Programmed Cell Death Protein 1 (PD-1) Signaling in HIV-Associated Cardiovascular Disease: Mechanisms and Therapeutic Implications

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Programmed Cell Death Protein 1 (PD-1) Signaling in HIV-Associated

Cardiovascular Disease: Mechanisms and Therapeutic Implications
Article · April 2024
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Elite Journal of Scientific Research and Review. Volume 2 issue 2(2024), Pp. 61-77
https://epjournals.com/journals/EJSRR
Programmed Cell Death Protein 1 (PD-1) Signaling in HIV-Associated Cardiovascular

Disease: Mechanisms and Therapeutic Implications
*
Emmanuel Ifeanyi Obeagu1 and Getrude Uzoma Obeagu2
1
Department of Medical Laboratory Science, Kampala International University, Uganda
2
School of Nursing Science, Kampala International University, Uganda
*
Corresponding authour: Emmanuel Ifeanyi Obeagu, Department of Medical Laboratory Science,
Kampala International University, Uganda, [email protected], ORCID: 0000-0002-
4538-0161
Abstract
Cardiovascular disease (CVD) remains a significant cause of morbidity and mortality in

individuals living with HIV/AIDS, despite effective antiretroviral therapy (ART). Emerging
evidence suggests a complex interplay between chronic inflammation, immune dysregulation, and
endothelial dysfunction in the pathogenesis of HIV-associated CVD. The programmed cell death
protein 1 (PD-1) pathway, known for its role in regulating immune responses and maintaining
immune homeostasis, has recently garnered attention for its potential involvement in HIV-
associated cardiovascular complications. This review provides a comprehensive overview of the
current understanding of PD-1 signaling in HIV-associated CVD, elucidating its mechanistic
contributions to vascular inflammation, endothelial dysfunction, atherosclerosis, and myocardial
injury. Furthermore, we discuss the therapeutic implications of targeting the PD-1 pathway as a
novel therapeutic strategy for mitigating cardiovascular risk in individuals living with HIV/AIDS.
Keywords: Programmed Cell Death Protein 1 (PD-1), HIV, cardiovascular disease, inflammation,
immune dysregulation, immune checkpoint inhibitors, therapeutic targets
Introduction
Cardiovascular disease (CVD) remains a significant cause of morbidity and mortality among
individuals living with HIV/AIDS, despite the remarkable advancements in antiretroviral therapy
(ART). While ART has significantly improved the life expectancy of HIV-infected individuals,
they continue to face a disproportionately high risk of developing CVD compared to the general
population. This increased cardiovascular risk is multifactorial and encompasses traditional risk
Citation: Obeagu EI, Obeagu, GU. Programmed Cell Death Protein 1 (PD-1) Signaling in HIV-
Associated Cardiovascular Disease: Mechanisms and Therapeutic Implications. Elite Journal of
Scientific Research and Review, 2024; 2(1): 61-77
1
factors, such as hypertension, dyslipidemia, and smoking, as well as HIV-specific factors,

including chronic inflammation, immune dysregulation, and direct viral effects on the vasculature.
Emerging evidence suggests that immune checkpoint pathways, particularly the programmed cell
death protein 1 (PD-1) pathway, may play a crucial role in the pathogenesis of HIV-associated
CVD. PD-1, a coinhibitory receptor expressed on activated T cells, regulates immune responses
by inhibiting T-cell activation and effector functions, thereby maintaining immune tolerance and
preventing autoimmunity. Dysregulated PD-1 signaling in the setting of chronic HIV infection
leads to persistent immune activation and inflammation, which have been implicated in the
development and progression of cardiovascular complications.1-20
The role of PD-1 signaling in vascular inflammation and endothelial dysfunction is of particular
interest in the context of HIV-associated CVD. Chronic immune activation and inflammation
contribute to endothelial dysfunction, characterized by impaired endothelium-dependent
vasodilation, increased expression of adhesion molecules, and enhanced endothelial permeability.
PD-1-expressing T cells accumulate within the vascular microenvironment, where they interact
with endothelial cells and perpetuate vascular inflammation through the production of pro-
inflammatory cytokines and chemokines, as well as the induction of oxidative stress.
Atherosclerosis, a chronic inflammatory disease of the arterial wall characterized by the
accumulation of lipid-rich plaques, is a major contributor to CVD in HIV-infected individuals.
PD-1 signaling influences the development and progression of atherosclerosis by modulating
immune cell recruitment, foam cell formation, and plaque stability. PD-1-expressing T cells within
atherosclerotic plaques exhibit a pro-inflammatory phenotype, contributing to plaque vulnerability
and the risk of acute cardiovascular events. Furthermore, PD-1 signaling may play a role in
myocardial injury in HIV-infected individuals, potentially contributing to the development of
myocarditis, cardiomyopathy, and heart failure. Given the growing recognition of the role of PD-
1 signaling in HIV-associated CVD, there is increasing interest in exploring the therapeutic
implications of targeting the PD-1 pathway as a novel approach to mitigate cardiovascular risk in
this population. Immune checkpoint inhibitors, such as PD-1 blockade, have shown efficacy in
attenuating vascular inflammation, improving endothelial function, and reducing atherosclerotic
burden in preclinical models and clinical studies of other inflammatory diseases. Understanding
the specific role of PD-1 signaling in HIV-associated CVD and elucidating the mechanisms
underlying its contribution to cardiovascular pathology may pave the way for the development of
innovative therapeutic strategies to improve cardiovascular outcomes in individuals living with
HIV/AIDS.21-55
PD-1 Signaling in Vascular Inflammation and Endothelial Dysfunction
PD-1 signaling plays a pivotal role in modulating vascular inflammation and endothelial
dysfunction, both of which are central to the pathogenesis of HIV-associated cardiovascular
disease (CVD). Chronic immune activation and inflammation, characteristic features of HIV
infection, contribute to endothelial dysfunction, a critical early event in the development of
atherosclerosis and other cardiovascular complications. PD-1-expressing T cells are key mediators
of vascular inflammation, as they accumulate within the vascular microenvironment and interact
2
with endothelial cells, perpetuating an inflammatory cascade. Within the context of HIV infection,
dysregulated PD-1 signaling leads to persistent immune activation and inflammation, further
exacerbating endothelial dysfunction. PD-1-expressing T cells exhibit an activated phenotype and
produce pro-inflammatory cytokines and chemokines that promote endothelial cell activation and
dysfunction. Additionally, PD-1 signaling inhibits T-cell proliferation and effector functions,
impairing the clearance of pathogens and damaged cells, which can further contribute to vascular
inflammation and endothelial injury.56-86
Endothelial dysfunction is characterized by impaired endothelium-dependent vasodilation,

