Rapid COVID-19 Testing of Symptomatic Health Care Personnel: A Strategy for Safely Maintaining the Workforce.

Objective: Determine performance characteristics and safety outcomes of two rapid COVID-19 screening methods to inform immediate return to work (RTW) decisions while health care personnel (HCP) await results of pending confirmatory laboratory test.

Methods: This is a retrospective, occupational health quality improvement study comparing screening with rapid SARS-CoV-2 nucleic acid amplification (NAAT) and antigen test.

Results: Five hundred thirty-one mildly symptomatic HCP screened over 16 months.

Risk of subsequent SARS-CoV-2 infection among vaccinated employees with or without hybrid immunity acquired early in the Omicron-predominant era of the COVID-19 pandemic.

Background: Hybrid immunity, from COVID-19 vaccination followed by SARS-CoV-2 infection acquired after its Omicron variant began predominating, has provided greater protection than vaccination alone against subsequent infection over 1-3 months of observation. Its longer-term protection is unknown.

Methods: We conducted a retrospective cohort study of COVID-19 case incidence among healthcare personnel (HCP) mandated to be vaccinated and report on COVID-19-associated symptoms, high-risk exposures, or known-positive test results to an employee health hotline.

A Rapid Nucleic Acid Amplification Test-Based, Conditional Release-to-Work Policy for Health Care Personnel With Symptoms Consistent With COVID-19.

Objective: Most health care personnel (HCP) reporting symptoms consistent with COVID-19 illness are assessed by high-accuracy SARS-CoV-2 assays performed in clinical laboratories, but the results of such assays typically are not available until the following day.

Methods: This is an observational study over 16 weeks of a rapid nucleic acid amplification test (NAAT) performed at point of contact. The benchmark for comparison was a simultaneously obtained specimen assayed by a routine NAAT assay performed in a clinical laboratory.

Temperature Screening of Healthcare Personnel Is Ineffective in Controlling COVID-19.

Objective: Our aim was to describe the effectiveness of employee temperature screening at a public hospital in San Francisco during the COVID-19 pandemic.

Methods: An estimated 6000 health care personnel (HCP) underwent daily screening before entry to campus. Logs of failed employee entrance temperature screenings from March 2020 through March 2021 were reviewed.

Incidence and Characteristics of Delayed Injection Site Reaction to the mRNA-1273 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccine (Moderna) in a Cohort of Hospital Employees.

Background: mRNA SARS-CoV-2 vaccines are administered to 2 million individuals per day in the United States under US Food and Drug Administration emergency use authorization.

Methods: Observational cohort study of hospital employees who received their first SARS-CoV-2 mRNA vaccination between 14 December 2020 and 8 January 2021, including employees who reported onset of an injection site reaction ≥48 hours after administration of their first or second dose to an employee hotline.

Results: Thirteen female employees who received the mRNA-1273 vaccine (Moderna) during the first 3 weeks of the SARS-CoV-2 vaccine rollout at San Francisco General Hospital reported a pruritic rash at the injection site appearing 3 -9 days after receipt of their initial dose.

Human papillomavirus infection in the oral cavity of HIV patients is not reduced by initiating antiretroviral therapy.

Objective: The incidence of human papillomavirus (HPV)-related oral malignancies is increasing among HIV-infected populations, and the prevalence of oral warts has reportedly increased among HIV patients receiving antiretroviral therapy (ART). We explored whether ART initiation among treatment-naive HIV-positive adults is followed by a change in oral HPV infection or the occurrence of oral warts.

Design: Prospective, observational study.

Regulatory T cells and the risk of CMV end-organ disease in patients with AIDS.

Objectives: Cytomegalovirus (CMV)-specific T-cell effectors (CMV-Teff) protect against CMV end-organ disease (EOD). In HIV-infected individuals, their numbers and function vary with CD4 cell numbers and HIV load. The role of regulatory T cells (Treg) in CMV-EOD has not been extensively studied.

The clinical impact of continuing to prescribe antiretroviral therapy in patients with advanced AIDS who manifest no virologic or immunologic benefit.

Introduction: Despite the efficacy and tolerability of modern antiretroviral therapy (ART), many patients with advanced AIDS prescribed these regimens do not achieve viral suppression or immune reconstitution as a result of poor adherence, drug resistance, or both. The clinical outcomes of continued ART prescription for such patients have not been well characterized.

Methods: We examined the causes and predictors of all-cause mortality, AIDS-defining conditions, and serious non-AIDS-defining events among a cohort of participants in a clinical trial of pre-emptive therapy for CMV disease.

Valganciclovir reduces T cell activation in HIV-infected individuals with incomplete CD4+ T cell recovery on antiretroviral therapy.

