Poor weight gain during first year of ART associated with increased mortality risk for children with HIV in resource-limited settings

Poor weight gain after starting antiretroviral therapy (ART) is associated with increased mortality risk for children with HIV, investigators report in the online edition of AIDS. An international team of researchers developed a model to examine the association between weight gain and mortality risk for children starting ART. Poor weight gain was associated with increased mortality risk, independent of other factors.

“We were able to construct normative reference standards for weight gain at 6, 12, 18, and 24 months of ART for HIV-infected children younger than 10 years,” write the authors. “At 6 and 12 months on ART, the hazard of dying in children whose weight gain was below the 33rd percentile was at least twice that of children who gained more weight.” The investigators hope their model will be useful in resource-limited settings where access to CD4 count and viral load testing – key assessments of the success of ART – is limited.

An estimated 3 million children are living with HIV and 90% live in sub-Saharan Africa. Without ART, half of these children will die before their second birthday.

Glossary

hazard

Expresses the risk that, during one very short moment in time, a person will experience an event, given that they have not already done so.

epidemiology

The study of the causes of a disease, its distribution within a population, and measures for control and prevention. Epidemiology focuses on groups rather than individuals.

virological suppression

Halting of the function or replication of a virus. In HIV, optimal viral suppression is measured as the reduction of viral load (HIV RNA) to undetectable levels and is the goal of antiretroviral therapy.

Access to ART is expanding in poorer countries, but because of cost CD4 and viral load monitoring is often unavailable. Other measures are therefore needed to assess the effectiveness of treatment.

Weight gain during the first year of ART has been shown to be a good predictor of treatment success for children in Africa during the first year of therapy. However, gains in weight that correlate with specific treatment outcomes are unknown.

Investigators therefore examined data from the International Epidemiological Database to Evaluate AIDS for 7173 children younger than ten years living in resource-limited settings. Using this, they constructed a model to establish the associations between age- and sex-specific weight gains (3rd, 10th, 25th, 33rd and 50th percentiles) and mortality risk, virological suppression and risk of virological failure at 6, 12, 18 and 24 months after ART initiation.

Over half (51%) the children lived in southern Africa, approximately a quarter in eastern Africa, 13% in Asia, 9% in western Africa and 4% in central Asia.

The majority of children (78%) started ART between 2005 and 2007. At the time treatment was initiated, 45% were underweight. Baseline CD4 cell measurements were available for 72% of children, and three-quarters were severely immune-suppressed at this point.

The children were followed for a median of 24 months, and during this time there were 111 deaths. Most (61%) occurred between months six and twelve of treatment initiation.

Children with poor weight gain after six and twelve months of ART had a higher risk of death compared to children with good weight gain. Children below the 33rd percentile of weight gain had a threefold increase of death at month six (HR = 2.95; 95% CI, 2.03-4.36) and an over twofold increase in mortality risk at month twelve (HR = 2.28; 95% CI, 1.23-4.22). The mortality risk was even higher for children with lower weight gains, especially in the first twelve months of therapy. The increased risk of death associated with poorer weight gain persisted up to 24 months of follow-up.

However, no significant association was found between weight gain and virological suppression or risk of virological failure.

“Monitoring weight gain post-ART using normative data developed specifically for HIV-infected children on ART could be a simple and highly valuable tool to identify those children at highest risk of death,” conclude the investigators.

References

Yotebieng M et al. Age-specific and sex-specific weight gain norms to monitor antiretroviral therapy in children in low-income and middle-income countries. AIDS 28, online edition. DOI: 10.1097/QAD.0000000000000506 (2014).