increased expression of adhesion molecules, and enhanced endothelial permeability, all of which
promote vascular inflammation and atherosclerosis. PD-1 signaling influences endothelial
function by regulating the production of nitric oxide (NO), a key mediator of vasodilation, and the
expression of adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1) and
intercellular adhesion molecule-1 (ICAM-1), which facilitate leukocyte recruitment and adhesion
to the endothelium. In addition to its effects on endothelial cells, PD-1 signaling impacts other cell
types within the vascular microenvironment, including macrophages and smooth muscle cells,
further contributing to vascular inflammation and atherosclerosis. PD-1-expressing macrophages
exhibit an M1 pro-inflammatory phenotype and produce cytokines and chemokines that promote
plaque formation and progression. PD-1 signaling also regulates smooth muscle cell proliferation
and migration, key processes in the development of atherosclerotic lesions.87-107
Role of PD-1 Signaling in Atherosclerosis and Myocardial Injury
The programmed cell death protein 1 (PD-1) signaling pathway plays a crucial role in the
development and progression of atherosclerosis, a chronic inflammatory disease of the arterial wall
characterized by the accumulation of lipid-rich plaques. In the context of HIV infection,
dysregulated PD-1 signaling contributes to persistent immune activation and inflammation, which
are key drivers of atherosclerosis. PD-1-expressing T cells within atherosclerotic plaques exhibit
a pro-inflammatory phenotype, producing cytokines and chemokines that promote plaque
formation and progression. Furthermore, PD-1 signaling influences immune cell recruitment, foam
cell formation, and plaque stability, thereby impacting the overall vulnerability of atherosclerotic
lesions to rupture and thrombosis. PD-1 signaling regulates the balance between pro-inflammatory
and anti-inflammatory responses within atherosclerotic plaques, thereby influencing plaque
stability and the risk of acute cardiovascular events. PD-1-expressing T cells modulate the activity
of macrophages and other immune cells within plaques, promoting the production of matrix
metalloproteinases (MMPs) and other proteolytic enzymes that degrade the fibrous cap and
weaken plaque integrity. Additionally, PD-1 signaling influences the formation of foam cells,
lipid-laden macrophages that contribute to plaque progression and instability. In addition to its role
in atherosclerosis, PD-1 signaling may also contribute to myocardial injury in individuals living
with HIV/AIDS. Chronic immune activation and inflammation associated with HIV infection can
lead to myocarditis, cardiomyopathy, and heart failure, all of which are characterized by
myocardial inflammation, oxidative stress, and impaired contractile function. PD-1-expressing T
3
cells within the myocardium may exacerbate myocardial injury through their effects on
inflammation, fibrosis, and cardiomyocyte apoptosis.108-140
Therapeutic Implications and Future Directions
The role of programmed cell death protein 1 (PD-1) signaling in HIV-associated cardiovascular
disease (CVD) opens avenues for novel therapeutic strategies and research directions. Targeting
the PD-1 pathway holds promise for mitigating cardiovascular risk and improving outcomes in
individuals living with HIV/AIDS. Several therapeutic implications and future directions emerge
from our understanding of PD-1 signaling in HIV-associated CVD. Immune checkpoint inhibitors
targeting PD-1, such as pembrolizumab and nivolumab, have shown efficacy in attenuating
vascular inflammation, improving endothelial function, and reducing atherosclerotic burden in
preclinical models and clinical studies of other inflammatory diseases. Future research should
explore the safety and efficacy of PD-1 blockade in HIV-infected individuals with cardiovascular
complications, including randomized controlled trials to evaluate its impact on cardiovascular
outcomes. Biomarkers predictive of treatment response to PD-1 inhibitors are needed to guide
patient selection and optimize therapeutic outcomes. Future studies should focus on identifying
reliable biomarkers, such as PD-1 expression levels, immune cell subsets, or circulating
inflammatory markers, that can predict cardiovascular risk and response to PD-1-based
immunotherapy in HIV-infected individuals.141-150
Combination regimens incorporating PD-1 blockade with standard cardiovascular medications or

