Frequency of apolipoprotein E4 among older compared with younger HIV patients: Support for detrimental effect of E4 on survival

We read with interest a recent article by Burt et al. demonstrating accelerated HIV disease course with apoE4 (1). This finding is congruent with data from the Hawaii Aging with HIV Cohort (HAHC). We previously completed apoE genotyping among 222 HAHC enrollees, 103 of whom were <40 years old (younger cohort) and 119 of whom were at least 50 years old (older cohort). Here, apoE4 conveyed risk for research-designated HIV-associated dementia (HAD) within the older group but not the younger group (2). We were intrigued by the fact that having an apoE4 allele was less frequently noted in our older group (23%) compared with our younger group (37%, P = 0.020). Our younger group is more ethnically diverse, possibly accounting for some differences; however, this trend remained when analyzed among only Caucasian enrollees [22% older (n = 83), 38% younger (n = 40), P = 0.064]. We speculated that selection bias may be present or that apoE4 could influence survival, a conviction that seems more apt in light of these new data.

HAHC individuals with at least one apoE4 tend to have a shorter self-reported HIV duration (10.5 vs. 8.3 years, P = 0.012), even when analyzed separately among only older enrollees (12.6 vs. 9.8 years, P = 0.014). Among older individuals diagnosed before antiretroviral therapy was available (1988), only 7/45 (16%) have at least one apoE4 allele. Study entry CD4 lymphocyte count and plasma HIV RNA levels did not differ by apoE4, and we do not identify differences in intracellular (peripheral mononuclear cell) HIV DNA by E4 status, a robust marker of HAD in this cohort (37 vs. 25 copies per 10⁶ cells, P= 0.551) (3).