The latest medical research on Infectious Disease

The All of Us (AoU) Research Program is a national-scale effort to build a dataset to help transform the future of health research by equipping researchers with comprehensive health data from diverse populations, especially those underrepresented in biomedical research. Our objectives were to evaluate the burden of HIV and major depressive disorder (MDD) in underrepresented groups and the frequency of the HIV/MDD comorbidity.

We conducted a cross-sectional analysis combining collected survey and electronic health record (EHR) data. We ascertained HIV and MDD cases using Observational Medical Outcomes Partnership codes. We used multivariable logistic regression to obtain the odds ratio of HIV in AoU participants and MDD in AoU participants with HIV.

The latest AoU data release includes 412 211 participants: 254 700 have at least one medical condition concept in their EHR, of whom 5193 (1.3%) had HIV, and 2238 (43%) of those with HIV had a diagnosis of MDD. Black AoU participants had approximately 4.58 times the odds of having an HIV diagnosis compared with the combined odds of all other racial groups. AoU participants with HIV were more likely to have MDD (p = 0.001) than were participants without HIV.

Among AoU participants, Black individuals have a disproportionately high burden of HIV, pointing to underlying factors such as social determinants of health, limited access to healthcare or prevention resources, and potential systemic biases that contribute to these differences. In addition, HIV is a risk factor for mental health issues like MDD. Further data collection from people with HIV will elucidate contributing factors and the need for interventions.

Antiretroviral therapy (ART), which is increasingly used by people with HIV, accounts for significant care costs, particularly because of single-tablet regimens (STRs). This study explored de-simplification to a two-tablet regimen (TTR) for cost reduction. The objectives of this study were: (1) acceptance of de-simplification, (2) patient-reported outcomes, and (3) cost savings.

All individuals on Triumeq®, Atripla® or Eviplera® in five HIV clinics in the Netherlands were eligible. Healthcare providers informed individuals of this study. After inclusion, individuals were free to de-simplify. An electronic questionnaire was sent to assess study acceptance, adherence, quality of life (SF12) and treatment satisfaction (HIVTSQ). After 3 and 12 months, questionnaires were repeated. Cost savings were calculated using Dutch drug prices.

In total, 283 individuals were included, of whom 55.5% agreed to de-simplify their ART, with a large variability between treatment centres: 41.1-74.2%. Individuals who were willing to de-simplify tended to be older, had a longer history of HIV diagnosis, and used more co-medication than those who preferred to remain on an STR regimen. Patient-reported outcomes, including quality of life and treatment satisfaction, showed no significant difference between people with HIV who switched to a TTR and those who remained on an STR regimen. Furthermore, we observed a 17.8% reduction in drug costs in our cohort of people with HIV who were initially on an STR.

De-simplification from an STR to a TTR within the Dutch healthcare setting has been demonstrated as feasible, leads to significant cost reductions and should be discussed with every eligible person with HIV in the Netherlands.

Cytomegalovirus-specific T-cell-mediated immunity (CMV-CMI) protects from CMV infection in allogeneic hematopoietic cell transplantation (allo-HCT), but to date, there is no validated measure of CMV immunity for this population.

In this prospective, observational, pilot study, CMV T-cell responses were evaluated monthly and at onset of graft-versus-host disease (GVHD) or CMV infection in CMV-seropositive allo-HCT recipients using a commercial flow cytometry assay, the CMV inSIGHT T-Cell Immunity Panel (CMV-TCIP). The primary endpoint was the time to first positive CMV-TCIP, defined as percentage of interferon-γ-producing CD4+ or CD8+ CMV-specific T cells >0.2%. Letermovir was prescribed from day +10 to ≥100.

Twenty-eight allo-HCT recipients were enrolled. The median time to first positive CMV-TCIP result was earlier for CD4+ (60 days [interquartile range, IQR 33‒148]) than for CD8+ T cells (96 days [IQR 33‒155]) and longer for haploidentical and mismatched transplant recipients (77 and 96 days, respectively) than for matched donors (45 and 33 days, respectively). CD4+ and CD8+ CMV-CMI recovery was sustained in 10/10 (100%) and 10/11 (91%) patients, respectively, without GVHD, whereas CD4+ and/or CD8+ CMV-CMI was lost in 4/6 and 2/6 patients, respectively, with GVHD requiring steroids. As a predictor of clinically significant CMV infection in patients with low-level CMV reactivation, the sensitivity and negative predictive value of CMV-TCIP were 90% and 87.5%, respectively, for CD4+ CMV-TCIP and 66.7% and 62.5%, respectively, for CD8+ CMV-TCIP.

There was significant variability in time to CMV-CMI recovery post-HCT, with slower recovery after haploidentical and mismatched HCT. CD4+ CMV-CMI may protect against CS-CMVi, but immunity may be lost with GVHD diagnosis and treatment.