Burt et al. (1) reported an association between the APOE ε4/ε4 genotype and more rapid disease progression in HIV+ subjects. In contrast, this allele did not influence risk for HIV-associated dementia (HAD). They suggested that the ε4/ε4 genotype might still be associated with milder forms of HIV-associated neurological impairments. We recently studied HIV-1-infected individuals who were free from HAD (2) and found no support for this hypothesis. The APOE ε4 allele was associated neither with lower baseline memory or psychomotor performance nor with greater deficits after acute oral benzodiazepine challenge in this population. On the contrary, HIV-1 ε4-positive individuals had significantly better baseline memory performance.
While Corder et al. (3) found increased dementia and neuropathy associated with ε4, a postmortem study (4) found no excess HAD or encephalitis in ε4 subjects with HIV-1 infection. A recent epidemiologic study reported an increased risk for dementia associated with the ε4 allele only in HIV-infected persons 50 years and older, raising the possibility of an age-associated modulation of ε4 risk in HAD (5). The mean age of our ε4-positive HIV population was 44.46 ± 8.25 years, and the absence of significant impairments associated with ε4 is consistent with this hypothesis. The mean age of the cohort studied by Burt et al. (1) was not apparent, and it would be valuable to know whether a younger age of their sample contributed to the lack of association between ε4 and HAD.
Footnotes
The authors declare no conflict of interest.
References
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