Other than for oral candidiasis, there is a scarcity of literature on the rate of candidiasis (invasive or non-invasive) among HIV-infected children. This report is a retrospective study on an important part of follow-up of HIV-infected children in Spain. In our study, HIV-infected children were at increased risk of developing candidiasis (ICM and non-ICM) compared to the general population, but these rates, as with all opportunistic infections, declined with the widespread use of HAART. In addition, ICM was more infrequent than non-ICM among children of the general population as well as among children with HIV infection.
Poor cell-mediated immunity in HIV-infected children often results in opportunistic infections, especially in advanced stages of HIV infection
. The candida species is the most common cause of fungal infection among HIV-infected children
. However, HAART-derived immune reconstitution is an important protective factor against candidiasis infection
[19, 20]. The recovery of cellular immunity with HAART may partially reverse susceptibility to opportunistic infections when it achieves sustained undetectable levels of HIV-RNA and CD4+ levels above 500 cells/mm3 over a long period of time
[9, 11]. A high incidence of candidiasis diagnosis might be due to the lack of complete immune reconstitution and persistent CD4+ lymphopenia due to therapy failure
. The capacity of CD4+ recovery during long-term HAART in HIV-infected children with CD4+ levels below 5% is lower than in children with CD4+ levels from 5–15%, and restoration of the CD4+ cell percentage to a normal level is not necessarily achieved during long-term HAART
. Thus, continued surveillance of Candida infections may be important in order to assess the long-term effect of HAART on the occurrence of opportunistic infections in children.
Most candidiasis diagnoses were non-ICM and the rate of non-ICM diagnoses was higher in HIV-infected children than in HIV-uninfected children when children with hospital admissions were compared. However, these data should be interpreted with caution because they refer to primary and secondary diagnoses among children with hospital admissions. Since it is very rare for an HIV-uninfected child to be admitted to a hospital because of non-ICM such as oral candidiasis, the rate of non-ICM in HIV-uninfected children may be underestimated, as the database comes from hospital admissions only. Additionally, the rate of non-ICM children with hospital admissions decreased during follow-up, but no significant values were found. However, when we analyzed the data by children living with HIV/AIDS, the non-ICM rate decreased significantly in the last calendar period (2003–2008), reaching values similar to those of other pediatric populations infected with HIV
[11, 18, 22]. This may be due to the extensive use of HAART and improved immunosurveillance, which is an important protective factor against candidiasis
[19, 20]. In addition, advances in HIV treatment, earlier diagnosis of infection status in exposed infants, and quantitative monitoring of virology and immunologic parameters may also have contributed to decreases in candidiasis rates. Moreover, the earlier HIV treatment starts over time, as per PENTA guidelines
, the more non-ICM will be prevented.
Most ICM in children occur in the hospital setting, and this type of candidiasis is generally seen in severely immunocompromised persons such as cancer, transplant and AIDS patients, as well as nontrauma emergency surgery and critical ICU patients
. ICM is a leading cause of nosocomial mycosis with a high associated mortality
. In our study, HIV-infected children with ICM diagnoses had longer hospital stays than children with non-ICM diagnoses, indicating that ICM diagnoses would appear in children with more serious clinical events and suppressed immune systems
. Moreover, our data show that HIV-infected children were at increased risk of developing ICM, although the ICM rate decreased during the follow-up. Thus, ICM rate in the last calendar period (2003–2008) was not higher in HIV-infected children than in the general population according to our study and other reports published
[17, 25, 26]. Therefore, it is not as important of a health problem among HIV-infected children in the last years of the HAART era.
This study had several limitations that may impact our findings. This work was a retrospective study and we had no access to patient clinical data (antiretroviral treatment regimen, duration of HAART, CD4+ count, HIV viral load, CDC stage) that might have affected our results. MBDS data are anonymous and it is impossible to identify whether a patient has been hospitalized at different hospitals within the same calendar year. This may have caused a slight overestimation of our results because we may have calculated disease exacerbations or remissions as new participants. We cannot know the total number of HIV-infected children in Spain at present, because there is no national coverage data of HIV diagnoses of children in Spain. We used an estimation of the number of HIV-infected children in Spain, which was calculated from two reliable databases (Spanish National AIDS Register and Madrid Cohort HIV Children).