Vol. 8 No. 07 (2026): Volume 08 Issue 07

Sickle cell anemia (SCA) is a hereditary hemoglobinopathy characterized by chronic hemolysis, vaso-occlusive episodes, endothelial dysfunction, inflammation, and progressive multiorgan injury. Among the numerous molecular abnormalities associated with the disease, nitric oxide (NO) deficiency has emerged as a central contributor to vascular dysfunction and disease progression. Nitric oxide is an essential endogenous signaling molecule that regulates vascular tone, platelet aggregation, leukocyte adhesion, oxidative balance, and endothelial homeostasis. In SCA, continuous intravascular hemolysis releases cell-free hemoglobin and arginase into the circulation, leading to rapid nitric oxide scavenging and depletion of its precursor, L-arginine. Simultaneously, oxidative stress, chronic inflammation, and endothelial injury further impair nitric oxide synthesis and bioavailability. The resulting imbalance contributes to vasoconstriction, pulmonary hypertension, endothelial activation, recurrent vaso-occlusion, and chronic organ damage.

This review critically synthesizes available evidence from the provided literature to examine the molecular mechanisms responsible for nitric oxide deficiency, its contribution to disease pathophysiology, and current therapeutic interventions aimed at restoring nitric oxide signaling. The review integrates evidence regarding oxidative stress regulation, erythropoiesis, nutritional metabolism, antioxidant therapy, and comprehensive disease management to establish a multidimensional understanding of nitric oxide biology in sickle cell anemia. Particular emphasis is placed on endothelial dysfunction, redox imbalance, immune regulation, and metabolic alterations that collectively influence nitric oxide homeostasis. Therapeutic approaches including hydroxyurea-associated nitric oxide generation, antioxidant supplementation, nutritional optimization, erythropoietin therapy, immunization-based preventive care, and emerging molecular strategies are critically discussed. The review further identifies important knowledge gaps and proposes future directions for precision medicine targeting nitric oxide pathways in sickle cell disease.

Background: Nigeria remains affected by HIV and highly dependent on donor-funded programmes. Reductions in international HIV financing may threaten HIV testing, treatment, viral suppression, and epidemic control. This study assessed the epidemiological impact of funding withdrawal on HIV transmission, care-continuum performance, and AIDS-related mortality in Nigeria.

Methods: A deterministic compartmental dynamic HIV transmission model was developed and calibrated using Nigeria-specific epidemiological and HIV care-continuum indicators obtained from UNAIDS, WHO, NACA, PEPFAR, and CDC reports. The model incorporated HIV transmission, diagnosis, antiretroviral therapy (ART) initiation, viral suppression, treatment interruption, and AIDS-related mortality. Five funding-retention scenarios were simulated over a 10-year projection horizon (2026–2036): status quo (100% retained funding), mild withdrawal (80%), moderate withdrawal (60%), severe withdrawal (40%), and extreme withdrawal (20%). Probabilistic sensitivity analyses using 500 Monte Carlo simulations were performed to evaluate model uncertainty.

Results: Under the extreme withdrawal scenario, diagnosis coverage declined to approximately 70%, ART coverage fell below 50%, and viral suppression decreased to nearly one-third of people living with HIV by 2036. Severe and extreme withdrawal scenarios produced marked increases in HIV incidence and AIDS-related mortality, with more than 700,000 excess HIV infections and approximately 90,000 excess AIDS-related deaths projected over the study period. The epidemiological burden increased disproportionately when retained funding fell below 60%. Abrupt funding withdrawal produced worse outcomes than gradual phased withdrawal. Sensitivity analyses identified HIV transmission rates, viral suppression, and AIDS-related mortality rates as key drivers of model outcomes.

Conclusion: Substantial reductions in external HIV financing could reverse recent gains in HIV epidemic control in Nigeria, resulting in worsening HIV care-continuum performance, increasing HIV transmission, and rising AIDS-related mortality. Sustained HIV financing and carefully managed transition strategies are essential to preserve long-term epidemic control.