other immunotherapeutic agents may enhance treatment efficacy and overcome resistance
mechanisms. Synergistic effects may be achieved by targeting multiple pathways involved in
cardiovascular pathology, such as inflammation, lipid metabolism, and endothelial function.
Clinical trials investigating combination therapies are warranted to evaluate their potential benefits
in HIV-associated CVD. Further mechanistic studies are needed to elucidate the specific role of
PD-1 signaling in HIV-associated CVD. Understanding the cellular and molecular mechanisms
underlying PD-1-mediated vascular pathology, including its effects on endothelial cells, immune
cells, and vascular smooth muscle cells, will inform the development of targeted therapies and
biomarkers for cardiovascular risk stratification. Longitudinal studies with long-term follow-up
are essential to assess the safety and durability of PD-1-based immunotherapy in HIV-infected
individuals with cardiovascular complications. Monitoring for immune-related adverse events and
cardiovascular events, including myocardial infarction, stroke, and heart failure, is crucial to
ensure the optimal management of patients receiving PD-1 blockade.151-170
Conclusion
The programmed cell death protein 1 (PD-1) signaling pathway has emerged as a key player in the
pathogenesis of HIV-associated cardiovascular disease (CVD), offering promising therapeutic
implications and avenues for future research. Chronic inflammation, immune dysregulation, and
endothelial dysfunction contribute to the development and progression of cardiovascular
complications in individuals living with HIV/AIDS. PD-1 signaling influences vascular
4
inflammation, endothelial function, atherosclerosis, and myocardial injury, highlighting its

