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HIV in the brain

RNA levels and patterns of zidovudine resistance

From Glaxo Wellcome, Inc. (Drs. Lanier and Liao, and D.R. McClernon and M. St. Clair), Research Triangle Park, NC; and Department of Neurology (Drs. Gartner, Pardo, and McArthur, and P. Feaser), Johns Hopkins University School of Medicine, Baltimore, MD.

Address correspondence to Dr. J.C. McArthur, Johns Hopkins Hospital, 600 N. Wolfe St., Meyer 6-109, Baltimore, MD; e-mail: jm{at}jhmi.edu

Objective:— To examine the association between HIV RNA levels, patterns of antiretroviral resistance, and neurologic status.

Methods:— Autopsy samples from 13 HIV-infected subjects were examined for HIV-1 viral RNA (vRNA), and viral reverse transcriptase (RT) genotype was determined. All subjects had been clinically characterized using standard instruments before death.

Results:— The median HIV-1 vRNA level in brain samples from subjects with moderate dementia was 7.79 log₁₀ copies/g (range 5.56 to 9.75 log₁₀ copies/g) compared with 5.44 log₁₀ copies/g (range 3.51 to 9.32 log₁₀ copies/g) for mildly demented subjects and 4.87 log₁₀ copies/g (3.51 to 6.86 log₁₀ copies/g) for those obtained from nondemented individuals. There were differences between subjects with moderate dementia and nondemented subjects (p = 0.0002) and between subjects with moderate and mild dementia (p = 0.0128). No significant differences among the groups were observed for vRNA levels in peripheral tissues. Some demented subjects had relatively low levels of HIV-1 vRNA, and paradoxically some nondemented subjects had high vRNA brain levels. Little subject effect in vRNA was noted in peripheral regions, but high regional variation in vRNA was noted within the brain. Patterns of the major zidovudine (ZDV) RT mutations in brain and peripheral tissues were concordant in most subjects. Subjects with longer duration of exposure to ZDV tended to have lower brain vRNA levels and a greater number of RT mutations than those with limited to no exposure.

Conclusions:— The presence and severity of HIV dementia correlates with the levels of productive HIV replication within the brain. Other pathophysiologic events (including macrophage activation) probably also contribute to neurologic dysfunction.

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