Background: Fatty-acids, including n6 series, modulate immune function but their effect on CD4 cell counts, death or hospitalization in HIV-infected patients on antiretroviral therapy is unknown.

Methods: In a randomized trial for effects of multivitamins in HIV-infected patients in Uganda, we used gas chromatography to measure plasma n6-fatty acids at baseline, determined CD4 counts at baseline, 3, 6, 12 and 18 months and recorded hospitalization or death events. The associations of fatty acids with CD4 counts and events were analyzed using repeated-measures ANOVA and Cox regression, respectively.

Results: Among 297 patients with fatty acids measurements, 16 patients died and 69 were hospitalized within 18 months. Except for linoleic acid, n6-fatty acids levels were positively associated with CD4 counts at baseline but not during follow-up. In models that included all five major n6-fatty acids, age, sex, BMI, anemia status and use of antiretroviral therapy, multivitamin supplements and alcohol, the risk of death or hospitalization decreased significantly with increase in linoleic acid and gamma-linolenic acid levels while associations for dihomo-gamma-linolenic acid, arachidonic acid and aolrenic acid were null. The hazard ratios (95% confidence intervals) per one SD increase in linoleic acid and gamma-linolenic acid were 0.73 (0.56-0.94) and 0.51 (0.36-0.72), respectively. Gamma-linolenic acid remained significant (HR=0.51; 95% CI: 0.35-0.68) after further adjustment for other plasma fatty acids.

Conclusion: Lower levels of gamma-linolenic acid are associated with lower CD4 counts and an increased risk of death or hospitalization. These results suggest a potential for using n6-fatty acids to improve outcomes from antiretroviral therapy.