Abstract Body

Beside hemostasis, human platelets exert several immune functions and interact with infectious pathogens including HIV. We investigated whether platelets from cART-treated patients contain infectious HIV in vivo and addressed the significance and clinical implications of HIV sheltering by  platelets in AIDS.

 

Infectious HIV content in platelets was quantified by qPCR, FISH-Flow, microscopy, and reporter cell assays using platelet-rich-plasma (PRP) from 78 HIV-infected cART-treated adult patients. The capacity of platelet containing HIV to propagate infection was evaluated by culturing human primary macrophages with PRP with or without the platelet activation-blocker Abciximab (anti-integrin alpha(IIb)/beta(3) Fab). The presence of HIV in platelets was correlated with patient clinical status and parameters over >3 years.

We demonstrate that platelets from HIV-infected patients shelter infectious HIV in vivo, despite successful viral suppression by the combined antiretroviral therapy (cART) and in strong correlation with low blood CD4+T-cell counts (<350cells/microL). Patient platelets carrying HIV can propagate infection to macrophages in vitro in a process prevented by blocking platelet-macrophage interaction with Abciximab. Comparative phylogenetic analyses of virus found in peripheral blood and platelet samples prior to and > 1 year after cART initiation indicate that viruses contained in platelets do not originate from a latent reservoir established prior to therapy. Moreover, 88% of virally suppressed patients sheltering HIV in platelets are immunological nonresponders and fail to restore a proper immune status over > 1year of cART with a >50-fold higher likelihood than patients without HIV in platelets (OR: 56, 95%CI: 4.3-719.2, p=0.002).

Altogether, our results reveal that platelets act as a neglected transient shelter for infectious HIV in the blood of HIV-infected cART-suppressed patient. Platelets carrying HIV establish an alternative pathway for HIV dissemination in correlation with immunological failure, thus opening new treatment strategies for immunological nonresponders, for whom no efficient treatment is available yet . Furthermore, HIV contained in platelets can potentially fuel the tissue-macrophage reservoir we recently described in cART-suppressed patients (Ganor, Real et al., Nat Microbiol, 2019) in a process inhibited by the therapeutical anti-platelet agents.