us-map.html ¶ A list of severe manifestations of monkeypox can be found at https://emergency. cdc.gov/han/2022/han00475.asp. ** During the study period and as of October 21, 2022, CDC was notified by state and local jurisdictions of five decedents whose death certificates included monkeypox as a cause of death or contributing factor, six decedents whose cause of death is still under active investigation, and one decedent in whom the death was not monkeypox-related. Additional monkeypox cases involving severe disease or death might not be included in this report if CDC has not yet been notified about the case or if the case occurred outside of the study period.

Background The genomic heterogeneity of HIV-1 impedes the ability of consensus sequences in vaccines to elicit effective antiviral immune responses. AGS-004 amplifies translation-competent RNA molecules encoding for Gag, Rev, Vpr, and Nef from the patient’s autologous virus and loads them into dendritic cells (DC). Methods This phase IIB, multicenter, 2:1 randomized, double blind, placebo-controlled study enrolled 54 HIV-1-infected patients on antiretroviral therapy (ART) with viral loads (VL) <50 copies/mL, current CD4 T-cell counts >450 cells/mm3, and nadir counts >200 cells/mm3, to receive intradermal injections of study product into the axillary lymph node region every 4 weeks. At week 16, a 12-week analytical treatment interruption (ATI) was undertaken. Results There was no difference in the end-of-ATI VL (average of values from weeks 11 and 12) between the two arms of the study (4.39 [4.17, 4.69] vs. 4.47 [3.76, 4.64] log10 HIV-1 RNA; P = 0.73). Between arms no change between pre-ART VL and the end-of-ATI VL (−0.06 [0.24, −0.32] vs. −0.17 [0.17, −0.32] log10 HIV-1 RNA; P = 0.43) was observed. When IFN-γ, IL-2, TNF-α, CD107a, and granzyme b expression was measured by multicolor flow cytometry, a greater percentage of AGS-004 than of placebo recipients had multifunctional CTL responses induced in the CD28+/CD45RA-CD8 effector/memory T-cell population to DCs electroporated with autologous antigens. Adverse events consisted of transient, mild (grade 1) local injection site reactions. Conclusions Despite the induction of HIV-specific effector/memory CD8 T-cell responses, no antiviral effect was seen after the administration of AGS-004 when compared to placebo.