Available online on 15.06.2025 at ijmspr.com
International Journal of Medical Sciences and Pharma Research
Open Access to Medical Science and Pharma Research
Copyright © 2025 The Author(s): This is an open-access article distributed under the terms of the CC BY-NC 4.0 which permits unrestricted use, distribution, and reproduction in any medium for non-commercial use provided the original author and source are credited
Endothelial Dysfunction in HIV-Infected Sickle Cell Disease Patients: A Review
Emmanuel Ifeanyi Obeagu 1* and Olga Geogievna Goryacheva 2
1 Department of Biomedical and Laboratory Science, Africa University, Zimbabwe
2 Perm State Medical University named after Academician E.A. Wagner, Russia
|
Article Info: _______________________________________________ Article History: Received 07 Jan 2025 Reviewed 16 Feb 2025 Accepted 03 March 2025 Published 15 June 2025 _______________________________________________ Cite this article as: Obeagu EI, Goryacheva OG, Endothelial Dysfunction in HIV-Infected Sickle Cell Disease Patients: A Review, International Journal of Medical Sciences & Pharma Research, 2025; 11(2):27-31 DOI: http://dx.doi.org/10.22270/ijmspr.v11i2.145 _______________________________________________ *Address for Correspondence: Emmanuel Ifeanyi Obeagu, Department of Biomedical and Laboratory Science, Africa University, Zimbabwe |
Abstract _______________________________________________________________________________________________________________ Endothelial dysfunction is a significant complication in patients with both sickle cell disease (SCD) and human immunodeficiency virus (HIV) infection, contributing to increased morbidity and mortality. In SCD, chronic hemolysis leads to elevated levels of free hemoglobin and reactive oxygen species, resulting in decreased nitric oxide (NO) availability and impaired endothelial function. Concurrently, HIV infection is characterized by persistent immune activation and inflammation, further exacerbating endothelial injury. The interplay between these two conditions creates a synergistic effect that heightens the risk of thrombotic events, cardiovascular disease, and organ damage. This review aims to elucidate the molecular mechanisms underlying endothelial dysfunction in SCD-HIV co-infected patients, focusing on the roles of oxidative stress, inflammatory cytokines, and the upregulation of endothelial adhesion molecules. We also examine the contributions of dysregulated coagulation pathways to the vascular complications observed in this population. Understanding these mechanisms is crucial for developing effective therapeutic strategies to mitigate endothelial dysfunction and improve patient outcomes. Keywords: Endothelial dysfunction, Sickle cell disease, HIV infection, Vascular inflammation, Nitric oxide |
Introduction
Endothelial dysfunction is a critical factor contributing to the vascular complications observed in various diseases, including sickle cell disease (SCD) and human immunodeficiency virus (HIV) infection. The endothelium, a monolayer of cells lining blood vessels, plays a vital role in maintaining vascular homeostasis through the regulation of blood flow, vascular tone, and the prevention of thrombosis. In patients with SCD, the chronic hemolysis of red blood cells and the resulting oxidative stress lead to significant alterations in endothelial function. Simultaneously, HIV infection induces a state of systemic inflammation and immune activation that further compromises endothelial integrity. The coexistence of these two conditions creates a unique pathological environment that increases the risk of severe vascular complications.1-3 SCD is a genetic disorder characterized by the production of abnormal hemoglobin (HbS), which causes red blood cells to assume a sickle shape under low oxygen conditions. These sickle-shaped cells are rigid and prone to causing vaso-occlusive crises, leading to ischemia and organ damage. The chronic hemolysis associated with SCD releases free hemoglobin into the circulation, which can scavenge nitric oxide (NO), a crucial vasodilator. This depletion of NO contributes to endothelial dysfunction and vascular inflammation, which are hallmarks of SCD.4-5 HIV infection also has profound effects on endothelial function. The virus itself can directly infect endothelial cells, leading to cellular dysfunction. Moreover, HIV infection induces persistent immune activation characterized by elevated levels of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). These cytokines promote endothelial activation, increase permeability, and contribute to a pro-thrombotic state. As a result, HIV-infected individuals face an increased risk of cardiovascular disease and thrombotic events, further complicating the management of their overall health.6-7