multifaceted role in cardiovascular pathology.
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50. Obeagu EI, Scott GY, Amekpor F, Obeagu GU. Implications of CD4/CD8 ratios in Human
Immunodeficiency Virus infections. Int. J. Curr. Res. Med. Sci. 2023;9(2):6-13.DOI:
10.22192/ijcrms.2023.09.02.002 links/645a4a462edb8e5f094ad37c/Implications-of-CD4-
CD8-ratios-in-Human-Immunodeficiency-Virus-infections.pdf.
51. Obeagu EI, Ochei KC, Okeke EI, Anode AC. Assessment of the level of haemoglobin and
erythropoietin in persons living with HIV in Umuahia. Int. J. Curr. Res. Med. Sci.
2016;2(4):29-33. links/5711c47508aeebe07c02496b/Assessment-of-the-level-of-
haemoglobin-and-erythropoietin-in-persons-living-with-HIV-in-Umuahia.pdf.
52. Ifeanyi OE, Obeagu GU. The Values of CD4 Count, among HIV Positive Patients in FMC
Owerri. Int. J. Curr. Microbiol. App. Sci. 2015;4(4):906-910.
https://www.academia.edu/download/38320134/Obeagu_Emmanuel_Ifeanyi_and_Obeag
u__Getrude_Uzoma.EMMA2.pdf.
9
53. Obeagu EI, Okeke EI, Anonde Andrew C. Evaluation of haemoglobin and iron profile
study among persons living with HIV in Umuahia, Abia state, Nigeria. Int. J. Curr. Res.
Biol. Med. 2016;1(2):1-5.
54. Ibebuike JE, Nwokike GI, Nwosu DC, Obeagu EI. A Retrospective Study on Human
Immune Deficiency Virus among Pregnant Women Attending Antenatal Clinic in Imo
State University Teaching Hospital. International Journal of Medical Science and Dental
Research, 2018; 1 (2):08-14.
https://www.ijmsdr.org/published%20paper/li1i2/A%20Retrospective%20Study%20on%
20Human%20Immune%20Deficiency%20Virus%20among%20Pregnant%20Women%2
0Attending%20Antenatal%20Clinic%20in%20Imo%20State%20University%20Teaching
%20Hospital.pdf.
55. Obeagu EI, Obarezi TN, Omeh YN, Okoro NK, Eze OB. Assessment of some
haematological and biochemical parametrs in HIV patients before receiving treatment in
Aba, Abia State, Nigeria. Res J Pharma Biol Chem Sci. 2014; 5:825-830.
56. Obeagu EI, Obarezi TN, Ogbuabor BN, Anaebo QB, Eze GC. Pattern of total white blood
cell and differential count values in HIV positive patients receiving treatment in Federal
Teaching Hospital Abakaliki, Ebonyi State, Nigeria. International Journal of Life Science,
Biotechnology and Pharama Research. 2014; 391:186-189.
57. Obeagu EI. A Review of Challenges and Coping Strategies Faced by HIV/AIDS
Discordant Couples. Madonna University journal of Medicine and Health Sciences. 2023;
3 (1): 7-12.
58. Oloro OH, Obeagu EI. A Systematic Review on Some Coagulation Profile in HIV
Infection. International Journal of Innovative and Applied Research. 2022;10(5):1-11.
59. Nwosu DC, Obeagu EI, Nkwuocha BC, Nwanna CA, Nwanjo HU, Amadike JN, Ezemma
MC, Okpomeshine EA, Ozims SJ, Agu GC. Alterations in superoxide dismutiase, vitamins
C and E in HIV infected children in Umuahia, Abia state. International Journal of
Advanced Research in Biological Sciences. 2015;2(11):268-271.
60. Ifeanyi OE, Uzoma OG, Stella EI, Chinedum OK, Abum SC. Vitamin D and insulin
resistance in HIV sero positive individuals in Umudike. Int. J. Curr. Res. Med. Sci.
2018;4(2):104-108.
61. Ifeanyi OE, Leticia OI, Nwosu D, Chinedum OK. A Review on blood borne viral
infections: universal precautions. Int. J. Adv. Res. Biol. Sci. 2018;5(6):60-66.
62. Nwovu AI, Ifeanyi OE, Uzoma OG, Nwebonyi NS. Occurrence of Some Blood Borne
Viral Infection and Adherence to Universal Precautions among Laboratory Staff in Federal
Teaching Hospital Abakaliki Ebonyi State. Arch Blood Transfus Disord. 2018;1(2).
63. Chinedu K, Takim AE, Obeagu EI, Chinazor UD, Eloghosa O, Ojong OE, Odunze U. HIV
and TB co-infection among patients who used Directly Observed Treatment Short-course
centres in Yenagoa, Nigeria. IOSR J Pharm Biol Sci. 2017;12(4):70-75.
64. Offie DC, Obeagu EI, Akueshi C, Njab JE, Ekanem EE, Dike PN, Oguh DN. Facilitators
and barriers to retention in HIV care among HIV infected MSM attending Community
Health Center Yaba, Lagos Nigeria. Journal of Pharmaceutical Research International.
2021;33(52B):10-19.
10
65. Obeagu EI, Obeagu GU, Ede MO, Odo EO, Buhari HA. Translation of HIV/AIDS
knowledge into behavior change among secondary school adolescents in Uganda: A
review. Medicine (Baltimore). 2023;102(49): e36599. doi:
10.1097/MD.0000000000036599. PMID: 38065920; PMCID: PMC10713174.
66. Anyiam AF, Arinze-Anyiam OC, Irondi EA, Obeagu EI. Distribution of ABO and rhesus
blood grouping with HIV infection among blood donors in Ekiti State Nigeria. Medicine
(Baltimore). 2023;102(47): e36342. doi: 10.1097/MD.0000000000036342. PMID:
38013335; PMCID: PMC10681551.
67. Echefu SN, Udosen JE, Akwiwu EC, Akpotuzor JO, Obeagu EI. Effect of Dolutegravir
regimen against other regimens on some hematological parameters, CD4 count and viral
