Impact of Insurance Status on Outcomes in Patients with AIDS-Defining Cancers

Background: Mortality among people living with the human immunodeficiency virus (PLWH [HIV]) diagnosed with acquired immunodeficiency syndrome (AIDS)-defining cancers has greatly decreased with the advent of highly active antiretroviral therapy (HAART). Recent investigations exploring the impact of insurance coverage have concluded that PLWH with public insurance have greater mortality than their privately insured counterparts. One avenue to augment medical coverage is the Ryan White HIV/AIDS Program, first authorized by Congress in 1990 to provide primary care and support services to PLWH. This study sets out to elucidate whether insurance coverage and Ryan White assistance affect treatment parameters and survival rates in PLWH diagnosed with Kaposi sarcoma (KS) and non-Hodgkin lymphomas (NHL). Methods: This was a retrospective cohort study of PLWH diagnosed with KS or NHL between 2004 and 2018. Baseline characteristics including demographics, insurance coverage, Ryan White assistance, CD4+ T-cell counts, HIV viral load, HAART treatment, performance status, and disease stage were collected. Participants were classified as having private insurance, Medicare, Medicaid, or no insurance. Treatment regimens were assessed as "optimal" or "suboptimal" using the National Comprehensive Cancer Network guidelines for AIDS-related KS and lymphomas as benchmark. Hazard ratios (HR) for survival were calculated using Cox proportional hazards regression models. Results: Among 191 participants with AIDS-defining cancers, 107 had KS, and 96 had aggressive NHL. 18% had private insurance, 14% had Medicare, 46% had Medicaid, and 23% had no health insurance; 44% received Ryan White assistance. Participants with Medicare and those without Ryan White assistance were older. Those with Ryan White assistance also had better performance status (defined as having an Eastern Cooperative Oncology Group score of 0 to 2). There were no significant differences in CD4+ T-cell counts, HIV viral loads, HAART adherence, treatment delays, regimen selection, and response rates across the insurance and Ryan White groups. The median treatment delay for all participants was 20 days. In general, participants with Medicare had lower overall survival than privately insured participants (HR 2.99, 95% confidence interval [CI] 1.14-7.87, p = 0.027). Participants without Ryan White assistance also had lower overall survival (HR 2.82, 95% CI 1.49-5.35, p = 0.002) and progression-free survival (HR 2.56, 95% CI 1.47-4.44, p < 0.001) than those with assistance. Other factors that influenced overall survival were age (adjusted HR 1.04 per year of age; 95% CI 1.01-1.06; p = 0.007), Hispanic ethnicity (adjusted HR 0.46 compared to Whites; 95% CI 0.24-0.91; p = 0.025), and poor performance status (adjusted HR 6.14; 95% CI 3.39-11.12; p < 0.00001). Conclusions: Our study is among the first to examine the impact of insurance coverage on outcomes in AIDS-defining malignancies. We find that PLWH with Medicare and those not receiving Ryan White assistance have lower survival. These differences may be ascribed in part to discrepancies in age, performance status, and prevalence of AIDS- and non-AIDS-related comorbidities. Reassuringly, our analysis suggests Ryan White assistance, despite its coverage limitations, is not associated with increases in treatment delays or suboptimal regimens. Nevertheless, the importance of dedicated care for this population at a multidisciplinary HIV/AIDS and comprehensive cancer center should not be undervalued. Future research should focus on whether the observed differences can be more broadly replicated in the United States. Figure Disclosures No relevant conflicts of interest to declare.

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The Impact of Cirrhosis on CD4+ T Cell Counts in HIV-Seronegative Patients

Clinical Infectious Diseases ◽

10.1086/509580 ◽

2007 ◽

Vol 44 (3) ◽

pp. 431-437 ◽

Cited By ~ 81

Author(s):

B. H. McGovern ◽

Y. Golan ◽

M. Lopez ◽

D. Pratt ◽

A. Lawton ◽

...

