Differential course of HIV-1 infection and APOE polymorphism

Burt et al. (1) demonstrate that the APOE ε4/ε4 and other ε2⁺ or ε4⁺ genotypes accelerate HIV mortality, a gene dosage effect of the ε4 allele on steady-state viral load, and they associate ε4 with enhanced HIV-1 cell entry. They did not find an excess of HIV-associated dementia (HAD) among ε4⁺ patients.

In a related report (2) not cited by Burt et al., 209 HIV⁺ patients were divided into four groups depending on the yearly rate of CD4⁺ cell decline. The ε4⁺ and ε2⁺ genotypes were one-third less frequent at both ends of the progression spectrum (P = 0.04). Long-term stable and slowly progressing patients were more likely to carry ε3/3 than those progressing at a “normal” rate. Rapidly progressing patients surviving to when the study was carried out also were more likely to carry ε3/3.

As cited, Corder et al. (3) investigated 44 HIV⁺ subjects identified close to the time of seroconversion. The cohort was designed to investigate neurologic changes in HIV infection; subjects were evaluated over a 2-day period every 6 months for up to 5 years. Very mild suspected dementia (almost exclusively) was more common among ε4⁺ subjects (30% vs. 15%); peripheral neuropathy was also more common (70% vs. 39%) and, when present, more severe. Whether very mild suspected dementia among persons relatively early in the course of HIV infection constitutes HAD, and whether it would have been consistently identified among the >1,000 subjects investigated by Burt et al. (1), is at issue.