Changes in the epidemiological characteristics of paediatric patients with HIV infection in Navarre  

INTRODUCTION

The routine use of highly active antiretroviral therapy (HAART) during pregnancy and delivery in women infected by human immunodeficiency virus (HIV) and in newborns from the first hours post birth, introduced in 1997, has resulted in a substantial decrease in the vertical transmission of this virus, which is the main source of paediatric HIV infection.¹ This approach resulted from the women and infants transmission study of the AIDS Clinical Trials Group (ACTG) Protocol 076, which found a drastic decrease in the vertical transmission of HIV, and is therefore considered one of the great advances in the treatment and prevention of the HIV pandemic.²

The World Health Organization (WHO) has established the prevention of vertical transmission of HIV through the treatment of pregnant women and their newborns as one of the millennium development goals.³ However, there is high variability in the access to antiretroviral treatment in the worldwide population, and therefore it has not been possible to achieve this goal at the global scale.

In our autonomous community of Navarre, Spain, the phenomenon of immigration, which has increased in the past decade, has resulted in an increase in the subset of the population that originates from countries where the prevalence of HIV infection is much higher compared to Spain.⁴

The decrease in the number of new cases in native Spaniards combined with the increase of immigrants from countries with high HIV infection rates has given rise to epidemiological changes in the cases of children infected by HIV by vertical transmission in Navarre in the past 10 years. The main objective of our study was to describe this epidemiological shift.

A secondary objective was to review the approach to the treatment of patients with HIV, which has improved significantly with the introduction of combined pharmacotherapy and advances in antiretroviral drug development.

MATERIALS AND METHODS

We conducted a retrospective study by reviewing the health records of children infected by HIV managed at the Paediatric Infectious Disease Unit of a tertiary hospital in Navarre, which is the reference centre in this autonomous community. We collected epidemiological, clinical and treatment data.

We defined migrant children as children born in a country other than Spain or with at least one parent born in another country that had resided in Spain for less than 10 years. We analysed origin by geographical region and country.

The follow-up period lasted 15 years. To analyse temporal trends, we divided this period in three 5-year intervals (A: 2000-2004, B: 2005-2009, C: 2010-2014).

We used the SPSS^® software to perform the analysis. To calculate rates, we used the data on incidence and prevalence published by the Instituto Nacional de Estadística (National Institute of Statistics) and data for the paediatric population in different autonomous communities.

RESULTS

We identified 15 new cases of paediatric HIV in Navarre diagnosed between 2000 and 2014. There was a decrease in incidence with time, from 8 cases in 100 000 inhabitants in period A (2000-2004), to 4/100 000 in period B (2005-2009) and 4/100 000 in period C (2010-2014).

When we analysed the geographical origin of the cases, we found no differences overall: 8 cases were diagnosed in native Spanish children (53.3%) and 7 in migrant children (46.6%). However, when we compared origin in the different time periods, we found significant differences: in period A (2000-2004), 100% of cases were diagnosed in children of native Spanish mothers, while in periods B and C, 100% and 75% of newly diagnosed cases, respectively, occurred in children of migrant mothers.

When it came to the geographical location where transmission had occurred, we found that all children that received a diagnosis of HIV infection in period A had been born in Spain. However, thanks to the routine use of preventive measures, only one case of vertical transmission was documented in child born in Spain after period A (in 2005), corresponding to a mother that had acute HIV infection during pregnancy. From this moment on, all new cases occurred in children born in another country who were found to already have the infection at the time they arrived in Spain. Of these children, 57% came from Sub-Saharan Africa, 29% from Central America and 14% from Eastern Europe.

As we mentioned above, all children in the sample had acquired HIV infection by vertical transmission. However, we did differences in the mode of transmission in mothers. In period A, 86% of mothers had acquired the infection through intravenous drug use (IVDU) and the remaining 14% by heterosexual transmission. There were no cases in which mothers had been infected through IVDU since 2009. In period B, all new cases corresponded to children of mothers that had acquired the infection through heterosexual transmission, and in period C the mode of transmission in the mother was heterosexual transmission or unknown. We found no cases of HIV transmission through transfusion.

