HIV and Low Omega-3 Levels May Heighten Hippocampal Volume Differences Between Men and Women With Substance Use

Sex differences in hippocampal volumes are well-documented, but their interaction with HIV status and omega-3 fatty acids-particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)-remains unclear, especially in underserved populations. This study examines how HIV and omega-3 fatty acids influence sex differences in hippocampal volume and explores whether cognitive performance related to episodic memory modifies the association of omega-3 levels with hippocampal volume, considering both HIV status and sex.

We enrolled 166 participants aged over 45 years from a Baltimore, Maryland cohort. Brain MRIs were performed using a 3.0-T Siemens scanner, and volumetric segmentation was conducted with FreeSurfer (version 6.0), adjusting for intracranial volume (ICV).

Our study found that: (1) Among HIV-negative participants, females had significantly lower hippocampal volumes than males in 1 of 26 regions, whereas HIV-positive females had lower volumes in 13 of 26 regions (p < 0.006 for HIV-negative vs. HIV-positive females), (2) In HIV-positive individuals with EPA levels ≤0.40 %, females exhibited lower volumes in 11 of 26 regions, compared to no differences in those with EPA levels >0.40 % (p = 0.0003 for ≤0.40 % vs. >0.40 %), (3) Across all participants, lower EPA and DHA levels were associated with greater sex differences in hippocampal volumes, which diminished or disappeared at higher EPA and DHA levels (p < 0.00001 for EPA ≤0.40 % vs. >0.40 %; p = 0.004 for DHA ≤2.0 % vs. >2.0 %), and (4) Among Adults with lower episodic memory, higher log-scaled EPA levels were independently associated with greater hippocampal volume.

HIV may amplify sex differences in hippocampal volumes, disproportionately affecting females. Higher EPA and DHA levels may mitigate these effects, suggesting a protective role against hippocampal atrophy. Further studies are warranted to confirm these findings and explore whether the benefits extend to males with HIV or individuals without HIV.