Background: Elevated immune activation persists during treated human immunodeficiency virus (HIV) infection and is associated with blunted CD4 recovery and premature mortality, but its causes remain incompletely characterized. We hypothesized that asymptomatic cytomegalovirus (CMV) replication might contribute to immune activation in this setting.

Methods: Thirty antiretroviral therapy-treated HIV-infected CMV-seropositive participants with CD4 counts <350 cells/mm(3) were randomized to receive valganciclovir 900 mg daily or placebo for 8 weeks, followed by an additional 4-week observation period.

Development of cytomegalovirus (CMV) immune recovery uveitis is associated with Th17 cell depletion and poor systemic CMV-specific T cell responses.

Background: the immune reconstitution inflammatory syndromes (IRIS) are a spectrum of inflammatory conditions associated with opportunistic infections and occurring in approximately16% of human immunodeficiency type 1 (HIV-1)-infected patients given antiretroviral therapy. It has been proposed that these conditions are linked by a dysregulated immune system that is prone to exaggerated responses. However, immunologic studies have been limited by the availability of longitudinal samples from patients with IRIS and appropriate matched control subjects.

Human herpesvirus replication and abnormal CD8+ T cell activation and low CD4+ T cell counts in antiretroviral-suppressed HIV-infected patients.

Background: Most HIV-infected patients receiving virologically suppressive antiretroviral therapy continue to have abnormal, generalized T cell activation. We explored whether the degree of ongoing cytomegalovirus (CMV), Epstein-Barr virus (EBV) and Kaposi's sarcoma herpesvirus (KSHV) replication was associated with higher virus-specific T cell activation and the failure to achieve normal absolute CD4+ T cell counts in the face of long-term suppressive antiretroviral therapy.

Methodology: Longitudinally collected PBMC and saliva specimens obtained from HIV-infected patients on effective antiretroviral therapy for at least one year (plasma HIV RNA <75 copies/mL) were examined using a multiplex CMV, EBV and KSHV DNA PCR assay.

A CMV DNA vaccine primes for memory immune responses to live-attenuated CMV (Towne strain).

CMV-seronegative subjects vaccinated intramuscularly or intradermally with a DNA vaccine encoding pp65, IE1, and gB were administered live-attenuated CMV (Towne) to characterize immune priming by the DNA vaccine. CMV-specific memory T-cells (detected by standard ELISPOT assay in only 20% of subjects) were detected by IFN-gamma cultured ELISPOT assay in 60% of subjects primed intramuscularly and correlated with immune responses after Towne. The median time to first pp65 T-cell and gB antibody response after Towne was 14 days for DNA-primed subjects vs.

Poor predictive value of cytomegalovirus (CMV)-specific T cell assays for the development of CMV retinitis in patients with AIDS.

Background: We examined the potential clinical utility of using a cytomegalovirus (CMV)-specific T cell immunoassay to determine the risk of developing new-onset CMV retinitis (CMVR) in patients with acquired immunodeficiency syndrome (AIDS).

Methods: CMV-specific T cell assays were performed by multiparameter flow cytometry using stored peripheral blood mononuclear cells that had been obtained in an observational study 2-6 months before new-onset CMVR was diagnosed in case patients (at a study visit during which a dilated ophthalmologic examination revealed no evidence of CMVR) and at the same study visit in control subjects (matched by absolute CD4(+) T cell count at entry) who did not subsequently develop retinitis during 1-6 years of study follow-up.

Results: There were no significant differences in CMV-specific CD4(+) or CD8(+) T cell interferon-gamma or interleukin-2 expression in peripheral blood mononuclear cells from case patients and control subjects.

Loss of T cell responses following long-term cryopreservation.

Although cryopreservation of peripheral blood mononuclear cells (PBMC) is a commonly used technique, the degree to which it affects subsequent functional studies has not been well defined. Here we demonstrate that long-term cryopreservation has detrimental effects on T cell IFN-gamma responses in human immunodeficiency virus (HIV) infected individuals. Long-term cryopreservation caused marked decreases in CD4(+) T cell responses to whole proteins (HIV p55 and cytomegalovirus (CMV) lysate) and HIV peptides, and more limited decreases in CD8(+) T cell responses to whole proteins.

Effect of a four-week course of interleukin-10 on cytokine production in a placebo-controlled study of HIV-1-infected subjects.

Interleukin (IL)-10 suppresses synthesis of the pro-inflammatory cytokines tumor necrosis factor (TNF)alpha, IL-1beta, and interferon (IFN)gamma. Since pro-inflammatory cytokines have been implicated in the production of human immunodeficiency virus type 1 (HIV-1), cytokine synthesis in whole blood cultures were determined during a 4-week course of subcutaneous IL-10 injections in 33 HIV-1-infected patients. Patients were randomized into four groups: placebo (nine), IL-10 at 1 microg/kg/day (nine), IL-10 at 4 microg/kg/day (six) and IL-10 at 8 microg/kg three times per week (nine).