load of people living with HIV infection in South Eastern Nigeria. Medicine (Baltimore).
2023;102(47): e35910. doi: 10.1097/MD.0000000000035910. PMID: 38013350; PMCID:
PMC10681510.
68. Fife BT, Pauken KE. The role of the PD‐1 pathway in autoimmunity and peripheral
tolerance. Annals of the New York Academy of Sciences. 2011;1217(1):45-59.
69. Francisco LM, Sage PT, Sharpe AH. The PD‐1 pathway in tolerance and autoimmunity.
Immunological reviews. 2010;236(1):219-242.
70. Opeyemi AA, Obeagu EI. Regulations of malaria in children with human
immunodeficiency virus infection: A review. Medicine (Baltimore). 2023;102(46):
e36166. doi: 10.1097/MD.0000000000036166. PMID: 37986340; PMCID:
PMC10659731.
71. Obeagu EI, Obeagu GU, Obiezu J, Ezeonwumelu C, Ogunnaya FU, Ngwoke AO, Emeka-
Obi OR,
72. Obeagu EI, Ubosi NI, Uzoma G. Storms and Struggles: Managing HIV Amid Natural
Disasters. Int. J. Curr. Res. Chem. Pharm. Sci. 2023;10(11):14-25.
73. Obeagu EI, Obeagu GU. Human Immunodeficiency Virus and tuberculosis infection: A
review of prevalence of associated factors. Int. J. Adv. Multidiscip. Res. 2023;10(10):56-
62.
74. Obeagu EI, Obeagu GU. Unmasking the Truth: Addressing Stigma in the Fight Against
HIV. Elite Journal of Public Health. 2024;2(1):8-22.
75. Obeagu EI, Obeagu GU, Okwuanaso CB. Optimizing Immune Health in HIV Patients
through Nutrition: A Review. Elite Journal of Immunology. 2024;2(1):14-33.
76. Obeagu EI, Obeagu GU. Utilization of immunological ratios in HIV: Implications for
monitoring and therapeutic strategies. Medicine. 2024;103(9): e37354.
77. Obeagu EI, Obeagu GU. CD8 Dynamics in HIV Infection: A Synoptic Review. Elite
Journal of Immunology. 2024;2(1):1-3.
78. Obeagu EI, Obeagu GU. Implications of B Lymphocyte Dysfunction in HIV/AIDS. Elite
79. Obeagu EI, Obeagu GU. Maternal Influence on Infant Immunological Responses to HIV:
A Review. Elite Journal of Laboratory Medicine. 2024;2(1):46-58.
80. Obeagu EI, Obeagu GU. Understanding B Lymphocyte Functions in HIV Infection:
Implications for Immune Dysfunction and Therapeutic Strategies. Elite Journal of
Medicine. 2024;2(1):35-46.
11
81. Obeagu EI, Obeagu GU. Platelet-Driven Modulation of HIV: Unraveling Interactions and
Implications. Journal home page: http://www. journalijiar. com.;12(01).
82. Obeagu EI, Anyiam AF, Obeagu GU. Managing Hematological Complications in HIV:
Erythropoietin Considerations. Elite Journal of HIV. 2024;2(1):65-78.
83. Obeagu EI, Obeagu GU, Hauwa BA, Umar AI. Hematocrit Variations in HIV Patients Co-
infected with Malaria: A Comprehensive Review. Journal home page: http://www.
journalijiar. com.;12(01).
84. Obeagu EI, Obeagu GU. Synergistic Effects of Blood Transfusion and HIV in Children
Under 5 Years with Severe Malaria: A Review. Elite Journal of HIV. 2024;2(1):31-50.
85. Obeagu EI, Anyiam AF, Obeagu GU. Unveiling B Cell Mediated Immunity in HIV
Infection: Insights, Challenges, and Potential Therapeutic Avenues. Elite Journal of HIV.
2024;2(1):1-5.
86. Obeagu EI, Obeagu GU. Hematocrit Fluctuations in HIV Patients Co-infected with Malaria
Parasites: A Comprehensive Review. Int. J. Curr. Res. Med. Sci. 2024;10(1):25-36.
87. Obeagu EI, Obeagu GU. Transfusion Therapy in HIV: Risk Mitigation and Benefits for
Improved Patient Outcomes. Sciences. 2024;4(1):32-7.
88. Obeagu EI, Obeagu GU. Mental Health and Psychosocial Effects of natural disaster on
HIV Patients. Sciences. 2024;4(1):38-44.
89. Obeagu EI, Obeagu GU. Eosinophil-Associated Changes in Neonatal Thymic T
Regulatory Cell Populations in HIV-Infected Pregnancies. Elite Journal of Health Science.
2024;2(1):33-42.
90. Obeagu EI, Obeagu GU. Advances in Understanding the Impact of Blood Transfusion on
Anemia Resolution in HIV-Positive Children with Severe Malaria: A Comprehensive
Review. Elite Journal of Haematology. 2024;2(1):26-41.
91. Obeagu EI, Ayogu EE, Obeagu GU. Interactions between Blood Transfusion and
Antiretroviral Medications: Implications for Patient Care. Elite Journal of Medicine.
2024;2(2):104-15.
92. Obeagu EI, Obeagu GU. Maternal Eosinophilic Responses in HIV-Positive Pregnant
Women: Unraveling Immunological Dynamics for Improved Maternal-Fetal Health. Elite
93. Obeagu EI, Anyanwu CN, Obeagu GU. Challenges and Considerations in Managing Blood
Transfusion for Individuals with HIV. Elite Journal of HIV. 2024;2(2):1-7.
94. Obeagu EI, Ubosi NI, Obeagu GU, Akram M. Early Infant Diagnosis: Key to Breaking the
Chain of HIV Transmission. Elite Journal of Public Health. 2024;2(1):52-61.
95. Obeagu EI, Obeagu GU. Understanding Hematocrit Fluctuations in HIV-Malaria
Coinfection for Improved Management. Elite Journal of Public Health. 2024;2(1):22-34.
