HIV-Related Neuropathology, 1985 to 1999: Rising Prevalence of HIV Encephalopathy in the Era of Highly Active Antiretroviral Therapy
January 21, 2003
Autopsy studies of HIV-infected individuals have proven useful in understanding the range of opportunistic infections and neoplasia in late-stage AIDS. The current study uses autopsy findings and clinical data to better define the relationship of neuropathologic findings, clinical progression, and concomitant opportunistic infections and neoplasia, especially with regard to treatment options.Adapted from:
The authors matched postmortem neuropathologic reports for a consecutive series of 436 HIV-seropositive patients who died between 1985 and 1999 with clinical data for 371 of them. They divided the cases into four groups, depending on the date of death, to reflect the type of antiretroviral therapy available: before 1987 (before zidovudine); 1987-1992, the time of monotherapy (NNRTIs); 1993 to 1995, the era of dual NRTI combinations; and 1996 to 1999, the era of HAART with protease inhibitors. Fifty-seven percent of cases in the last group had been prescribed HAART.
Autopsies declined after the advent of combination therapies, the study reports. Opportunistic infections -- cytomegalovirus, toxoplasmosis, cryptococcosis and central nervous system lymphoma -- decreased over time. Other conditions -- cerebral tuberculosis, aspergillosis, herpes and progressive multifocal leukoencephalopathy -- showed a downward trend, the authors report, but the numbers were too low for statistical analyses.
Incidence of mild and moderate HIV encephalopathy increased over time, the study found, especially between 1996-1999. Severe encephalopathy, however, was uncommon overall and was not observed in the era of HAART. Based on trends, the authors suggest that HAART may prevent severe direct HIV-1 pathology of the CNS, but has a limited effect on preventing mild to moderate CNS damage. They speculate that amelioration of the pathologic findings of HIV encephalopathy might be related to decreased viral burden through systemic therapy. "Viral burden in tissue compartments might be reduced and concomitantly the severity of pathologic changes," they wrote. "The entry of HIV in compartments over time cannot be prevented, though, and therefore we see pathologic changes in the mild and moderate categories."
The researchers further suggest that HIV-1 infection may be more pathogenic for CNS tissue in later stages of the disease, suggesting that once HIV-1 gains neurotropic properties, HAART does not fully reverse the effects of neurotropism.
"Perhaps," they concluded, "this is a result of incomplete suppression of viral replications, especially in tissues such as the brain, where penetration of drugs may be impaired by the blood-brain barrier. Long-term survival appears to increase the risk for HIV-1-associated CNS pathology."
Journal of Acquired Immune Deficiency Syndromes
10.01.02; Vol. 31: P. 171-177; Jutta K Neuenburg; Hans R. Brodt; Brian G. Herndier; Markus Bickel; Peter Bacchetti; Richard W. Price; Robert M. Grant; Wolfgang Schlote