Do CD4+ T cell functional responses to Epstein-Barr virus provide protective immunity against CNS lymphoma in AIDS?

Jacobson discusses a new study addressing the question of whether an EBV antigen-specific T cell response might be a critical component of protective immunity that is lost as part of the pathogenesis of AIDS-related primary CNS lymphoma.

Protective immunity to cytomegalovirus (CMV) retinitis in AIDS is associated with CMV-specific T cells that express interferon- gamma and interleukin-2 and have a CD8+ cell early maturational phenotype.

To determine potential correlates of immune recovery from AIDS-related cytomegalovirus retinitis (CMVR), multiparameter flow cytometry was used to characterize CMV-specific T cells from subjects with CMVR. Individuals with active retinitis were compared with those who had been clinically immunorestored by antiretroviral therapy and had > or =2 years of ophthalmologic follow-up without anti-CMV therapy or retinitis reactivation or progression. In comparison with patients with active retinitis, immunorestored patients had higher circulating CD4(+) and CD8(+) T cells expressing interleukin-2 and interferon- gamma in response to combined CMV pp65 and IE1 peptide pool stimulation.

Safety and immunogenicity of Towne cytomegalovirus vaccine with or without adjuvant recombinant interleukin-12.

The Towne, human cytomegalovirus (CMV) vaccine is safe and immunogenic but has not prevented infection at doses tested to date. We administered 3000 pfu Towne CMV vaccine, with or without adjuvant recombinant interleukin-12 (rhIL-12), to CMV-seronegative healthy volunteers and then measured CMV gB-specific IgG titers and CMV-specific CD4+ and CD8+ T cell proliferation and IFNgamma expression after stimulation with whole viral lysate and immunodominant peptide CMV antigens. Adjuvant rhIL-12 at doses up to 2 microg were well-tolerated and associated with (1) dose-related increases in peak anti-CMV gB IgG titers (though not in sustained titers), (2) dose-related increases in the weak CMV viral lysate-specific CD4+ T cell proliferation responses induced by vaccine alone after 360 days of follow-up, and (3) decreases in the very robust CMV IE-specific peak CD4+ T cell and Day 360 CD8+ T cell proliferation responses induced by the vaccine alone.

Antigen-specific T cell responses induced by Towne cytomegalovirus (CMV) vaccine in CMV-seronegative vaccine recipients.

Background: Towne cytomegalovirus (CMV) vaccine is safe and immunogenic, though its protective efficacy has yet to be optimized.

Objective: Describe antigen-specific T cell responses to Towne vaccination.

Study Design: 3000 pfu Towne CMV vaccine were given to 12 CMV-seronegative volunteers.

Pharmacokinetics of clarithromycin extended-release (ER) tablets in patients with AIDS.

Background: Clarithromycin is a key agent in effective antimycobacterial therapy and prophylaxis for AIDS-related disseminated Mycobacterium avium complex (dMAC) infection. Immediate-release (IR) clarithromycin tablets are dosed at 500 mg bid for these indications. A new extended-release (ER) tablet of clarithromycin has been developed and approved at a dosing interval of once every 24 hours for treatment of respiratory tract bacterial infections.

Risk factors for mortality in patients with AIDS in the era of highly active antiretroviral therapy.

Objective: To evaluate risk factors for mortality among patients with AIDS in the era of highly active antiretroviral therapy (HAART), particularly the effect of cytomegalovirus (CMV).

Design: Prospective cohort study of patients with AIDS, conducted from 1998 through 2003.

Participants: One thousand five hundred eighty-three patients with AIDS, of whom 374 had CMV retinitis.

Lower CD4+ T lymphocyte nadirs may indicate limited immune reconstitution in HIV-1 infected individuals on potent antiretroviral therapy: analysis of immunophenotypic marker results of AACTG 5067.

Background: Although initiation of potent antiretroviral therapy (ART) has significantly improved immune perturbations in individuals with AIDS, it is unclear which factors are most important in determining the degree of immune reconstitution.

Methods: Whole blood was analyzed at baseline and week 12 in six groups of subjects (n = 81): those with acute or following immune reconstitution after Pneumocystis jirovecii (previously known as Pneumocystis carinii) pneumonia (PcP) (two groups) and cytomegalovirus (CMV) retinitis (two groups), HIV-infection without AIDS (one group), and healthy volunteers (one group). Absolute CD4+ and CD8+ T lymphocytes, naive (CD45RA+) and memory (CD45RO+) CD4+ T lymphocytes and percentages of activated CD8+ T lymphocytes (CD8+/CD38+/HLA-DR), and CD28 expression on CD4+ and CD8+ T lymphocytes were enumerated.