Publications

Cytomegalovirus (CMV) is the most common viral infection in hematopoietic cell transplantation (HCT) recipients. We performed deep phenotyping of CMV-specific T cells to predict CMV outcomes following allogeneic HCT. By using 13-color flow cytometry, we studied ex vivo CD8 T-cell cytokine production in response to CMV-pp65 peptides in 3 clinically distinct subgroups of CMV-seropositive HCT patients: (1) (n = 19): did not have evidence of CMV DNAemia on surveillance testing; (2) (n = 16): spontaneously resolved low-grade CMV DNAemia without antiviral therapy; and (3) (NC; n = 21): experienced clinically significant CMV. Two CMV-specific CD8 T-cell functional subsets were strongly associated with risk of CMV: (i) the (NPS; IL-2IFN-γTNF-αMIP-1β), found at increased levels among NC; and (ii) the (PS; IL-2IFN-γTNF-αMIP-1β) found at low levels among NC. High levels of the NPS and low levels of PS were associated with an increased 100-day cumulative incidence of clinically significant CMV infection (35% vs 5%; = .02; and 40% vs 12%; = .05, respectively). The highest predictive value was observed when these signatures were combined into a composite biomarker consisting of low levels of the PS and high levels of the NPS (67% vs 10%; < .001). After adjusting for steroid use or donor type, this composite biomarker remained associated with a fivefold increase in the risk of clinically significant CMV infection. CMV-specific CD8 T-cell cytokine signatures with robust predictive value for risk of CMV reactivation should prove useful in guiding clinical decision making in HCT recipients.

We developed a nontargeted diabetes screening program in a rural Indian Health Service emergency department in Shiprock, New Mexico to measure the proportion of previously undiagnosed diabetes and prediabetes, and to assess glycemic control among patients with known disease. Of 924 patients screened in the emergency department between May and July 2017, 28.8% screened positive for previously undiagnosed diabetes or prediabetes; among patients with known disease, the median hemoglobin A1c was 8.2%. Of the newly identified patients, 54.9% attended follow-up.

BACKGROUND

In the US, the HIV diagnostic algorithm for laboratory settings recommends the use of an HIV-1/HIV-2 differentiation supplemental assay after an initial reactive antigen/antibody (Ag/Ab) assay result. Since the discontinuation of the Multispot HIV-1/HIV-2 Rapid Test (MS), the Geenius HIV-1/2 Supplemental assay (Geenius) is the only FDA-approved supplemental differentiation test.

OBJECTIVE

We compared the performance of Geenius to MS and Western Blot (WB).

STUDY DESIGN

The relative seroconversion plasma reactivity of Geenius and MS was assessed using a 50% cumulative frequency analysis from 17 HIV-1 seroconverters. In addition, previously characterized plasma specimens, 186 HIV-1 positive, 100 HIV-2 positive, and 93 Ag/Ab-positive/HIV-1 RNA-negative, were tested with Geenius v1.1 software. McNemar's test was used for paired comparison analysis. A subset of 48 specimens were retested with the upgraded Geenius v1.3 software.

RESULTS

In HIV-1 seroconverters, the relative seroconversion reactivity was 2.5 and 2 days before the first positive HIV-1 WB for Geenius and MS, respectively. In HIV-1 positive samples, Geenius performed similarly to HIV-1 WB (p=0.1687) and MS (p=0.8312). In HIV-2 positive samples, Geenius underperformed compared to HIV-2 WB (p=0.0005) and MS (p=0.0012). When using the upgraded software among the HIV-1 positive and Ag/Ab-reactive/HIV-1 RNA-negative samples, gp140 reactivity decreased without affecting characterization of HIV-2 samples.

CONCLUSIONS

With HIV-1 samples, Geenius, WB and MS performance was similar as supplemental tests. The updated Geenius software reduced false gp140 reactivity, but had no impact on identifying true HIV-2 infections. Further evaluation will assess the impact of the Geenius software update on final diagnostic interpretations.