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Efforts to cure HIV have focused on reactivating latent proviruses to enable elimination by CD8+ cytotoxic T-cells. Clinical studies of latency reversing agents (LRA) in individuals treated with antiretroviral therapy (ART) have shown increases in HIV transcription, but without reductions in virologic measures, or evidence that HIV-specific CD8+ T-cells were productively engaged. Here, we show that the SARS-CoV-2 mRNA vaccine BNT162b2 activates the RIG-I/TLR – TNF – NFκb axis, resulting in transcription of HIV proviruses with minimal perturbations of T-cell activation and host transcription. T-cells specific for the early gene-product HIV-Nef uniquely increased in frequency and acquired effector functon(granzyme-B) in ART-treated individuals following SARS-CoV-2 mRNA vaccination. These parameters of CD8+ T-cell induction correlated strongly with significant decreases in cell-associated HIV mRNA, suggesting killing or suppression of cells transcribing HIV. These results are, to our knowledge, the first observation of an intervention-induced reduction in a measure of HIV persistence, accompanied by precise immune correlates, in ART-suppressed individuals. However, we did not observe significant depletions of intact proviruses, underscoring challenges to achieving (or measuring) HIV reservoir reductions. Overall, our results support prioritizing the measurement of granzyme-B-producing Nef-specific responses in latency reversal studies and add impetus to developing HIV-targeted mRNA therapeutic vaccines that leverage built-in LRA activity.

The cyclic thermal shock behavior of two Si{sub 3}N{sub 4} ceramics, two SiC-whisker-reinforced alumina composites (Al{sub 2}O{sub 3}/SiC{sub w}), a SiC-particulate-reinforced alumina (Al{sub 2}O{sub 3}/SiC{sub p}), and an alumina continuously reinforced with SiC fibers (Al{sub 2}O{sub 3}/SiC{sub f}) composite has been studied. Specimens were repeatedly quenched from 1,473 K into a fluidized bed with a heat transfer coefficient of 1,400 W/(K{center_dot}m{sup 2}) [250 Btu/(h{center_dot}ft{sup 2}{center_dot}F)]. The thermal shock damage was assessed by room-temperature flexure strength measurements. Si{sub 3}N{sub 4} and Al{sub 2}O{sub 3}/SiC{sub p} showed no noticeable damage after 100 cycles, whereas Al{sub 2}O{sub 3}/SiC{sub w} and Al{sub 2}O{sub 3}/SiC{sub f} degraded substantially. The experimental results are discussed and rationalized in terms of finite element simulations and microstructural observations. The analysis suggests that the thermal shock performance of other materials may be estimated from comparisons with the present work.