Research into the effect of antiretroviral therapy on brain function has yielded mixed results. Several studies have shown that people on combination therapy that suppresses their blood viral load generally also have undetectable HIV in their cerebrospinal fluid - even if they are not using drugs known to penetrate the blood-brain barrier ^[1][2]. One research team found that antiretroviral therapy reduced cerebrospinal viral load more than blood viral load, even in patients with partial drug resistance^[3].

Suppressing HIV in the blood, the cerebrospinal fluid or both has been linked to improved neurocognitive functioning. Improvement after starting HAART has been observed in patients who are not using anti-HIV drugs known to penetrate the brain, suggesting that overall viral suppression may be more important than use of specific drugs ^[4] [5]. However, other studies indicate that brain-penetrating drugs do make a difference in terms of suppressing cerebrospinal fluid viral load and improving brain function^[6][7].

Given these conflicting results, some researchers think suppressing HIV in the blood is adequate for people with relatively well preserved immune function and mild cognitive impairment, but believe brain-penetrating drugs may be necessary for people with more advanced disease, lower CD4 cell counts and more severe neurocognitive disorders. Further, some degree of neurocognitive impairment may be irreversible even with effective treatment, underling the benefits of starting therapy before neurological damage occurs^[8].