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bioRxiv · 10.1101/708719

Plasma-derived HIV Nef+ exosomes persist in ACTG384 study participants despite successful virological suppression.

Raymond, A. D.·Lang, M. J.·Chu, J.·Campbell-Sims, T.·Khan, M. B.·Bond, V. C.·Pollard, R. B.·Asmuth, D. M.·Powell, M. D.
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Abstract

Human Immunodeficiency Virus (HIV) accessory protein Negative factor (Nef) is detected in the plasma of HIV+ individuals associated with exosomes. The role of Nef+ exosomes (exNef) in HIV pathogenesis is unknown. We perform a retrospective longitudinal analysis to determine correlative clinical associations of exNef plasma levels in ARV-treated HIV+ patients with or without immune recovery. exNef concentration in a subset of AIDS Clinical Trial Group (ACTG) 384 participants with successful virological suppression and with either high ({Delta} >100 CD4 cell recovery/High Immunological Responders (High-IR) or low ({Delta} [≤]100 CD4 cell recovery/ Low Immunologic Responders (Low-IR) immunologic recovery was measured and compared for study weeks 48, 96, and 144. CD4 recovery showed a negative correlation with exNef at study week 144 (r = -0.3573, *p=.0366). Plasma exNef concentration in high IRs negatively correlated with naive CD4 count and recovery (r = -0.3249, *p = 0. 0348 (High-IR); r =0.2981, *p= #0.0513 (Low-IR)). However, recovery of CD4 memory cells positively correlated with exNef (r =.4534, *p=.0358) in Low-IRs but not in High-IRs. Regimen A (Didanosine, Stavudine, Efavirenz) lowered exNef levels in IRs by 2-fold compared to other regimens. Nef+ exosomes persist in ART-treated HIV+ individuals despite undetectable viral loads, negatively correlates with naive and memory CD4 T cell restoration and may be associated with reduced immunological recovery. Taken together, these data suggest that exNef may represent a novel mechanism utilized by HIV to promote immune dysregulation.

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Raymond, A. D., Lang, M. J., Chu, J., Campbell-Sims, T., Khan, M. B., Bond, V. C., Pollard, R. B., Asmuth, D. M., Powell, M. D.. 2019-07-20. Plasma-derived HIV Nef+ exosomes persist in ACTG384 study participants despite successful virological suppression.. https://doi.org/10.1101/708719

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