The significant variations in serum iron, transferrin saturation and total iron binding capacity (TIBC) obtained in HIV-1 infected subjects were indications of derangement in iron metabolism. In addition, serum iron was found to have negative correlation with CD4+
T- lymphocytes [Table
. These findings corroborated the results of some other workers who had previously observed that iron impaired the CD4+
T cell sub population in vitro
]. High plasma iron and body iron stores have the potential of promoting free radical generation and oxidative stress via the popular Fenton/Haber –Weiss reaction [2
]. The various metabolic derangements predispose HIV patients to metabolic acidosis [30
] which promotes reduced binding of iron molecules to transferrin with resultant increase in serum free iron [7
]. It is of importance to note that poorly liganded iron with resultant increased body free iron which readily reacts with free radicals, particularly hydroxyl radicals had been observed in many pathological processes and inflammatory diseases [41
]. The possibility of occurrence of this scenario is therefore high in an event of metabolic acidosis of HIV infection.Furthermore, the fact that excessive free iron promotes oncogene activation and tumour proliferation underscores the possible involvement of derangement in iron metabolism in incidence of HIV associated cancers like Kaposi’s sarcoma and lymphomas [20
Generation of free radicals has been implicated in the depletion of the antioxidant stores and progressive loss of CD4+
T helper cells, which is indicated by the significantly lower levels of vitamin C obtained in our test subjects. In this study, the fact that CD4+
T cell counts correlated positively with the antioxidant levels [Table
, and supplementation with antioxidants such as zinc and selenium have been shown to improve the immune status in HIV-1 patients supports their usefulness as adjuvants to antiretroviral therapy [31
]. However, the low antioxidant status observed in our study can also be attributed to generalized cachexia, nutrient malabsorption and diarrhea commonly found in HIV-1 infections.
Another dimension of consequences of increased plasma iron is the fact that iron- rich environment not only renders the patients more susceptible to microbial infections like Mycobacterium tuberculosis, Candida albicans, Salmonella and hepatitis viruses B and C but promotes their proliferation with a significant contribution to the morbidity and mortality that accompanies HIV-1 infection.
The burden of elevated plasma iron can be further compounded by alcohol ingestion, iron and multivitamins supplementation. Alcohol not only contains iron, but aids the absorption of iron from the intestines [7
]. The synergistic effect of iron supplementation and alcohol consumption in HIV infection can therefore be better imagined. It is also pertinent to note that iron supplements and iron containing multivitamins are sold off the counters in pharmacies and their usage without prescription are common practices particularly in developing countries.
Other possible contributor to raised plasma iron is a condition termed African iron overload, with distinct features from the well characterized HLA linked haemochromatosis observed in Caucasians and iron overload unexplained by dietary, medicinal or excessive blood transfusion with clinical significance which had been observed in Africans and Americans of African descents[35
]. It is therefore plausible to suggest an interaction between an unidentified gene and dietary iron content in addition to derangement in intracellular iron metabolism to be possible contributors to the elevated serum iron observed in the patients studied. Our results however confounded our expectation which the burden of helminthiasis and malnutrition common in Africa could have on serum iron levels. This underscores the clinical significance of this study.
Although the retrospective nature of this study was a limitation, there was no concurrence in the association of iron status with severity of the disease in other prospective and retrospective studies. For example, no correlation was observed between plasma iron levels and markers of severity of HIV disease in some Malawian sero-positive pregnant women [21
]. Contrastly, in another cross sectional study of some sero-positive pregnant Zimbabwean women receiving iron supplementation, ferritin level was found to be an independent predictor of viral load [40
]. Although evidences of elevated iron status in HIV infection were observed in some similar retrospective studies [5
], this was however not the case in many others [21
]. Furthermore, associations between iron accumulation and such adverse conditions like anaemia commonly unresponsive to iron supplementation, observed to increase the incidence of opportunistic infection and shorter survival periods led credence to the critical role of iron metabolism in the pathogenesis of HIV disease [6
From all indications, the virus-host iron status interaction is yet to be fully understood. While some viruses selectively infect iron acquiring cells by binding to transferrin receptor-1 during cell entry, others alter the expression of proteins involved in iron homeostasis such as human haemochromatosis protein; (HFE) and hepcidin. Therefore iron overload associated with poor prognosis in HIV-1 infection could be partly caused by the viruses themselves [18
]. Plausibly, understanding the regulation of hepcidin production and how iron metabolism and viral infection interact may in the near future stimulate the development of new methods and strategies in the treatment and management of the disease.