Keyword(s):

T Cell ◽

Cd4 T Cell ◽

Cell Counts ◽

The Impact

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The impact of diabetes on CD4 recovery in persons with HIV in an urban clinic in the United States

International Journal of STD & AIDS ◽

10.1177/0956462417717650 ◽

2017 ◽

Vol 29 (1) ◽

pp. 63-71 ◽

Cited By ~ 1

Author(s):

Julie A Zuniga ◽

Kirk A Easley ◽

Neeta Shenvi ◽

Minh L Nguyen ◽

Marcia Holstad

Keyword(s):

African American ◽

T Cell ◽

Cell Count ◽

African American Women ◽

Cd4 T Cell ◽

Cd4 Cell Count ◽

Cell Counts ◽

Cd4 Cell ◽

The Impact ◽

Cd4 T Cell Count

The purpose of this study was to exam the impact of type 2 diabetes mellitus (T2DM) on CD4 cell count trends in adults with HIV. In a longitudinal retrospective study in an urban primary care HIV clinic in the southeastern United States from 2010 to 2012, patients with HIV medical charts were audited to obtain their CD4 cell count, diabetes status, weight, and demographic information. Rates of increase of CD4 T cell count (i.e. slopes) were obtained using a linear mixed-effects model. Most of the HIV–T2DM cohort (n = 262) and HIV-only cohort (n = 2399) were African American (76%) and male (77%). The CD4 T cell counts were consistently higher in the HIV–T2DM cohort ( p < .0001). The mean rate of CD4 T cell count increase (mean ± SE) was 63 ± 9 cells/µl/year in HIV–T2DM African American women and 28 ± 7 cells/µl/year in HIV–T2DM African American men ( p = 0.003). In the multivariable slope analysis, the CD4 T cell count increase was significantly faster for HIV–T2DM African American women than for all other patients (mean difference = 30/cells/µl/year, 95% CI: 13–47; p < 0.001). Gender, race/ethnicity, and the diagnosis of diabetes influenced the recovery of CD4 cell counts.

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SARS-CoV-2 Humoral and Cellular Immune Responses in COVID-19 Convalescent Individuals With HIV

10.21203/rs.3.rs-1229520/v1 ◽

2022 ◽

Author(s):

Denise Giannone ◽

Maria Belén Vecchione ◽

Alejandro Czernikier ◽

Maria Laura Polo ◽

Virginia Gonzalez Polo ◽

...

Keyword(s):

T Cell ◽

Cellular Responses ◽

Antibody Responses ◽

Cd4 T Cell ◽

Neutralization Capacity ◽

Cytokines And Chemokines ◽

Cell Counts ◽

Hla Dr ◽

Ifn Γ ◽

The Impact

Abstract Background SARS-CoV-2-specific immune response features in people with HIV infection (PWH) remain to be fully elucidated. We aimed to evaluate the impact of HIV over humoral and cellular responses in COVID-19 convalescent PWH. Methods Blood samples from 29 PWH with preserved CD4+T-cell counts on ART and 29 HIV-negative (HIVneg) donors were included. SARS-CoV-2-specific IgG levels and IgG titers were determined by ELISA. Antibody neutralization capacity was evaluated against the reference B1 strain SARS-CoV-2. IFN-γ-secreting cells were detected by ELISpot using SARS-CoV-2 Spike, RBD, or Nucleocapsid protein or overlapping peptide pools. Frequency and phenotype of T, B and NK cells and levels of soluble cytokines and chemokines were assessed by flow cytometry. Results SARS-CoV-2-specific antibodies were detected on 65.5% of PWH and 79.3% of HIVneg individuals, with no differences in serum IgG levels and anti-SARS-CoV-2 neutralizing antibodies. All donors exhibited SARS-CoV-2-specific cellular immunity, including those with undetectable antibody responses. PWH showed diminished percentages of antibody-secreting cells compared to HIVneg cohort, with similar B cell proportions between groups. PWH presented an increment in T follicular helper (Tfh, CD4+CXCR5+) percentage, which negatively correlated with IgG titers. Additionally, CD4+PD1+ and CD8+HLA-DR+ cell frequencies were augmented in PWH. Moreover, PWH presented a high proportion of CD95+, CD25+, NKp46+, HLA-DR+, and CD38+/HLA-DR+ NK cells. Both groups displayed similar Tregs frequency, effector/memory, and T-helper profile for CD4TL, exhaustion and memory phenotypes for CD8TL and subtle differences in classical monocytes. Profile of circulating cytokines and chemokines was significantly different between both groups. Magnitude of IFN-γ responses to S or N proteins, and RBD was lower in PWH compared to HIVneg donors. Correlation analysis of immune and clinical parameters showed a distinct immune landscape in the PWH group. Conclusions PWH showed a distinctive immune profile although severity of COVID-19 was not exacerbated. PWH with conserved CD4+T-cell counts exerted both humoral and cellular responses against SARS-CoV-2. Even though cellular response was lower compared to HIVneg individuals, PWH achieved similar antibody responses with a high neutralization capacity. These data reinforce the impact of ART, not only in controlling HIV but also other infections.

