Early antiretroviral treatment reduces seizure risk by two-thirds for children with HIV

Early antiretroviral therapy prevents the development of epilepsy in children with HIV, results of a study conducted in Botswana and published in the online edition of the Journal of Acquired Immune Deficiency Syndromes demonstrate. Starting treatment early reduced the risk of developing epilepsy by almost two-thirds.

The retrospective case-controlled study included children aged between 0 and 18 years who were infected with HIV at birth.

The investigators believe their findings have implications not only for the avoidance of seizures in HIV-infected children – in themself a significant cause of illness and death – but also for debates about the best time to start antiretroviral therapy.

Glossary

epilepsy

A condition where someone tends to have recurrent seizures (fits).

neurological

Relating to the brain or nervous system.

matched

In a case-control study, a process to make the cases and the controls comparable with respect to extraneous factors. For example, each case is matched individually with a control subject on variables such as age, sex and HIV status. 

CD4 cell percentage

The CD4 cell percentage measures the proportion of all white blood cells that are CD4 cells.

retrospective study

A type of longitudinal study in which information is collected on what has previously happened to people - for example, by reviewing their medical notes or by interviewing them about past events. 

They comment: “Our study suggests that neurological complications that may result from delaying treatment are potentially significant and should be considered.”

Infection with HIV increases the risk of seizures. Reasons include an increased risk of opportunistic infections, metabolic disturbances and neurological damage caused by uncontrolled HIV replication. Research from South Africa suggests that approximately 8% of HIV-infected children develop seizures, but studies involving adults have shown that antiretroviral therapy can reduce the prevalence of seizures from 17% in untreated patients to rates as low as 3% in individuals taking therapy.

There is ongoing debate about the value of early therapy for children with HIV. With these in mind, investigators from Botswana wanted to see early treatment reduced the risk of seizures for children under 18 years of age.

Early treatment was defined as:

  • Therapy in the first twelve months after birth.
  • Aged 1-5 years – therapy started when CD4 cell percentage was above  25%.
  • Aged five and over – initiation of therapy with a CD4 count above 350 cells/mm3.

A chart review was used to identify individuals experiencing seizures. They were matched on a 1:2 basis with age- and sex-matched controls who did not develop epilepsy (29 cases vs. 58 controls). Most of the cases were females (52%) and the median year of birth was 1998. All the cases and controls started antiretroviral therapy between 2003 and 2009; the most common combination was zidovudine, lamivudine and nevirapine.

Children who developed epilepsy were more likely to have a history of severe HIV-related illness (66% vs. 38%; p = 0.01) and severe immune suppression (59% vs. 29%; p = 0.01).

Overall, 45% of children started early treatment. Rates of epilepsy differed according to time of treatment initiation - 28% among those who started treatment early compared to 53% among those who did not.

Early treatment was associated with a 64% reduction in the risk of epilepsy (OR = 0.36; 95% CI, 0.14-0.92; p = 0.03). Starting treatment with a CD4 count above 500 cells/mm3 was associated with a further reduction in the risk of seizures (p = 0.05). In contrast, delayed treatment (CD4 cell percentage below 15% for younger children and CD4 count below 200 cells/mm3 for older participants) significantly increased the risk of seizures (p = 0.01).

In a third of cases, infections were the cause of seizures and in 27% of instances the development of epilepsy was attributed to the neurotoxic effects of HIV infection. No specific cause could be determined in the other cases.

“Our study adds to the growing body of literature that suggests that early identification and treatment of children with HIV is key to preventing neurologic complications in this vulnerable population,” conclude the authors.

References

Bearden D et al. Early antiretroviral therapy is protective against epilepsy in children with human immunodeficiency virus infection in Botswana. J Acquir Immune Defic Syndr, online edition. DOI: 10.1097/QAI0000000000000563 (2015).