The combination of SCD and HIV infection exacerbates endothelial dysfunction, leading to an increased incidence of thrombotic complications, including stroke and acute chest syndrome. Studies have demonstrated that individuals with both SCD and HIV have a higher prevalence of endothelial injury markers and a greater degree of vascular inflammation compared to those with either condition alone. This synergistic effect underscores the importance of understanding the molecular mechanisms involved in endothelial dysfunction in this patient population.8-9 The interplay between oxidative stress, inflammation, and endothelial activation is central to the pathophysiology of endothelial dysfunction in SCD-HIV co-infected individuals. In SCD, the hemolytic process generates excessive reactive oxygen species (ROS) that damage endothelial cells and impair their function. Additionally, the inflammatory milieu created by HIV infection further exacerbates oxidative stress and endothelial injury. Together, these factors create a vicious cycle that perpetuates vascular dysfunction and increases the risk of complications.10-11 Given the significant implications of endothelial dysfunction in SCD-HIV co-infection, it is crucial to explore potential therapeutic strategies that target this aspect of disease management. Hydroxyurea, a cornerstone treatment for SCD, has been shown to improve endothelial function by increasing fetal hemoglobin levels, reducing hemolysis, and decreasing inflammation. Antiretroviral therapy (ART) for HIV infection also plays a critical role in reducing systemic inflammation and improving overall vascular health. Emerging therapies, such as L-arginine supplementation and antioxidant treatments, offer promising avenues for improving endothelial function and mitigating vascular complications in this patient population.12-13 This review aims to provide an in-depth analysis of the pathophysiological mechanisms driving endothelial dysfunction in SCD-HIV co-infected individuals. By understanding these interactions, clinicians and researchers can develop targeted strategies to mitigate vascular complications and improve patient outcomes.
Molecular Mechanisms of Endothelial Dysfunction in SCD-HIV Co-Infection
Endothelial dysfunction in patients co-infected with sickle cell disease (SCD) and human immunodeficiency virus (HIV) arises from a complex interplay of molecular mechanisms that disrupt normal vascular homeostasis.14
In SCD, the hemolysis of red blood cells leads to the release of free hemoglobin (Hb) into the bloodstream. Free Hb can scavenge nitric oxide (NO), a crucial vasodilator produced by endothelial cells that regulates vascular tone and promotes blood flow. The depletion of NO results in impaired vasodilation and contributes to increased vascular resistance. Additionally, the release of hemoglobin promotes the formation of reactive oxygen species (ROS), further exacerbating oxidative stress. ROS can damage endothelial cells by causing lipid peroxidation, protein oxidation, and DNA damage, leading to cellular dysfunction and apoptosis.15-17
HIV infection induces a state of chronic immune activation characterized by elevated levels of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and C-reactive protein (CRP). These cytokines play a pivotal role in the pathogenesis of endothelial dysfunction. TNF-α, for instance, can promote endothelial cell activation, leading to increased expression of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). This upregulation enhances the recruitment of inflammatory cells to the endothelium, perpetuating the inflammatory cycle and contributing to vascular damage.18-20
Endothelial progenitor cells (EPCs) are crucial for maintaining endothelial health and repairing injured blood vessels. In patients with SCD and HIV, the availability and functionality of EPCs may be compromised. Studies have shown that both SCD and HIV infection can lead to reduced circulating levels of EPCs and impaired endothelial regeneration. The combination of oxidative stress and chronic inflammation can hinder EPC mobilization and function, resulting in diminished repair capacity and exacerbation of endothelial dysfunction.21-22