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An Accelerated CD8+, but Not CD4+, T-Cell Reconstitution Associates with a More Favorable Outcome Following HLA-Haploidentical HSCT: Results from a Retrospective Study of the Cell Therapy and Immunobiology Working Party of the EBMT

Blood ◽

10.1182/blood.v126.23.1929.1929 ◽

2015 ◽

Vol 126 (23) ◽

pp. 1929-1929

Author(s):

Attilio Bondanza ◽

Loredana Ruggeri ◽

Dimitris Ziagkos ◽

Chiara Bonini ◽

Christian Chabannon ◽

...

Keyword(s):

Overall Survival ◽

T Cells ◽

T Cell ◽

Cd8 T Cells ◽

Immune Reconstitution ◽

Immune Cell ◽

Cd4 T Cell ◽

Cd4 Counts ◽

Cell Counts ◽

T Cell Reconstitution

Abstract Introduction and Aim: HLA-haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is increasingly offered to patients with high-risk acute myeloid (AML) or lymphoid leukemia (ALL). Unfortunately, graft manipulation employed to overcome the HLA barrier significantly delays immune reconstitution, posing the patients at risk of infections. Accordingly, non-relapse mortality after haplo-HSCT clearly extends beyond day 100 post-transplant. Over the years, different approaches have been investigated to speed-up immune reconstitution. In the absence of validated immune biomarkers, it is however difficult to evaluate the clinical impact of accelerated immune reconstitution. The aim of this EBMT retrospective study is to explore immune-cell counts early after haplo-HSCT as predictive of its overall outcome. Methods and Patients: Among AML and ALL patients in the EBMT database who underwent haplo-HSCT in the period 2001-2012, criteria for study entry were survival beyond day 100 and availability of differential immune-cell counts (CD3+, CD4+, CD8+ T cells, CD19+ B cells, CD16+/CD56+ NK cells) within this period. Accordingly, statistical analysis was landmarked at day 100. Of 259 patients meeting these criteria (age 2-70, median 33), 67 (26%) were children. The underlying disease was AML in 162 cases (63%), while ALL in the remaining (including 5 cases of bi-phenotypic leukemia). Fifty-two percent of patients were transplanted in CR1. The stem-cell source was G-CSF mobilized peripheral blood in all but one patient (>99%) and 171 received TBI (66%). The graft was manipulated in 199 patients (78%), including CD34-selection (50%), ex vivo T-cell depletion (15%) or both (13%). Female-to-male transplants were 68 (26%), while 204 (79%) recipients were CMV seropositive. Sustained hematopoietic engraftment was reached in 246 patients (95%) Results: The estimated overall survival at 2yrs was43%. The estimated cumulative incidence of death due to relapse was 33%, while that of death due to other causes was 35% (51% of those were infections) The occurrence of grade III-IV GVHD and of chronic GVHD was 9% and 18% (7% extensive), respectively. As expected, overall survival was better in children (62% vs 36%, P=0.002 by Log-rank), who clearly had a lower incidence of death due to causes other than relapse compared with adults (10% vs 37%, P=0.0001). Negative prognostic factors for overall survival were any disease state other than CR1 at time of transplantation (P=0.002) and CMV seropositivity (P=0.009). Type of leukemia, TBI or graft manipulation had no effect on the outcome. By day 100 post-transplant, patients reached the following median immune-cell counts: 100 CD3+ T cells (range 0-2576), 30 CD4+ T cells (0-1714), 48 CD8+ T cells (0-1880), 276 CD16+/CD56+ NK cells (18-3581), 21 CD19+ B cells (0-790). Importantly, CD3+ counts above the first quartile (1Q) of the entire data set (29 cells per microL) were significantly associated with a better overall survival (P=0.0005 by Log rank) and a lower incidence of death due to causes other than relapse (P=0.002 by Gray test). The same held true for CD8+ counts (1Q: 15 cells per microL; P=0.003 on overall survival; P=0.0004 on death due to other causes). CD4+ counts also showed similar correlations, but at higher values (above the median). None of the other immune-cell counts analyzed correlated with clinical outcome. Strikingly, when challenged in multivariate analysis taking into account age category, CMV seropositivity, graft manipulation and CR1 status at transplant, CD3+ and CD8+ counts above the 1Q adjusted to fit optimal cut-off points were still significantly associated with a better overall survival (P=0.006 and P=0.015, respectively), but only CD8+ values associated with a lesser risk of death due to causes other than relapse (P=0.026). Conversely, similarly adjusted median CD4+ counts failed to show any association. Conclusions: Contrary to what is generally accepted, these results indicate that an accelerated CD8+, but not CD4+, T cell reconstitution associates with a more favorable clinical outcome after haplo-HSCT, likely due to its protective role against opportunistic viral infections. Moreover, they suggest that yet to be validated CD8+ cut-off points, rather than the commonly used arbitrary value of 200 CD4+ T cells per microL, should be considered as surrogate biomarkers in clinical trials. Disclosures Bonini: MolMed S.p.A: Consultancy.

