Our study found a high prevalence of anaemia among HIV-infected paediatric patients presenting at an urban HIV clinic in Uganda, majority of them with mild anaemia. The frequency as well as severity of anaemia correlated with advanced clinical and immunological HIV disease stage. The study also found a significant association between the presence of anaemia and a poorer short-term virologic response to HAART.
Anaemia in HIV-infected children is multi-factorial and takes varying morphological types
[19, 20]. As in several other similar studies, we found microcytic-hypochromic anaemia to be the commonest type, especially in advanced HIV disease stages. Although this study did not do specific tests for iron status, it can be expected that iron depletion could have contributed to the high proportion of microcytic-hypochromic anaemia. Alternatively, anaemia of chronic disease – in this case due to advanced HIV disease and related co-morbidities - has also been known to present a similar morphological picture. Another well studied cause of anemia in adults is the presence of antibodies to endogenous erythropoietin
. This in children has not been studied.
Although the mean reticulocyte count was significantly higher among patients who were anaemic at baseline, about 25% of these patients had a normal or low reticulocyte count at baseline suggesting either bone marrow suppression as the cause or, at least, a sub-optimal bone marrow response to the anaemia.
In this study, advanced HIV clinical stage
 was found to be independently associated with the presence of anaemia at baseline. In fact, almost all anaemic patients in early HIV disease stages had mild anaemia; moderate and severe anaemia was found exclusively among patients in stages III and IV. Similarly, the CD4% was significantly associated with the likelihood of anaemia, even after controlling for WHO clinical stage. This association between anaemia and advancing HIV disease has been reported previously
[7, 9, 23] and could be explained by the increasing viral burden which may cause anaemia through increased cytokine-mediated myelosuppression, and/or a higher burden of co-morbidities.
As would be expected from previous studies
[24, 25] most patients showed significant clinical, immunological and virological response to ART, including those with advanced or severe HIV disease. Notably, a significant proportion of children with anaemia at baseline showed improvement in haemoglobin and related haematological indices while on ART, even without specific additional treatment targeting anaemia. This observation has been reported previously and reinforces the suggestion that a proportion of these cases of anaemia were related directly to chronic HIV infection
Virological response, however, was significantly better among non-anaemic patients compared to those with anaemia, especially in the first 3 months on ART. Compared to initially anaemic patients, non-anaemic patients achieved a higher mean reduction in viral load and a significantly higher proportion attained complete viral suppression. Several previous studies have highlighted the importance of anaemia as an independent prognostic factor in HIV-infected individuals. Anaemia increases the risk of progression to AIDS
[8–10] as well as the risk of death in HIV infected patients, both in cross-sectional
 and longitudinal studies
[8, 9, 23]. The adverse long term outcomes more likely reflect anaemia as a proxy of more advanced disease.
In this study we focused on the more immediate outcomes of treatment with antiretroviral drugs, i.e. viral suppression, rise in CD4+ counts and short-term clinical improvement. Our findings, while reaffirming the importance of anaemia as a poor prognostic factor in HIV-infected children, suggest that the observed poorer outcome in anaemic HIV-infected children is, at least in part, mediated by a suboptimal virological response to HAART. The mechanism of the blunted virological response observed in anaemic children is not clear. Our study enrolled only ART-naïve children and did not include testing for viral resistance to antiretroviral drugs. It is possible that anaemic children who did not respond adequately to ART harboured some drug resistant strains; the risk of this could be expected to be higher in relation to the higher baseline viral loads observed among anaemic children. Other mechanisms might relate to possible poorer bioavailability of drugs in the sicker, anaemic children.
Regardless of the mechanism, recognition of anaemia at initiation of ART could be useful to alert clinicians to children requiring closer monitoring for possible treatment failure. Furthermore, since correction of anaemia has been shown to improve prognosis, monitoring of haemoglobin during ART should help identify those children whose anaemia does not quickly respond to ART and thus require further investigation and specific treatment to correct anaemia.
Results of this study need to be interpreted cautiously in light of some important limitations. Firstly, the exact causes of anaemia in these patients were not determined. A causal relationship should not be inferred about the association between anaemia and ART response, however using our multiple regression analysis, anemia remained a significant predictor of virological response. Secondly, the lack of data on anaemia in a comparable group of HIV negative children in the same setting limits our ability to interpret the prevalence results. Thirdly, failure to achieve sample size for the cohort due to limited time may have affected the results of the effect of baseline anaemia on subsequent effect on response to ART. However, the prospective cohort design, with longitudinal data collected suggests that the association between anaemia and ART response warrants further study in a larger cohort.