In this analysis, we observed no significant differences in total cerebral cortex and gray matter or white matter volume for HIV+ participants compared with who are HIV−. A number of studies have observed a decrease in gray matter because of HIV infection,17,20,24,52 whereas others also observed no significant changes.12,53–56 Discrepancies between the various studies may be because of differences in the degree of impairment in HIV+ participants as well as the inclusion of matched HIV– participants.
In this study, we also observed no significant correlations between laboratory values such plasma HIV values (CD4 current, CD4 nadir, or log10 plasma HIV VL) and structural neuroimaging measures. A number of studies have observed no correlation between current CD4 or nadir CD4 and brain volumes.12,22,25,57 However, other investigators have observed a strong correlation between laboratory values, especially CD4 nadir, and brain volumes.17,21,46,53–56,58 A complex relationship may exist with a reduction in brain volumetric loss occurring not only at a lower CD4 nadir but also at a higher current CD4 cell count because of significant inflammation associated with reconstitution.55 Observed differences between various groups may reflect differences (1) in the sample size studied, (2) when a subject was scanned in relation to starting medications, (3) in methods used for brain segmentation,46 and (4) in regions investigated. Additional longitudinal studies of larger cohorts of HIV+ participants on stable HAART need to be performed.
Our exploratory analysis using a broken stick model demonstrated that brain atrophy may slowly develop over time. Based upon the self-reported duration of infection, our model estimates that a period of approximately 13 years is required for atrophy within the caudate to reach levels observed in this study. These changes can occur despite initiation of HAART because most HIV+ participants were prescribed medications when they met the current guidelines (CD4 cell count <350 cells/mm3 or an AIDS-defining illness). A wide variability existed for this effect. Our exploratory results suggest that a chronic subclinical process continues to occur within the caudate despite peripheral control of viral replication.24 Observed atrophy within the caudate could reflect low-level inflammation and neuronal loss.10,21 Initiation of adjunctive therapies soon after initial infection could be beneficial in an attempt to preserve brain integrity within the caudate.16 Additional longitudinal studies are required in acute and early HIV+ participants to confirm the effects of HIV on this brain structure.
Author Contributions: B. Ances proposed the project, performed statistical analyses, drafted the manuscript, and supervised the project, M. Ortega analyzed the data and revised the manuscript, F. Vaida performed statistical analyses, J. Heaps analyzed the data and revised the manuscript, and R. Paul revised the manuscript.
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