Endothelial dysfunction is closely linked to alterations in coagulation pathways. In SCD-HIV co-infected patients, the inflammatory environment promotes the activation of the coagulation cascade, leading to a pro-thrombotic state. Increased levels of tissue factor (TF) and von Willebrand factor (vWF) can result in heightened platelet activation and aggregation, further increasing the risk of thrombotic events. The interplay between inflammation and coagulation creates a feedback loop that amplifies endothelial injury and compromises vascular integrity.23-25
Emerging evidence suggests that the gut microbiome may play a role in modulating endothelial function in SCD-HIV co-infected individuals. Dysbiosis, or an imbalance in the gut microbiota, can contribute to systemic inflammation and endothelial dysfunction. The production of metabolites such as short-chain fatty acids (SCFAs) by beneficial gut bacteria has been shown to exert protective effects on endothelial cells. Conversely, the presence of pathogenic bacteria may exacerbate inflammation and oxidative stress, further compromising endothelial health.26-28
Genetic predispositions and epigenetic modifications also contribute to endothelial dysfunction in SCD-HIV co-infection. Genetic variations in genes related to inflammation, oxidative stress response, and coagulation may influence individual susceptibility to vascular complications. Additionally, epigenetic changes, such as DNA methylation and histone modifications, can alter gene expression patterns involved in endothelial function.29-30
Potential Therapeutic Approaches
Addressing endothelial dysfunction in patients co-infected with sickle cell disease (SCD) and human immunodeficiency virus (HIV) is crucial for improving their overall health and reducing the risk of cardiovascular complications. A multifaceted approach that combines pharmacological interventions, lifestyle modifications, and supportive therapies may help restore endothelial function and mitigate the adverse effects of both conditions.31-32
Hydroxyurea is a cornerstone treatment for SCD that has shown promise in improving endothelial function. It acts by increasing fetal hemoglobin levels, reducing hemolysis, and lowering inflammation. By decreasing the release of free hemoglobin into the circulation, hydroxyurea helps preserve nitric oxide availability, thus promoting vasodilation and improving blood flow. Additionally, hydroxyurea has been associated with reduced levels of inflammatory markers, contributing to a more favorable vascular environment. Given its dual benefits in managing SCD and its potential to improve endothelial function, hydroxyurea should be considered a key component of the therapeutic regimen for SCD-HIV co-infected patients.33-36
Effective ART is essential for managing HIV infection and reducing associated immune activation and inflammation. By controlling viral replication and restoring immune function, ART can significantly decrease the levels of pro-inflammatory cytokines that contribute to endothelial dysfunction. Studies have demonstrated that certain ART regimens can improve endothelial health by reducing inflammation and oxidative stress. Incorporating ART into the treatment plan for patients with SCD and HIV can help mitigate the vascular complications associated with both conditions.37-39
Antioxidants play a crucial role in neutralizing reactive oxygen species (ROS) and mitigating oxidative stress. Supplementation with antioxidants, such as vitamins C and E, N-acetylcysteine, and coenzyme Q10, may help improve endothelial function in SCD-HIV co-infected patients. These antioxidants can enhance the bioavailability of nitric oxide and protect endothelial cells from oxidative damage. Clinical studies evaluating the efficacy of antioxidant supplementation in this population are warranted to determine optimal dosing and long-term benefits.40-42
Given the role of chronic inflammation in endothelial dysfunction, the use of anti-inflammatory agents may offer therapeutic benefits. Non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids can help reduce inflammation and improve vascular health. Additionally, novel anti-inflammatory therapies targeting specific cytokines, such as TNF-α inhibitors, may provide more precise interventions to alleviate endothelial dysfunction. Ongoing research is needed to assess the safety and efficacy of these agents in SCD-HIV co-infected patients.43-45
