Background:  We wanted to examine the epidemiology in the antiretroviral (ARV) era of HIV brain pathology (HBP), consisting of HIV encephalitis, HIV leukoencephalopathy, and microglial nodular encephalitis.

Methods:  A cross-sectional survey analyzing prospectively acquired clinical and neuropathological data collected by the participating sites of the National NeuroAIDS Tisue Consortium (NNTC), which consists of 589 brain samples from individuals with advanced HIV disease collected from 1999 onward. We assessed gender, ethnicity/race, mode of transmission, age, year of death, length of study follow-up, nadir CD4, plasma viral load within 6 months of death, on study and last documented ARV regime; presence of HBP and of other pathological findings; HIV-associated neurocognitive disorder (HAND) or major depressive disorder (MDD). To assess if the NNTC cohort was representative of the US AIDS epidemic NNTC demographic variables were compared with Centers for Disease Control and Prevention (CDC) US HIV/AIDS epidemic data. Non-parametric statistical analyses were used to compare the HBP and no HBP groups.

Results:  Only 22% of the brains examined were neuropathologically normal. Opportunistic infections and cerebral lymphoma occurred in 1 to 5% of the cohort. HBP was observed in 17.5% of the cohort and was associated with nadir CD4 during the study period (p = 0.003) and log plasma viral load within 6 months of death (p <0.001). HBP did not correlate with HAND and there was no pathological correlate for MDD in the subsets of patients for which prospective premortem neuropsychologic (n = 336) and psychiatric (n = 264) data were available. Brains without HBP often had other non-infectious pathological findings or minimal non-diagnostic abnormalities. Alzheimer type II gliosis and minimal non-diagnostic abnormalities correlated with HAND (p = 0.027 and <0.001, respectively). With regard to the CDC data, individuals autopsied in the NNTC were similar in age distribution, but there were fewer females and African Americans, but more Hispanics and men who have sex with men.

Conclusions:  HBP was associated with nadir CD4 during the study period and log plasma viral load within 6 months of death. The frequency of HBP, opportunistic infections, and lymphoma were lower than previous pre-ARV reports. There were high rates of both MDD and HAND. There was no pathological correlate of MDD, but other non-infectious pathological findings and minimal non-diagnostic abnormalities correlated with HAND.