This study examined the role of biological processes in the development of specific neuropsychiatric complications in HAART-naive adults with HIV/AIDS. Depressive symptoms were modestly associated with elevated IL-6 mRNA expression (r(s)=0.40, p<0.05) even after removing the influences of other subjective complaints (pr=0.39, p<0.05). Elevated serum neopterin was strongly associated with depressive symptoms in individuals taking antidepressants (r(s)=0.83, p<0.001), though the association was nullified in those not on antidepressants (r(s)=-0.25, p>0.05). Mean neopterin levels were higher in the depressed as compared with nondepressed group but only for those taking antidepressants (F=45.66, df=1, 11, p<0.001). Neuropsychological impairment was not associated with the biological markers. These findings suggest that systemic immune markers (like neopterin) may be useful in differentiating treatment-resistant individuals at greater risk of developing chronic depression.