Lifestyle interventions can complement pharmacological treatments and improve overall vascular health. Encouraging patients to adopt a heart-healthy diet rich in fruits, vegetables, whole grains, and omega-3 fatty acids can help reduce inflammation and oxidative stress. Regular physical activity has also been shown to enhance endothelial function and improve cardiovascular health. Implementing smoking cessation programs is essential, as smoking exacerbates endothelial dysfunction and increases cardiovascular risk. Education on stress management techniques, such as mindfulness and relaxation exercises, can further support overall well-being.46
Emerging therapeutic strategies targeting specific pathways involved in endothelial dysfunction hold promise for the future. For instance, medications that enhance nitric oxide signaling, such as soluble guanylate cyclase stimulators, may help restore endothelial function in SCD-HIV co-infected patients. Other agents that target inflammation and coagulation pathways, such as direct oral anticoagulants or thrombin inhibitors, could also be beneficial in reducing thrombotic risk. Continued research into these novel agents is crucial for identifying effective treatment options for this patient population.47
A multidisciplinary care approach that involves collaboration among hematologists, infectious disease specialists, cardiologists, and nutritionists can provide comprehensive management for patients with SCD and HIV. Regular monitoring of endothelial function, cardiovascular health, and overall disease management is essential for optimizing treatment outcomes. By addressing the complex interactions between SCD and HIV, a coordinated care plan can enhance the quality of life and reduce the risk of complications in affected patients.48
Conclusion
Endothelial dysfunction in SCD-HIV co-infected individuals is driven by a complex interplay of oxidative stress, inflammation, adhesion molecule upregulation, and hypercoagulability. The synergistic effects of chronic hemolysis, HIV-induced immune activation, and dysregulated coagulation pathways create a heightened risk of vascular complications, including thrombotic events, vaso-occlusion, and organ damage. While hydroxyurea and ART remain cornerstone therapies, emerging treatments targeting NO bioavailability, oxidative stress, and endothelial activation hold promise for improving vascular health in this population. Further research is needed to develop tailored therapeutic strategies to mitigate endothelial dysfunction and improve clinical outcomes in SCD-HIV patients.
Conflict of Interest: Author declares no potential conflict of interest with respect to the contents, authorship, and/or publication of this article.
Source of Support: Nil
Funding: The authors declared that this study has received no financial support.
Informed Consent Statement: Not applicable.
Data Availability Statement: The data supporting in this paper are available in the cited references.
Ethics approval: Not applicable.
References
1. Owusu ED, Visser BJ, Nagel IM, Mens PF, Grobusch MP. The interaction between sickle cell disease and HIV infection: a systematic review. Clinical Infectious Diseases. 2015; 60(4):612-626. https://doi.org/10.1093/cid/ciu832 PMid:25344542
2. Boateng LA, Ngoma AM, Bates I, Schonewille H. Red blood cell alloimmunization in transfused patients with sickle cell disease in sub-Saharan Africa; a systematic review and meta-analysis. Transfusion Medicine Reviews. 2019; 33(3):162-169. https://doi.org/10.1016/j.tmrv.2019.06.003 PMid:31345590
3. Ola B, Olushola O, Ebenso B, Berghs M. Sickle Cell Disease and Its Psychosocial Burdens in Africa. InSickle Cell Disease in Sub-Saharan Africa 2024: 67-80. Routledge. https://doi.org/10.4324/9781003467748-7
4. Obeagu EI, Reducing Hospitalization Rates: The Preventive Benefits of Blood Transfusions in HIV Care, International Journal of Medical Sciences and Pharma Research, 2024;10(3):29-34 https://doi.org/10.22270/ijmspr.v10i3.111
5. Ochocinski D, Dalal M, Black LV, Carr S, Lew J, Sullivan K, Kissoon N. Life-threatening infectious complications in sickle cell disease: a concise narrative review. Frontiers in Pediatrics. 2020; 8:38. https://doi.org/10.3389/fped.2020.00038 PMid:32154192 PMCid:PMC7044152
6. 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
7. 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).