96. Obeagu EI, Obeagu GU. The Impact of Erythropoietin on Preeclampsia in HIV-Positive
Women: A Review. Elite Journal of Nursing and Health Science. 2024;2(1):21-31.
97. Obeagu EI, Obeagu GU. Platelet Distribution Width (PDW) as a Prognostic Marker for
Anemia Severity in HIV Patients: A Comprehensive Review. Journal home page:
http://www. journalijiar. com.;12(01).
12
98. Obeagu EI, Obeagu GU. Neonatal Outcomes in Children Born to Mothers with Severe
Malaria, HIV, and Transfusion History: A Review. Elite Journal of Nursing and Health
Science. 2024;2(3):38-58.
99. Obeagu EI, Obeagu GU. Assessing Platelet Functionality in HIV Patients Receiving
Antiretroviral Therapy: Implications for Risk Assessment. Elite Journal of HIV.
2024;2(3):14-26.
100. Obeagu EI, Obeagu GU. Advancements in HIV Prevention: Africa's Trailblazing
Initiatives and Breakthroughs. Elite Journal of Public Health. 2024;2(1):52-63.
101. Obeagu EI, Obeagu GU. Maternal Influence on Infant Immunological Responses
to HIV: A Review. Elite Journal of Laboratory Medicine. 2024;2(1):46-58.
102. Obeagu EI, Obeagu GU. Counting Cells, Shaping Fates: CD4/CD8 Ratios in HIV.
Elite Journal of Scientific Research and Review. 2024;2(1):37-50.
103. Obeagu EI, Anyiam AF, Obeagu GU. Managing Hematological Complications in
HIV: Erythropoietin Considerations. Elite Journal of HIV. 2024;2(1):65-78.
104. Obeagu EI, Obeagu GU. Immune Modulation in HIV-Positive Neonates: Insights
and Implications for Clinical Management. Elite Journal of Nursing and Health Science.
2024;2(3):59-72.
105. Obeagu EI, Ayogu EE, Obeagu GU. Impact on Viral Load Dynamics:
Understanding the Interplay between Blood Transfusion and Antiretroviral Therapy in HIV
Management. Elite Journal of Nursing and Health Science. 2024;2(2):5-15.
106. Obeagu EI, Obeagu GU. Understanding B Lymphocyte Functions in HIV Infection:
Implications for Immune Dysfunction and Therapeutic Strategies. Elite Journal of
Medicine. 2024;2(1):35-46.
107. Obeagu EI, Anyanwu CN, Obeagu GU. Challenges and Considerations in
Managing Blood Transfusion for Individuals with HIV. Elite Journal of HIV. 2024;2(2):1-
7.
108. Obeagu EI, Obeagu GU. Understanding ART and Platelet Functionality:
Implications for HIV Patients. Elite Journal of HIV. 2024;2(2):60-73.
109. Obeagu EI, Obeagu GU. The Role of Blood Transfusion Strategies in HIV
Management: Current Insights and Future Directions. Elite Journal of Medicine.
2024;2(1):10-22.
110. Obeagu EI, AmaezeAA O, Obeagu GU. B Cell Deficiency and Implications in HIV
Pathogenesis: Unraveling the Complex Interplay. Elite Journal of Nursing and Health
Science. 2024;2(2):33-46.
111. Obeagu EI, Obeagu GU. Eosinophil Dynamics in Pregnancy among Women Living
with HIV: A Comprehensive Review. Int. J. Curr. Res. Med. Sci. 2024;10(1):11-24.
112. Obeagu EI, Obeagu GU. Hematocrit Fluctuations in HIV Patients Co-infected with
Malaria Parasites: A Comprehensive Review. Int. J. Curr. Res. Med. Sci. 2024;10(1):25-
36.
113. Obeagu EI, Obeagu GU. Unveiling the Role of Innate Immune Activation in
Pediatric HIV: A Review. Elite Journal of Immunology. 2024;2(3):33-44.
114. Obeagu EI, Obeagu GU. Harnessing B Cell Responses for Personalized
Approaches in HIV Management. Elite Journal of Immunology. 2024;2(2):15-28.
13
115. Obeagu EI, Obeagu GU, Hauwa BA, Umar AI. Neutrophil Dynamics: Unveiling
Their Role in HIV Progression within Malaria Patients. Journal home page: http://www.
journalijiar. com.;12(01).
116. Obeagu EI, Obeagu GU, Hauwa BA, Umar AI. Hematocrit Variations in HIV
Patients Co-infected with Malaria: A Comprehensive Review. Journal home page:
http://www. journalijiar. com.;12(01).
117. Obeagu EI, Igwe MC, Obeagu GU. The Power of Unity: Collective Efforts in
Confronting HIV Stigma. Elite Journal of Public Health. 2024;2(3):22-36.
118. Obeagu EI, Anyiam AF, Obeagu GU. Managing Anemia in HIV through Blood
Transfusions: Clinical Considerations and Innovations. Elite Journal of HIV. 2024;2(1):16-
30.
119. Obeagu EI, Obeagu GU. Maternal Eosinophilic Responses in HIV-Positive
Pregnant Women: Unraveling Immunological Dynamics for Improved Maternal-Fetal
Health. Elite Journal of Immunology. 2024;2(1):47-64.
120. Obeagu EI, Obeagu GU. Platelet Aberrations in HIV Patients: Assessing Impacts
of ART. Elite Journal of Haematology, 2024; 2 (3).:10-24.
121. Obeagu EI, Obeagu GU. Hematological Changes Following Blood Transfusion in
Young Children with Severe Malaria and HIV: A Critical Review. Elite Journal of
Laboratory Medicine. 2024;2(1):33-45.
122. Obeagu EI, Anyiam AF, Obeagu GU. Erythropoietin Therapy in HIV-Infected
Individuals: A Critical Review. Elite Journal of HIV. 2024;2(1):51-64.
123. Obeagu EI, Ubosi NI, Obeagu GU, Obeagu AA. Nutritional Strategies for
