Plasma-derived HIV Nef+ exosomes persist in ACTG384 study participants despite successful virological suppression
| Autor: | Vincent C. Bond, Tamika Campbell-Sims, Michelle J. Lang, Richard B. Pollard, Michael D. Powell, David M. Asmuth, Andrea D. Raymond, Jane Chu, Mahfuz Khan |
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| Rok vydání: | 2019 |
| Předmět: |
0303 health sciences
Efavirenz business.industry Stavudine Immune dysregulation medicine.disease medicine.disease_cause 3. Good health Pathogenesis 03 medical and health sciences Regimen chemistry.chemical_compound 0302 clinical medicine Acquired immunodeficiency syndrome (AIDS) chemistry Immunology medicine 030212 general & internal medicine business Viral load Didanosine 030304 developmental biology medicine.drug |
| DOI: | 10.1101/708719 |
| Popis: | 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 (Δ >100 CD4 cell recovery/High Immunological Responders (High-IR) or low (Δ ≤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 naïve 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) inLow-IRs but not inHigh-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. |
| Databáze: | OpenAIRE |
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