8. 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
9. 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. https://doi.org/10.22270/ijmspr.v10i2.95
10. Obeagu EI, Obeagu GU. Transfusion Therapy in HIV: Risk Mitigation and Benefits for Improved Patient Outcomes. Asian J Dental Health Sci, 2024; 4(1):32-7. https://doi.org/10.22270/ajdhs.v4i1.62
11. Obeagu EI, Obeagu GU. Advancements in HIV Prevention: Africa's Trailblazing Initiatives and Breakthroughs. Elite Journal of Public Health, 2024; 2 (1): 52-63
12. 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):1-17
13. Obeagu EI, Obeagu GU. Understanding ART and Platelet Functionality: Implications for HIV Patients. Elite Journal of HIV, 2024; 2(2): 60-73 1
14. 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
15. Obeagu EI, Obeagu GU. Impact of Maternal Eosinophils on Neonatal Immunity in HIVExposed Infants: A Review. Elite Journal of Immunology, 2024; 2(3): 1-18 https://doi.org/10.22270/ajdhs.v4i2.82
16. Obeagu EI, Obeagu GU, Obiezu J, Ezeonwumelu C, Ogunnaya FU, Ngwoke AO, Emeka-Obi OR, Ugwu OP. Hematologic Support in HIV Patients: Blood Transfusion Strategies and Immunological Considerations. Newport International Journal of Biological and Applied Sciences (NIJBAS) 2023. http://hdl.handle.net/20.500.12493/14626
17. Ntsekhe M, Baker JV. Cardiovascular disease among persons living with HIV: new insights into pathogenesis and clinical manifestations in a global context. Circulation. 2023; 147(1):83-100. https://doi.org/10.1161/CIRCULATIONAHA.122.057443 PMid:36576956
18. Obare LM, Temu T, Mallal SA, Wanjalla CN. Inflammation in HIV and its impact on atherosclerotic cardiovascular disease. Circulation research. 2024; 134(11):1515-1545 https://doi.org/10.1161/CIRCRESAHA.124.323891 PMid:38781301 PMCid:PMC11122788
19. Hmiel L, Zhang S, Obare LM, Santana MA, Wanjalla CN, Titanji BK, Hileman CO, Bagchi S. Inflammatory and immune mechanisms for atherosclerotic cardiovascular disease in HIV. International journal of molecular sciences. 2024; 25(13):7266. https://doi.org/10.3390/ijms25137266 PMid:39000373 PMCid:PMC11242562
20. Obeagu EI, Obeagu GU. Platelet Aberrations in HIV Patients: Assessing Impacts of ART. Elite Journal of Haematology, 2024; 2(3): 10-24
21. Obeagu EI, Obeagu GU. Harnessing B Cell Responses for Personalized Approaches in HIV Management. Elite Journal of Immunology, 2024; 2(2): 15-28
22. Belisário AR, Blatyta PF, Vivanco D, Oliveira CD, Carneiro-Proietti AB, Sabino EC, de Almeida-Neto C, Loureiro P, Máximo C, de Oliveira Garcia Mateos S, Flor-Park MV. Association of HIV infection with clinical and laboratory characteristics of sickle cell disease. BMC Infectious Diseases. 2020; 20(1):638. https://doi.org/10.1186/s12879-020-05366-z PMid:32854639 PMCid:PMC7457248
23. Obeagu EI, Addressing Sleep Disturbances: Blood Transfusions and Improved Sleep Patterns in HIV Patients, International Journal of Medical Sciences and Pharma Research, 2024;10(3):43-48 https://doi.org/10.22270/ijmspr.v10i3.113
24. Gill AF, Ahsan MH, Lackner AA, Veazey RS. Hematologic abnormalities associated with simian immunodeficieny virus (SIV) infection mimic those in HIV infection. Journal of Medical Primatology. 2012; 41(3):214-224. https://doi.org/10.1111/j.1600-0684.2012.00543.x PMid:22620272 PMCid:PMC3367385
25. Nouraie M, Nekhai S, Gordeuk VR. Sickle cell disease is associated with decreased HIV but higher HBV and HCV comorbidities in US hospital discharge records: a cross-sectional study. Sexually transmitted infections. 2012; 88(7):528-533. https://doi.org/10.1136/sextrans-2011-050459 PMid:22628662 PMCid:PMC3456988
26. 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.