Enhancing Immune Resilience in HIV: A Review. Int. J. Curr. Res. Chem. Pharm. Sci.
2024;11(2):41-51.
124. Obeagu EI, Obeagu GU. The Crucial Role of Erythropoietin in Managing Anemia
in HIV: A Review. Elite Journal of Scientific Research and Review. 2024;2(1):24-36.
125. Obeagu EI, Obeagu GU. Impact of Maternal Eosinophils on Neonatal Immunity in
HIV-Exposed Infants: A Review. Elite Journal of Immunology. 2024;2(3):1-8.
126. Obeagu EI, Anyiam AF, Obeagu GU. Unveiling B Cell Mediated Immunity in HIV
Infection: Insights, Challenges, and Potential Therapeutic Avenues. Elite Journal of HIV.
2024;2(1):1-5.
127. Obeagu EI, Obeagu GU. Anemia and Erythropoietin: Key Players in HIV Disease
Progression. Elite Journal of Haematology, 2024; 2 (3).:42-57.
128. Obeagu EI, Obeagu GU. Platelet Dysfunction in HIV Patients: Assessing ART
Risks. Elite Journal of Scientific Research and Review. 2024;2(1):1-6.
129. Obeagu EI, Ubosi NI, Obeagu GU, Akram M. Early Infant Diagnosis: Key to
Breaking the Chain of HIV Transmission. Elite Journal of Public Health. 2024;2(1):52-61.
130. Obeagu EI, Obeagu GU. Transfusion Therapy in HIV: Risk Mitigation and Benefits
for Improved Patient Outcomes. Sciences. 2024;4(1):32-7.
131. Obeagu EI, Obeagu GU. P-Selectin and Immune Activation in HIV: Clinical
Implications. Elite Journal of Health Science. 2024;2(2):16-29.
132. Obeagu EI, Obeagu GU. Mental Health and Psychosocial Effects of natural disaster
on HIV Patients. Sciences. 2024;4(1):38-44.
14
133. Obeagu EI, Obeagu GU. Optimizing Blood Transfusion Protocols for Breast
Cancer Patients Living with HIV: A Comprehensive Review. Elite Journal of Nursing and
Health Science. 2024;2(2):1-7.
134. Obeagu EI, Obeagu GU. Advances in Understanding the Impact of Blood
Transfusion on Anemia Resolution in HIV-Positive Children with Severe Malaria: A
Comprehensive Review. Elite Journal of Haematology. 2024;2(1):26-41.
135. Obeagu EI, Obeagu GU. Transfusion-Related Complications in Children Under 5
with Coexisting HIV and Severe Malaria: A Review. Int. J. Curr. Res. Chem. Pharm. Sci.
2024;11(2):9-19.
136. Obeagu EI, Obeagu GU. Impact of Blood Transfusion on Viral Load Dynamics in
HIV-Positive Neonates with Severe Malaria: A Review. Elite Journal of Scientific
Research and Review. 2024;2(1):42-60.
137. Obeagu EI, Ayogu EE, Obeagu GU. Interactions between Blood Transfusion and
Antiretroviral Medications: Implications for Patient Care. Elite Journal of Medicine.
2024;2(2):104-5.
138. Obeagu EI, Obeagu GU. P-Selectin Expression in HIV-Associated Coagulopathy:
Implications for Treatment. Elite Journal of Haematology, 2024; 2 (3).:25-41.
139. Obeagu EI, Obeagu GU. Eosinophil-Associated Changes in Neonatal Thymic T
Regulatory Cell Populations in HIV-Infected Pregnancies. Elite Journal of Health Science.
2024;2(1):33-42.
140. Obeagu EI, Obeagu GU. Exploring the Role of L-selectin in HIV-related Immune
Exhaustion: Insights and Therapeutic Implications. Elite Journal of HIV. 2024;2(2):43-59.
141. Obeagu EI. Erythropoietin and the Immune System: Relevance in HIV
Management. Elite Journal of Health Science. 2024;2(3):23-35.
142. Obeagu EI, Obeagu GU. The Impact of Erythropoietin on Preeclampsia in HIV-
Positive Women: A Review. Elite Journal of Nursing and Health Science. 2024;2(1):21-
31.
143. Obeagu EI, Obeagu GU. Unraveling the Role of Eosinophil Extracellular Traps
(EETs) in HIV-Infected Pregnant Women: A Review. Elite Journal of Nursing and Health
Science. 2024;2(3):84-99.
144. Obeagu EI, Obeagu GU. Hematologic Considerations in Breast Cancer Patients
with HIV: Insights into Blood Transfusion Strategies. Elite Journal of Health Science.
2024;2(2):20-35.
145. Obeagu EI, Obeagu GU. L-selectin and HIV-Induced Immune Cell Trafficking:
Implications for Pathogenesis and Therapeutic Strategies. Elite Journal of Laboratory
Medicine. 2024;2(2):30-46.
146. Obeagu EI, Obeagu GU. The Intricate Relationship Between Erythropoietin and
HIV-Induced Anemia: Unraveling Pathways for Therapeutic Insights. Int. J. Curr. Res.
Chem. Pharm. Sci. 2024;11(2):30-40.
147. Obeagu EI, Obeagu GU. The Role of L-selectin in Tuberculosis and HIV
Coinfection: Implications for Disease Diagnosis and Management. Elite Journal of Public
Health. 2024;2(1):35-51.
15
148. Kalu OA, Ukibe NR, Onyenekwe CC, Okoyeagu RC, Nnaemeka WS, Onyenekwe
AJ, Ukibe EG, Ukibe BC, Ukibe VE, Obeagu EI. Assessment of Serum Cystatin C,
Microalbumin Levels and Egfr in HIV Seropositive Individuals based on Age and Gender
in NAUTH, Nnewi, Nigeria. Elite Journal of Medicine. 2024;2(3):48-59.
149. Obeagu EI, Obeagu GU. Understanding Immune Cell Trafficking in Tuberculosis-
