Outcomes of paediatric antiretroviral treatment in resource-limited settings are promising, MSF shows

Medecins sans Frontieres research in 14 African and Asian countries shows that children in developing countries who receive treatment with non-nucleoside-based regimens similar to those recommended to adults experience remarkably good responses, regardless of the degree of immune system damage. The findings are published in the May 1^st edition of the journal Clinical Infectious Diseases.

The findings lend further weight to calls yesterday from the World Health Organization and UNICEF for a scale-up of HIV treatment for children in resource-limited settings.

In order to examine the links between initial immunosuppression and likelihood of survival after commencement of antiretroviral therapy, Medecins Sans Frontieres compiled antiretroviral treatment outcomes from 26 of its projects across ten African and four Asian countries. They found survival rates of 82% after 24 months, independent of the initial degree of immunosuppression.

A total of 586 children aged eighteen months to five years who had been on treatment for at least six months were enrolled. 97% were antiretroviral treatment-naïve; patients received cotrimoxazole prophylaxis according to WHO guidelines. Treatment courses varied somewhat, but all were standard WHO first-line non-nucleoside reverse transcriptase inhibitor (NNRTI) based regimens. Differences in regimen did not correlate with initial degree of immunosuppression, except that the profoundly immunosuppressed children were more likely to receive efavirenz.

Study participants were divided into three groups based on CD4 level at the start of treatment:

Median antiretroviral treatment length was 14 months, with no significant difference between groups.

Three-quarters of fatalities occurred during the first six months of treatment, with the median at 1.4 months. Children lost to follow-up (8%) were added to known deaths to calculate overall survival rates. No correlation was found between survival rates and degree of baseline immunosuppression, even after controlling for age, sex, malnutrition, previous antiretroviral exposure, and treatment regimen. Overall, probability of survival was 92% at six months, 89% after a year, and 82% after two years. These survival rates are comparable to those reported in studies with adults and older children.

The impact of the first twelve months’ antiretroviral treatment on immune recovery was assessed:

It is notable that these outcomes appear comparable to those achieved in resource-rich settings, though most published studies examine populations with significantly different characteristics to those of this study, with treatment-experienced older children using mainly protease inhibitor-based regimens.

Antiretroviral therapy is clearly effective in restoring many children to reasonable health, although it requires several months at least to return CD4 levels to the normal range, the authors note. During this recovery period immunosuppressed infants remain under threat from opportunistic infections.

Early HIV and CD4 testing to identify asymptomatic children with profound immunosuppression would need to be accompanied by education of parents and healthcare workers to ensure those at risk are tested, and by availability of affordable, accessible and competent antiretroviral treatment. In many contexts, asymptomatic children who are diagnosed by this means would also need protection against potentially life-threatening discrimination.

The study concludes that NNRTI-based antiretroviral therapy could restore health to many HIV-infected children in resource-limited settings, including those with the most serious damage to their immune systems.