active antiretroviral therapy on persistence of HIV in the central nervous system

PURPOSE OF REVIEW: The epidemiology of HIV infection is changing rapidly in the era of highly actively antiretroviral therapy, as the use of such therapy is increasing in all countries. This has had a significant impact on the neurological manifestations of HIV infection, posing new challenges in diagnosis and treatment. This review provides a critical analysis of the recent literature on the impact of highly actively antiretroviral therapy on HIV-related neurological complications and changes in treatment strategies. RECENT FINDINGS: It is becoming clear that the brain is an important reservoir for the virus, and neuroinflammatory and neurodegenerative changes may continue despite the adequate use of highly actively antiretroviral therapy. Although this antiretroviral therapy has had a significant impact on the severity of HIV dementia, cognitive impairment persists. With improvement in the immune status following treatment with antiretrovirals, in rare cases the brain can become a target of the immune reconstitution. SUMMARY: Highly actively antiretroviral therapy may need to be optimized in patients with HIV-associated cognitive impairment to achieve maximal central nervous system penetration; however, this therapeutic strategy may not be sufficient for halting the process. In some instances, the antiretroviral drugs themselves may become the problem. New strategies for neuroprotection that also target host genes which control HIV replication are being developed.