A large number of stable, HIV-infected children were anaemic. Few had severe anaemia. Furthermore, both the proportion of children with anaemia and median haemaglobin concentration were associated with clinical and immunological status. There was no association between Hb and chronological age. Studies of infected children and adults indicate that anaemia independently predicts poor outcome [2, 14, 15]. The results of the present study are in agreement with these observations, as significantly more children with severe clinical features and severe immunosuppression were anaemic.
Many children had abnormal red blood cell morphology. Anisocytosis was the most frequent observation. It usually correlates with an increased red blood cell distribution width , present in many children. Anisocytosis is a non-specific feature that may be present in any red blood cell disorder, including IDA and ACD . Interestingly, there was a statistically significant relationship between disease status and red blood cell morphology. More children with severe clinical disease and severe immunosuppression had abnormal morphology. These findings were similar to the relationship between disease status and anaemia, and reflect the connection between abnormal morphology and anaemia.
Distinguishing IDA from ACD in chronic inflammatory diseases may be a problem, as many of the laboratory measurements used to evaluate iron status are affected in a similar manner . Ferritin concentration remains the most practical measurement for evaluating iron stores. A low concentration (< 10 μg/L) unequivocally identifies iron-depleted stores. Ferritin is an acute phase reactant. Therefore, levels may be falsely normal in chronic inflammatory diseases such as HIV infection, despite the presence of iron depletion [12, 13]. Elevated ferritin levels, often exceeding 1000 μg/L have been recorded in adults with acquired immunodeficiency syndrome . In the present study, 45% (20/44) of all anaemic children were iron-depleted. A comparison of the laboratory results of anaemic children with or without hypoferritinaemia (Table II) showed few statistically significant differences between the two groups. In particular, sTfR was not significantly different between the two groups. Failure to show a clear distinction between these groups confirms the complex relationship between iron depletion, iron deficiency anaemia and anaemia of chronic disorders in HIV infection.
The present study employed strict criteria to identify children with IDA. These criteria were adapted from previously published guidelines. Although locally derived normal age-related values were taken into consideration the criteria were similar to those used internationally [12, 13]. The results probably under-represent the true extent of IDA. For example, only four children with microcytic, hypochromic anaemia had low ferritin concentrations. They were included in the IDA group. The other three with microcytic, hypochromic anaemia were excluded, although they had significantly elevated soluble transferrin receptor concentrations, in keeping with IDA (Table III). Despite these omissions, the results suggest that IDA is more prevalent in HIV-infected children than in the general paediatric population in South Africa .
Soluble tranferrin receptor is not an acute phase reactant. It is considered more reliable than ferritin to distinguish IDA from ACD in acute and chronic inflammatory diseases. In IDA sTfR is elevated and in ACD sTfR remains normal [13, 18]. In the present study, sTfR of anaemic children with or without hypoferrritinaemia were not significantly different. However, those with microcytic, hypochromic anaemia had significantly elevated sTfR. The results suggest that many HIV-infected children with anaemia probably have a combination of ACD and iron depletion, a smaller proportion have IDA and some children with normal ferrritin concentrations have IDA. Only those with classic findings of IDA had predictably high soluble transferrin receptor concentrations.
The biggest weakness of the present study was the failure to compare the iron status of HIV-infected children with non-HIV-infected controls. However, iron depletion was widespread, and IDA was far more prevalent than was documented in a recent national study of more than 6000 South African children . That study was undertaken in 1994, when the prevalence of paediatric HIV infection was low . The findings of the present study were comparable to results obtained in an Italian study evaluating iron status in HIV-infected children. In the Italian study iron deficiency, defined as low serum iron concentration, was present in 48% of HIV-infected children. The present study employed stricter criteria to define iron status. Therefore we can conclude that iron depletion and IDA are significant problems in HIV-infected children in South Africa.
Many aetiological factors probably contribute to the development of low iron status in HIV-infected children, including reduced dietary intake, the quality of dietary iron and altered iron absorption . The Italian study showed that intestinal malabsorption is a major factor . Whether iron therapy causes deleterious effects in paediatric HIV infection has not been established. In general, while the relationship between infection and iron status remains contentious, iron overload is associated with increased susceptibility to certain infections . Therefore, liberal iron therapy or prophylaxis in HIV-infected children may facilitate the development of opportunistic infections. For the present time, HIV-infected children with IDA should receive therapeutic iron replacement. However, more research is required to establish the benefits and or deleterious effects of iron therapy and prophylaxis in antiretroviral naive, HIV-infected children, particularly those with iron depletion.