ABSTRACT
Mosaic HIV-1 vaccines have been shown to elicit robust humoral and cellular immune responses in people living with HIV-1 (PLWH), that had started antiretroviral therapy (ART) during acute infection. We evaluated the safety and immunogenicity of 2 mosaic vaccine regimens in virologically suppressed individuals that had initiated ART during the chronic phase of infection, exemplifying the majority of PLWH. In this double-blind, placebo-controlled phase 1 trial (IPCAVD013/HTX1002) 25 ART-suppressed PLWH were randomized to receive Ad26.Mos4.HIV/MVA-Mosaic (Ad26/MVA) (n = 10) or Ad26.Mos4.HIV/Ad26.Mos4.HIV plus adjuvanted gp140 protein (Ad26/Ad26+gp140) (n = 9) or placebo (n = 6). Primary endpoints included safety and tolerability and secondary endpoints included HIV-specific binding and neutralizing antibody titers and HIV-specific T cell responses. Both vaccine regimens were well tolerated with pain/tenderness at the injection site and fatigue, myalgia/chills and headache as the most commonly reported solicited local and grade 3 systemic adverse events, respectively. In the Ad26/Ad26+gp140 group, Env-specific IFN-γ T cell responses showed a median 12-fold increase while responses to Gag and Pol increased 1.8 and 2.4-fold, respectively. The breadth of T cell responses to individual peptide subpools increased from 11.0 pre-vaccination to 26.0 in the Ad26/Ad26+gp140 group and from 10.0 to 14.5 in the Ad26/MVA group. Ad26/Ad26+gp140 vaccination increased binding antibody titers against vaccine-matched clade C Env 5.5-fold as well as augmented neutralizing antibody titers against Clade C pseudovirus by 7.2-fold. Both vaccine regimens were immunogenic, while the addition of the protein boost resulted in additional T cell and augmented binding and neutralizing antibody titers. These data suggest that the Ad26/Ad26+gp140 regimen should be tested further.
ABSTRACT
We aimed to analyze rates and risk factors for carbapenemase-producing Enterobacterales (CPE) bloodstream infection (BSI) in CPE-colonized patients with malignancies or following hematopoietic cell transplantation. We retrospectively collected data on demography, underlying disease, colonizing CPE, treatment, intensive care unit (ICU) hospitalization, CPE-BSI, and mortality in CPE-colonized immunocompromised patients (2014-2020). Two hundred twenty-one patients were colonized with 272 CPE: 254 (93.4%) carried one carbapenemase [KPC (50.4%), NDM (34.6%), OXA-48-like (5.2%), and VIM (3.3%)]; 18 (6.6%) carried two carbapenemases. Twenty-eight (12.7%) patients developed CPE-BSI. Univariate analysis revealed CPE-BSI-associated factors: younger age, carbapenem or aminoglycoside exposure, ICU admission, neutropenia, carrying serine carbapenemase-producing, and specifically KPC-producing bacteria, colonization with several CPE, and detection of several carbapenemases. None of 23 auto-HSCT recipients developed CPE-BSI. In multivariate analysis, ICU hospitalization was significantly associated with CPE-BSI (odds ratio [OR] 2.82, 95% CI 1.10-7.20; p = 0.042); solid tumor diagnosis was protective (OR 0.21, 95% CI 0.05-1.01; p = 0.038). One-year crude mortality was 108/221 (48.8%), including 19/28 (67.9%) and 89/193 (46.1%) in patients with and without CPE-BSI, p = 0.104. To conclude, CPE-BSI is rare in CPE-colonized patients with solid tumors and following auto-HSCT. ICU hospitalization increased CPE-BSI risk. These data can help to guide empirical anti-CPE antibiotic therapy in patients colonized with these bacteria.