HIV Coinfection: The Role of L-selectin Pathways. Elite Journal of Immunology.
2024;2(2):43-59.
150. Obeagu EI, Obeagu GU. Eosinophilic Changes in Placental Tissues of HIV-
Positive Pregnant Women: A Review. Elite Journal of Laboratory Medicine. 2024;2(1):14-
32.
151. Obeagu EI, Obeagu GU. P-Selectin and Platelet Activation in HIV: Implications
for Antiviral Therapy. Elite Journal of Scientific Research and Review. 2024;2(1):17-41.
152. Obeagu EI, Obeagu GU. Strength in Unity: Building Support Networks for HIV
Patients in Uganda. Elite Journal of Medicine. 2024;2(1):1-6.
153. Obeagu EI, GU EE. Understanding the Intersection of Highly Active Antiretroviral
Therapy and Platelets in HIV Patients: A Review. Elite Journal of Haematology, 2024; 2
(3).:111-7.
154. Mehraj V, Jenabian MA, Vyboh K, Routy JP. Immune suppression by myeloid cells
in HIV infection: new targets for immunotherapy. The open AIDS journal. 2014; 8:66.
155. James NE, Woodman M, DiSilvestro PA, Ribeiro JR. The perfect combination:
enhancing patient response to PD-1-based therapies in epithelial ovarian cancer. Cancers.
2020;12(8):2150.
156. Seddiki N, Picard F, Dupaty L, Lévy Y, Godot V. The potential of immune
modulation in therapeutic HIV-1 vaccination. Vaccines. 2020;8(3):419.
157. Hasan S, Awasthi P, Malik S, Dwivedi M. Immunotherapeutic strategies to induce
inflection in the immune response: therapy for cancer and COVID-19. Biotechnology and
Genetic Engineering Reviews. 2022:1-40.
158. Obeagu EI, Obeagu GU. Anemia in HIV: The Role of Erythropoietin in Disease
Progression. Elite Journal of Haematology, 2024; 2(4): 51-67
159. Obeagu EI, Obeagu GU. ART and Platelet Dynamics: Assessing Implications for
HIV Patient Care. Elite Journal of Haematology, 2024; 2(4): 68-85
160. Obeagu EI, Obeagu GU. Impact of Breastfeeding on Infant Immune Responses in
the Context of HIV. Elite Journal of Nursing and Health Science, 2024; 2(4):23-39
161. Obeagu EI, Obeagu GU. HIV-Induced Immune Exhaustion in Neonates: A Review
of Mechanisms and Implications. Elite Journal of Immunology, 2024; 2(3): 45-61
162. Obeagu EI, Obeagu GU. Immunodeficiency and Immune Reconstitution in
Pediatric HIV: Mechanisms, Challenges, and Therapeutic Strategies. Elite Journal of
Immunology, 2024; 2(3): 62-79
163. Obeagu EI, Obeagu GU. Hematological Consequences of Erythropoietin in HIV:
Clinical Implications. Elite Journal of Haematology, 2024; 2(4): 86-104
16
164. Obeagu EI, Obeagu GU. GATA-1 and Hematopoietic Stem Cell Dysfunction in
HIV-Related Hematological Malignancies: A Review. Elite Journal of Haematology,
2024; 2(4): 105-122
165. Obeagu EI, Obeagu GU. Exploration of Intricate Relationship between GATA-1
and Anemia in HIV. Elite Journal of Haematology, 2024; 2(4): 123-140
166. Obeagu EI, Obeagu GU. GATA-1 and Immune Dysregulation in HIV/AIDS:
Implications for Therapy. Elite Journal of HIV, 2024; 2(3): 69-85
167. Obeagu EI, Obeagu GU. The Role of GATA-1 in Erythropoietin Response and
Resistance in HIV/AIDS. Elite Journal of HIV, 2024; 2(4): 1-17
168. Obeagu EI, Obeagu GU. Understanding the Role of GATA-1 in T-Cell
Development in the Context of HIV Infection. Elite Journal of HIV, 2024; 2(4): 18-34
169. Obeagu EI, Obeagu GU. Programmed Cell Death Protein 1 (PD-1) Pathway
Modulation in HIV/AIDS: From Bench to Bedside. Elite Journal of HIV, 2024; 2(4): 35-
53
170. Obeagu EI, Obeagu GU. Programmed Cell Death Protein 1 (PD-1) and Immune
Checkpoint Inhibitors in HIV-Related Lymphomas: Current Insights and Future
Directions. Elite Journal of Immunology, 2024; 2(4): 1-17
17
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Programmed Cell Death Protein 1 (PD-1) Signaling in HIV-Associated

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Emmanuel Ifeanyi Obeagu Getrude Uzoma Obeagu

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Programmed Cell Death Protein 1 (PD-1) Signaling in HIV-Associated Cardiovascular

Cardiovascular disease (CVD) remains a significant cause of morbidity and mortality in

factors, such as hypertension, dyslipidemia, and smoking, as well as HIV-specific factors,

PD-1 Signaling in Vascular Inflammation and Endothelial Dysfunction

Endothelial dysfunction is characterized by impaired endothelium-dependent vasodilation,

Role of PD-1 Signaling in Atherosclerosis and Myocardial Injury

Therapeutic Implications and Future Directions

Combination regimens incorporating PD-1 blockade with standard cardiovascular medications or

inflammation, endothelial function, atherosclerosis, and myocardial injury, highlighting its

Nigeria. J Pub Health Nutri. 2022; 5 (8). 2022;137.

Tertiary Health Institution in Enugu State. Asian Journal of Research in Infectious

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