27. 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
28. 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
29. 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
30. Obeagu EI, Obeagu, GU. Impact of Blood Transfusion on Viral Load Dynamics in HIVPositive Neonates with Severe Malaria: A Review. Elite Journal of Scientific Research and Review, 2024; 2(1): 42-60
31. 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
32. 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
33. Obeagu EI, Obeagu GU. P-Selectin Expression in HIV-Associated Coagulopathy: Implications for Treatment. Elite Journal of Haematology, 2024; 2(3): 25-41
34. Obeagu EI, Obeagu GU. P-Selectin and Immune Activation in HIV: Clinical Implications. Elite Journal of Health Science, 2024; 2(2): 16-29
35. Obeagu EI, Amaeze AA, Ogbu ISI, 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
36. Obeagu EI, Obeagu, GU. Platelet Dysfunction in HIV Patients: Assessing ART Risks. Elite Journal of Scientific Research and Review, 2024; 2(1): 1-16
37. Kibaru EG, Nduati R, Wamalwa D, Kariuki N. Impact of highly active antiretroviral therapy on hematological indices among HIV-1 infected children at Kenyatta National Hospital-Kenya: retrospective study. AIDS research and therapy. 2015; 12:1-8. https://doi.org/10.1186/s12981-015-0069-4 PMid:26279668 PMCid:PMC4537535
38. Enawgaw B, Alem M, Addis Z, Melku M. Determination of hematological and immunological parameters among HIV positive patients taking highly active antiretroviral treatment and treatment naïve in the antiretroviral therapy clinic of Gondar University Hospital, Gondar, Northwest Ethiopia: a comparative cross-sectional study. BMC hematology. 2014; 14:1-7. https://doi.org/10.1186/2052-1839-14-8 PMid:24666771 PMCid:PMC3994311
39. Gudina A, Wordofa M, Urgessa F. Immuno-hematological parameters among adult HIV patients before and after initiation of Dolutegravir based antiretroviral therapy, Addis Ababa, Ethiopia. Plos one. 2024; 19(10):e0310239. https://doi.org/10.1371/journal.pone.0310239 PMid:39480901 PMCid:PMC11527299
40. Geletaw T, Tadesse MZ, Demisse AG. Hematologic abnormalities and associated factors among HIV infected children pre-and post-antiretroviral treatment, North West Ethiopia. Journal of blood medicine. 2017:99-105. https://doi.org/10.2147/JBM.S137067 PMid:28831276 PMCid:PMC5552149
41. Jegede FE, Oyeyi TI, Abdulrahman SA, Mbah HA, Badru T, Agbakwuru C, Adedokun O. Effect of HIV and malaria parasites co-infection on immune-hematological profiles among patients attending anti-retroviral treatment (ART) clinic in Infectious Disease Hospital Kano, Nigeria. PLoS One. 2017; 12(3):e0174233. https://doi.org/10.1371/journal.pone.0174233 PMid:28346490 PMCid:PMC5367709
42. Obeagu EI, Obeagu GU. ART and Platelet Dynamics: Assessing Implications for HIV Patient Care. Elite Journal of Haematology. 2024; 2(4):68-85.
43. 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.
44. Ciccacci F, Lucaroni F, Latagliata R, Morciano L, Mondlane E, Balama M, Tembo D, Gondwe J, Orlando S, Palombi L, Marazzi MC. Hematologic alterations and early mortality in a cohort of HIV positive African patients. PLoS One. 2020; 15(11):e0242068. https://doi.org/10.1371/journal.pone.0242068 PMid:33170905 PMCid:PMC7654783
45. Ashenafi G, Tibebu M, Tilahun D, Tsegaye A. Immunohematological Outcome Among Adult HIV Patients Taking Highly Active Antiretroviral Therapy for at Least Six Months in Yabelo Hospital, Borana, Ethiopia. Journal of Blood Medicine. 2023:543-554. https://doi.org/10.2147/JBM.S419414 PMid:37881654 PMCid:PMC10595970
46. Obeagu EI, Goryacheva OG. The Role of Inflammation in HIV and Sickle Cell Disease Co-Morbidity. Lifeline HIV, 2025; 3(1): 1-12
47. Obeagu EI, Goryacheva OG. Oxidative Stress in HIV and Sickle Cell Disease: A Double Burden. Lifeline HIV, 2025; 3(1): 13-24
48. Obeagu EI, Goryacheva OG. HIV and Sickle Cell Disease: A Focus on Liver Dysfunction. Lifeline HIV, 2025; 3(1): 25-40