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Long-Term Consequences of Hepatitis C Viral Clearance on the CD4 (+) T Cell Lymphocyte Course in HIV/HCV Coinfected Patients

AIDS Research and Treatment ◽

10.1155/2015/687629 ◽

2015 ◽

Vol 2015 ◽

pp. 1-4 ◽

Cited By ~ 1

Author(s):

J. Dazley ◽

R. Sison ◽

J. Slim

Keyword(s):

Treatment Outcome ◽

Hepatitis C ◽

T Cell ◽

Linear Regression Analysis ◽

Cd4 T Cell ◽

Hcv Rna ◽

Cell Counts ◽

Pegylated Interferon Plus Ribavirin ◽

The Impact

The long-term impact of pegylated-interferon plus ribavirin treatment outcome on CD4 T cell course in patients coinfected with human immunodeficiency virus and hepatitis C virus is largely unclear in the literature. The aim of this study was to investigate the impact of HCV-RNA clearance by standard anti-HCV therapy on long-term CD4 cells recovery in HIV/HCV patients on successful combined antiretroviral therapy. We retrospectively enrolled HIV/HCV-coinfected patients on HIV medications and treated for hepatitis C. CD4 + T cell counts were registered at baseline and after hepatitis C therapy. Multiple linear regression analysis was performed to identify independent predictors of CD4 + T cell change following the anti-HCV treatment outcome. Of the 116 patients enrolled, 54 (46.6%) reached a sustained virological response. During a follow-up of 24 months, the SVR group showed a mean annual increase in CD4 + T cell from baseline of 84 cells/ll at 1 year and of a further 38 cells/ll within the second year (P=0.01, 0.001, resp.). An insignificant mean increase of 77 cells/ll occurred in the non-SVR group within month 24 (P=0.06). Variables associated with greater CD4 gains were higher nadir, lower preinterferon CD4 counts, and lower body mass index (BMI).

