Immune Dysregulation Linking Malaria HIV Infection Immunosuppressive Therapy and Ageing: A Critical Narrative Review
Uzuazokaro Mark-Maria Agatemor *
Department of Research and Development, First Focus Research, Nottingham, United Kingdom.
Isioma Agatemor
Department of Nursing Services, Queens Medical Centre, Nottingham, United Kingdom.
*Author to whom correspondence should be addressed.
Abstract
Background: Malaria, HIV infection, therapeutic immunosuppression and ageing influence immune function through distinct mechanisms. Their clinical overlap raises questions about infection susceptibility, inflammatory injury and the safety of combined treatment. A coherent synthesis requires distinguishing immune activation from effective protection and mechanistic plausibility from demonstrated clinical benefit.
Objective: To examine evidence connecting these conditions and identify implications for treatment and research, with particular attention to malaria and HIV coinfection, transplantation and interventions targeting immune ageing.
Approach: This critical narrative review draws on the targeted web-assisted retrieval of primary biomedical publications and authoritative guidance. Historical cohort findings are considered alongside pharmacokinetic trials, longitudinal ageing studies and contemporary clinical recommendations. The review does not claim exhaustive retrieval, pooled effect estimation or formal certainty grading.
Synthesis: HIV-associated immune impairment is associated with greater malaria morbidity in historical cohorts, while malaria can transiently increase circulating HIV RNA. Antiretroviral treatment and preventive measures modify these relationships. Drug interactions can alter antimalarial and transplant immunosuppressant exposure independently of immune status. HIV-related inflammation and epigenetic ageing overlap with features of immune ageing, but biomarker changes do not establish a uniform acceleration of organismal ageing. Low-dose mTOR inhibition illustrates the dependence of immune effects on dose and context, with early signals of benefit followed by a negative phase 3 respiratory-illness endpoint.
Conclusion: The strongest actionable evidence supports sustained HIV suppression, malaria prevention, prompt diagnostic testing and careful management of drug interactions. A combined assessment of exposure, pathogen control, immune function and organ reserve offers a useful research framework, but requires prospective validation in populations where these risks coexist.
Keywords: Malaria, HIV, immunosuppression, immunosenescence, inflammation, antiretroviral therapy, transplantation, mTOR