SHM research focus: Long-term outcomes of children treated for HIV infection
Sophie is will be defending her PhD thesis on 16 October 2015.
Background
Over the last thirty years, combination antiretroviral therapy (cART) has changed HIV from a fatal disease to a chronic, treatable condition. Before adequate treatment was available, nearly half of untreated perinatally HIV-infected children died before their second birthday. Today, however, providing they receive timely cART, these same children not only survive, but are growing up to become adults who can participate fully in society.
Unfortunately, it is becoming increasingly evident that even well-treated HIV-infected children are more vulnerable to problems that may adversely affect the development of their brains and other organs. Furthermore, these patients also carry the burden of daily medication and the associated side effects, as well as the persisting stigma associated with HIV infection.
To better understand the effect of cART in HIV-infected children, my PhD research examined the long-term response to cART in the HIV-infected paediatric population in the Netherlands and investigated various complications associated with chronic HIV infection in children.
Epidemiology of HIV-infected children in the Netherlands
The first part of the thesis describes the epidemiological data of all HIV-infected children in the Netherlands who have been registered and monitored by SHM since 1996. The majority of these children are (first-generation) immigrants from endemic regions, in particular sub-Saharan Africa (SSA). This Dutch HIV-infected paediatric population was found to have good long-term immune recovery after starting cART, regardless of the age at the time of starting cART or baseline CD4+ T cells. Moreover, the proportion of children with an undetectable HIV load rose from 27% in 1996 to 89% in 2012 and, as such, is one of the highest in developed countries.
We also examined the differences between HIV-infected children born in the Netherlands and those who immigrated from SSA to the Netherlands after birth. Although diagnosis and start of cART was later in the SSA group, there was no difference in immune recovery in the long term, and both groups had a comparable virological response.
Complications in HIV-infected children: cognitive function
As well as the above-mentioned epidemiological studies, we looked at various complications associated with chronic HIV in children, including neurological and cognitive function in children with perinatal HIV infection. All historical HIV and cART-related data came from SHM’s dataset. An essential feature of this study was the inclusion of a comparable healthy control group. Our results showed that, despite generally adequate and long-term treatment in the majority of the HIV-infected group, children in this group had poorer cognitive function than healthy controls. In addition, we found that a poor CDC clinical status at HIV diagnosis was associated with a lower IQ.
Furthermore, brain imaging using 3 Tesla Magnetic Resonance Imaging (MRI) revealed that children with HIV had a lower volume of grey and white matter, more white matter abnormalities and lower white matter integrity. We also found associations between poorer CDC category prior to starting therapy, lower brain volume and poorer white matter integrity. In addition, some of these MRI abnormalities correlated with poorer cognitive function.
Complications in HIV-infected children: fat distribution
We also looked at changes in regional fat distribution in a longitudinal study of two paediatric cohorts from the Netherlands and South Africa, using dual-energy X-ray absorptiometry (DEXA). Here too, for the Dutch group, SHM provided detailed data on cART regimens, thereby allowing us to accurately analyse exposure to various antiretroviral medications, as well as the number of months of exposure to each cART regimen. This study showed that subcutaneous fat loss still occurs in HIV-infected children and that this fat loss is markedly associated with the use or prior use of the antiretroviral agent, stavudine. This side effect is the main reason why stavudine is no longer recommended by the World Health Organisation; nonetheless, it is still prescribed in many developing countries.
The results of our research show that, although treatment of HIV in children is effective in terms of survival, there remain various, and in some cases, serious complications. These complications may impede HIV-infected children when they grow up into adults who have to participate in society. For this reason, our research remains ongoing and is currently looking into the pathophysiological background to the problems observed in the HIV-infected group. The results should form the basis of new strategies to prevent and/or treat the complications of treated HIV in children. SHM’s data will once again be necessary in these ongoing studies and my successor, Charlotte Blokhuis, will be making regular (virtual) visits to SHM!
With thanks…
The SHM database has been invaluable in our work and has played a major role in the generation of data for all my PhD research. In particular, I am extremely grateful to Colette Smit, who has been involved right from the start of my PhD.
I myself will be embarking on a paediatrician’s training at the EKZ and I hope to continue working with SHM for a long time to come!