Another factor in which we found changes over time was the main carer of the child with HIV. In 2004 (period A) 2 out of every 7 children (28%) were in the care of institutions or in foster care, while the rest were in the care of their biological parents or close relatives. At the end of 2014 (period C), only 8 out of 15 (53%) children were in the care of family members, while the rest were in foster care families (27%) or institutions (20%).

We did not find statistically significant differences in the clinical and immune status of patients based on the stage at diagnosis. Of the 15 children in our sample, 9 received the diagnosis when they were at stage A1, 3 when they were at stage A2, 1 at stage B1 and 2 at stage B2. One of the patients died during the acute phase of infection. In all the remaining patients, an undetectable viral load had been achieved by the end of the study.

The last aspect that we assessed were changes in treatment. Owing to combined pharmacotherapy, we found a significant decrease in the number of drugs required for the management of HIV infection. At the beginning of the study period, patients were taking more than 10 drugs a day, compared to only 1 a day at the end of followup.

DISCUSSION

Navarre is a region with a low prevalence of paediatric HIV, which has remained stable in the past 10 years. The infectious diseases unit of our hospital manages 100% of the paediatric patients with HIV in this autonomous community, so despite the small size of our sample, the conclusions drawn by our study represent the actual situation. Our findings reflect the sociodemographic changes that have taken place in Navarre during the period under study, in which the main factor at play was migration⁵.

In Spain, as in other developed countries, the incidence of infection by HIV has decreased in the past 15 years. In the paediatric population, in which transmission is mainly vertical, this decrease is mainly due to the introduction of universal screening of pregnant women, treatment during pregnancy and prophylactic treatment in pregnant women and newborns.^4,6 There is evidence that antiretroviral therapy in women before pregnancy is the most successful strategy for the prevention of HIV transmission to children, as it improves the clinical and immune status and reduces the viral load in mothers.⁴. Indeed, we found no cases of vertical transmission in children in Navarre after the introduction of HAART with the exception of 1 case in 2005 in a child whose mother had acute HIV infection during pregnancy and in whom, despite initiating appropriate treatment, transplacental infection could not be prevented.

When it comes to the phenomenon of immigration in Navarre, there has been an increase in the number of foreign-born residents in the first decade of the XXI century, consistent with the rest of Spain.⁶ Thus, in 2014 the resident aliens registered in the census of this autonomous community amounted to 10.2% of the total population. The number of children born to mothers of foreign nationality amounted to 2.5% of the total births. However, the children of foreign parents that were born in Navarre benefitted from the implemented preventive measures, as the new cases in the last years of our study occurred in children that had been born in the country of origin and subsequently migrated to Spain.

As was the case in previous studies, the most frequent geographical origin of HIV-infected children was Sub-Saharan Africa, followed by different areas in Latin America, due to the high incidence of disease in these regions. When it came to the mode of transmission in mothers, we found a shift in the pattern of infection, with heterosexual transmission replacing IVDU as the leading source of infection.⁵ This may be explained partly by the phenomenon of immigration and partly by the decrease in the number of injectable drug users combined with the introduction of measures to prevent transmission between them.

A salient finding in our study was the change observed through time in the main carers of HIV-infected children, with an increase in the percentage of these children that are in foster care or institutionalised.

We did not find differences between migrant and native Spanish children in clinical status at the time of diagnosis or during followup. This is due in part to early detection at the primary care level and the routine screening of pregnant women, which result in the homogeneous management of infection.

Lastly, we want to highlight the changes that have occurred in antiretroviral therapy, as we consider that the drastic decrease in the number of medications that need to be taken each day is a factor that promotes adherence to treatment and improves the quality of life of patients with no detriment to their health.

To conclude, we found that the overall frequency of new cases of HIV infection in children has decreased in recent years, with an increase in the proportion of cases diagnosed in foreign-born children, especially from Sub-Saharan Africa. Our study confirmed the importance of serologic screening of children that immigrate from high-prevalence countries and routine screening of pregnant women to reduce the morbidity and mortality associated with HIV infection to the extent possible.

CONFLICTS OF INTEREST

The authors have no conflicts of interest to declare in relation to the preparation and publication of this article.

ABBREVIATIONS

HAART: highly active antiretroviral therapy • HIV: human immunodeficiency virus • IVDU: intravenous drug use • WHO: World Health Organization.

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