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Faculty Opinions recommendation of Low nadir CD4+ T-cell counts predict gut dysbiosis in HIV-1 infection.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.733930398.793561280 ◽

2019 ◽

Author(s):

Alan Landay

Keyword(s):

T Cell ◽

Cd4 T Cell ◽

Gut Dysbiosis ◽

Cell Counts ◽

Hiv 1

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The Impact of Exercise Serum on Selected Parameters of CD4+ T Cell Metabolism

Immuno ◽

10.3390/immuno1030008 ◽

2021 ◽

Vol 1 (3) ◽

pp. 119-131

Author(s):

Jana Palmowski ◽

Kristina Gebhardt ◽

Thomas Reichel ◽

Torsten Frech ◽

Robert Ringseis ◽

...

Keyword(s):

T Cells ◽

Oxygen Consumption ◽

T Cell ◽

Real Time ◽

Cd4 T Cells ◽

Cell Metabolism ◽

Cd4 T Cell ◽

Autologous Serum ◽

Cell Phenotype ◽

The Impact

CD4+ T cells are sensitive to peripheral changes of cytokine levels and metabolic substrates such as glucose and lactate. This study aimed to analyze whether factors released after exercise alter parameters of human T cell metabolism, specifically glycolysis and oxidative phosphorylation. We used primary human CD4+ T cells activated in the presence of autologous serum, which was collected before (CO) and after a 30-min exercise intervention (EX). In the course of activation, cells and supernatants were analyzed for cell viability and diameter, real-time oxygen consumption by using PreSens Technology, mRNA expression of glycolytic enzymes and complexes of the electron transport chain by real-time PCR, glucose, and lactate levels in supernatants, and in vitro differentiation by flow cytometry. EX did not alter T cell phenotype, viability, or on-blast formation. Similarly, no difference between CO and EX were found for CD4+ T cell activation and cellular oxygen consumption. In contrast, higher levels of glucose were found after 48 h activation in EX conditions. T cells activated in autologous exercise serum expressed lower HK1 mRNA and higher IFN-γ receptor 1. We suggest that the exercise protocol used was not sufficient to destabilize the immune metabolism of T cells. Therefore, more intense and prolonged exercise should be used in future studies.

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Lymphocyte subset analysis to evaluate the prognosis of HIV-negative patients with pneumocystis pneumonia

BMC Infectious Diseases ◽

10.1186/s12879-021-06124-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Fan Jin ◽

Jing Xie ◽

Huan-ling Wang

Keyword(s):

T Cell ◽

Cell Count ◽

Lymphocyte Subsets ◽

Nk Cell ◽

Cd8 T Cell ◽

Pneumocystis Pneumonia ◽

Lymphocyte Subset ◽

Cd4 T Cell ◽

Cell Counts ◽

Hiv Negative

Abstract Objectives We analysed the peripheral blood lymphocyte subsets of human immunodeficiency virus (HIV)-negative patients infected with pneumocystis pneumonia (PCP) to determine the relationships between the levels of different types of lymphocytes and the prognosis of patients. Methods We retrospectively reviewed HIV-negative patients with PCP diagnosed in our department. All the eligible patients underwent lymphocyte subset analysis on admission. Results A total of 88 HIV-negative PCP patients were enrolled in the study. In univariate analyses, low CD4+ T cell count, low CD8+ T cell count, and low natural killer cell (NK cell) count were associated with higher in-hospital mortality. CD8+ T cell count ≤300/μL was found to be an independent risk factor for poor prognosis in multivariate logistical regression analysis (p = 0.015, OR = 11.526, 95% CI = 1.597–83.158). Although low CD4+ T cell and NK cell counts were not independent risk factors, the mortality rates of PCP patients decreased as the CD4+ T cell and NK cell counts increased. Conclusion The immune process of Pneumocystis jirovecii infection is complex but important. We propose that lymphocyte subsets could give clinicians a better understanding of patient immune status, helping with the early identification of potentially lethal infections and treatment decision making, such as adjusting the immunosuppressive regimen and choosing an appropriate patient monitoring level.

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