A third of HAART-treated children had elevated lactic acid levels in a US study published in the July 4th edition of AIDS. Increased lactic acid levels did not cause symptoms, and were associated with an undetectable viral load, suggesting to the investigators that measuring lactic acid levels could be a useful measure of adherence in children.
Lactic acidosis is a rare, but potentially life-threatening side-effect of HAART and has been particularly associated with regimens containing ddI and d4T. It has been well described in adults, but until now no studies have looked at this side-effect of antiretroviral therapy in children.
Investigators from the Brooklyn Pediatric AIDS Network conducted a chart-review of 127 children to look for evidence of elevated lactic levels. A total of 251 lactic readings were obtained, from the 104 HAART-treated and the 23 treatment-naïve children who were aged between one and 17 years.
The overwhelming majority of the HAART-treated children, 102 (98%) were taking NRTIs as part of their therapy. The most common regimen was two NRTIs and a protease inhibitor, which was prescribed to 57 (55%) of children. The most commonly prescribed drugs were d4T, which 51 (49%) of children were d4T taking and ritonavir, which was taken by 38 (36.5%) of children.
Mean lactate levels were 1.7mmol/L (range 0.6 – 4.4mmol/L). Almost one third of the children had at least one reading over 2 mmol/L, and of the total of 251 lactate measurements 56 (25.6%) were over 2mmol/L. Treatment is not changed if lactate levels are below 5mmol/L, and none of the children in this study had a reading above 4.4mmol/L.
Only one patients became ill because of elevated lactic levels, experiencing abdominal pain and nausea and vomiting. No life-threatening cases of lactic acidosis occurred.
When the investigators examined that factors associated with elevated lactic levels they found that these included an undetectable viral load (below 400 copies/mL), irrespective of treatment regimen (p=0.01), NRTI therapy as a class (p=0.001) and treatment with a protease inhibitor (p=0.04). No significant relationship was found with d4T or ritonavir alone or in combination or with NNRTI treatment.
The investigators note, “the 32% prevalence of asymptomatic hyperlactatemia in our study is similar to that reported in adult literature” (8-35%).
Measuring lactic levels, could the investigators suggest, have a function in addition to checking for lactic acidosis, as “significantly in our study, elevated lactic levels were associated with an undetectable viral load irrespective of treatment regimen. Asymptomatic hyperlactatemia may serve as a surrogate marker for adherence in children on HAART”.
Although d4T was not associated with elevated lactic levels, treatment with protease inhibitors as a class was. Protease inhibitors have not been implicated as a cause of elevated lactic levels in adults and the investigators suggest that their data “raise the novel possibility that therapy with protease inhibitors may contribute to elevated lactate levels.”
Further information on this website
Lactic acidosis - overview
Lactic acidosis - factsheet
Desai N et al. Lactate levels in children with HIV/AIDS on highly active antiretroviral therapy. AIDS 17: 1565 – 1567, 2003.