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This review summarizes recent molecular studies that elucidate the role of HIV-1-related factorssuch as the viral proteins trans-activator of transcription (Tat), gp120, and Vpr, HIV-1 RNAs, and associated microRNA and long non-coding RNAs and extracellular vesiclesin microglial activation through mechanisms including cellular senescence, ferroptosis, defective mitophagy, NLR family pyrin domain containing 3 activation, and NF-B pathway modulation