Children with HIV infection show the best immune system recovery if HIV treatment is started before they are five months old, according to an observational cohort study published in the 1st April edition of The Journal of Infectious Diseases.
Despite almost 15 years of experience in treating HIV-positive children, doctors are still uncertain about the best time to start treatment. As in adults, HIV treatment has the advantage of preventing the progression of disease, but this must be balanced against the drawbacks of side-effects, the development of drug resistance and the need for high levels of adherence and lifelong treatment.
The decision on when to start treatment in children is made more complicated since few studies have assessed the effect of age on treatment responses. In addition, CD4 cell counts of children change as they get older, making it difficult to compare the response to treatment in different age groups.
To understand the relationship between age and HIV treatment better, investigators from the European Collaborative Study examined the response to treatment in 131 HIV-positive children who had contracted HIV from their mothers. After correcting the CD4 cell count response for each child’s age, they found that starting treatment before five months of age resulted in a better treatment response. However, the sustainability of the CD4 cell count response was not affected by how old the children were.
“Our results suggest that there is benefit in initiating antiretroviral therapy early, soon after HIV diagnosis,” the investigators conclude. “Our findings also suggest that the likelihood of sustaining an immunological response was not dependent on age at initiation.”
The European Collaborative Study has collected data on HIV-infected children at eleven paediatric centres in nine European countries since 1986. In this study, 42 (32%) of the children were infected before 1990, but only six (5%) were infected after 1999.
Because the study was started before the introduction of highly active antiretroviral therapy (HAART), 39 (30%) of the children were treated with single- or dual-drug combinations, while another 55 (42%) started with single- or dual-drug treatment before switching to HAART. The rest of the children took HAART with no prior HIV treatment. The children began their most potent treatment combination at a median age of four years.
The investigators found that the children starting treatment before five months were more likely to achieve a 20% increase in age-adjusted CD4 cell count than those starting between five months and five years of age (adjusted hazard ratio [AHR] = 0.37, p
They point out that this is equivalent to treatment during ‘primary infection’. Some experts believe that treatment during the first few months after infection leads to better treatment response, since HIV has had less opportunity to damage the immune system. This is supported by another recent study, which found that children's responses to treatment were better when it was started before HIV had damaged the immune system irreversibly.
In addition, the investigators explain, younger babies have greater production of new T-cells in the thymus gland than older children. This could allow their CD4 cell counts to recover more fully once HIV treatment has started.
The investigators also found links between response to HIV treatment and both ethnicity and the type of HIV treatment. Black children had a poorer response to treatment (AHR = 0.48, p = 0.01), as did those who were treated with single- or dual-drug therapy compared with those who took HAART. This was true for those who switched to HAART from one or two anti-HIV drugs (AHR = 3.16, p
In contrast, the CD4 cell count at six months after starting HIV treatment was not affected by age or race. At this stage of treatment, HAART without any prior anti-HIV treatment was associated with a higher CD4 cell count (AHR = 1.08, p = 0.02). Treatment response in the first six months was also linked to the CD4 cell count and to the stage of HIV disease when treatment was started.
“Black children [followed] a similar trajectory to that of white children during the first eight months of therapy,” the investigators explain. “However, black children were more likely than white children to initiate HAART without prior receipt of antiretroviral therapy and to do so before five months of age.”
This study's conclusions are limited by its small sample size and observational design. “Our conclusions are based on data from a prospective observational cohort, which raises the problems of potential selection bias and temporal changes in the therapeutic management of HIV disease,” the investigators write.
“Although we adjusted for the timing of therapy and prior antiretroviral therapy use, our findings are limited by the relatively small numbers of children in the youngest age group,” they add. “However, in the absence of randomised trials to evaluate the effectiveness of earlier versus later initiation of antiretroviral therapy, our findings contribute to the evidence base.”
European Collaborative Study. CD4 cell response to antiretroviral therapy in children with vertically acquired HIV infection: is it associated with age at initiation? J Infect Dis 193: 954 – 962, 2006.