icon-    folder.gif   Conference Reports for NATAP  
  Conference on Retroviruses
and Opportunistic Infections (CROI)
Boston, Massachusetts
March 4-7, 2018
Back grey_arrow_rt.gif
Reported by Jules Levin CROI 2018 March 4-7 Boston, MA
William Schreiber-Stainthorp, Sanhita Sinharay, Sharat Srinivasula, Swati Shah, Jing Wang, Lori Dodd, H. Clifford Lane, Michele Di Mascio, Dima A. Hammoud Center for Infectious Diseases Imaging (CIDI), Clinical Center, National Institutes of Health (NIH), Bethesda, MD, USA and Biostatistics Research Branch, Division of Clinical Research, NIAID, NIH, Rockville, MD, USA
"Treatment interruption is associated with increased brain glucose metabolism, as measured by FDG uptake, starting as early as one month after treatment modification.....the phenomenon raises concerns about the potential effects of even brief periods of non-adherence to ART....The hypermetabolism observed in this study, therefore, may be the result of neuroinflammation in the setting of viral rebound.....We believe that any potential insults to the CNS caused by ART initiation are outweighed by its positive effects on disease course; overall, our data support modern treatment guidelines, which advocate starting treatment as early as possible and maximizing adherence to ART regimens."


Program Abstract:
Subtle neurocognitive dysfunction has become more prevalent in the post-antiretroviral (ART) era suggesting continuing neurological damage despite treatment. On the other hand, HIV+ patients often fail to adhere to their treatment due to financial, social, and psychological factors. Our study investigates the effects of treatment initiation and interruption on brain inflammation/immune activation using 18F-FDG (FDG) metabolism in SIV-infected macaques, in correlation with clinical and laboratory markers of disease. Seven rhesus macaques were infected with SIV and underwent ART-interruption (n=5) and/or initiation (n=5). FDG-PET imaging was performed at baseline and at multiple time points up to 9 months after treatment modification. Mean and maximum Standardized Uptake Values (SUV) for the whole-brain were calculated. Plasma/CSF viral load (VL) and cytokine levels were measured. We evaluated changes in SUV from baseline to one month using a paired t-test. Mixed-effect linear regression models evaluated changes over multiple time-points and the association of SUV with disease markers.
Treatment interruption was associated with increased whole-brain SUV mean and max after 1 month (p=0.038; p=0.041) (Fig.1). The change was most pronounced during this early period however time was not statistically significant when evaluated in mixed effect linear regression models over the rest of the follow-up period. Decreased CD4+ and CD8+ cell counts and increased CSF VL were associated with increased SUVmean and max. Similarly increased CSF IL-15 was associated with increased SUVmean. The pattern within the treatment initiation group was far more variable and statistically significant associations were not observed (Fig.1), despite decreased plasma/CSF VL, increased CD4+ and CD8+ counts and decreased plasma/CSF cytokines.
In this study, ART interruption was associated with increased brain metabolism, which may reflect neuroinflammation in the setting of viral rebound. These effects were observed within one month of interruption. Although we cannot document permanent neurologic damage in association with increased glucose metabolism, this raises concerns about the potential damage of even brief periods of non-adherence to ART. Treatment initiation, however, did not result in significant changes in brain metabolism. This could be due to the long time needed for neuroinflammation to abate under the effects of viral control, beyond our follow-up period.