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ICAAC: High mortality rate from symptomatic lactic acidosis in Thailand
Michael Carter & Derek Thaczuk, Monday, September 17, 2007
Lactic acidosis led to the death of 7% of Thai patients presenting with symptoms of the condition, according to a retrospective study presented this week at the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy in Chicago. Individuals with low body weight were at highest risk of death.

Lactic acidosis is a rare, but potentially fatal side-effect of some nucleoside reverse transcriptase inhibitor (NRTI) drugs.

To date, there have been limited data regarding the incidence and risk factors for death from lactic acidosis amongst patients who develop the condition, particularly in resource-poor settings.

Thai investigators therefore conducted a retrospective study of 125 antiretroviral-treated patients who were diagnosed with symptomatic lactic acidosis between 2004 and 2006. The diagnosis required lactic acid levels of 2.5 mmol/l or above in their blood, plus clinical symptoms, the most frequent of which were nausea, vomiting, difficulty breathing, abdominal pain, muscle weakness and sensory impairment.

Patients were followed for three months after the diagnosis of the condition. The mean age of patients who developed the condition was 40 years, 61% were male, mean body weight was 58kg and median CD4 cell count was 161 cells/mm3.

Unsurprisingly, nucleoside analogue (NRTI) use was associated with lactic acidosis. The very widespread Thai use of d4T (stavudine) was reflected in this cohort, with 114 (91%) taking d4T (stavudine), five (4%) ddI (didanosine) plus d4T, four (3%) AZT (zidovudine) plus ddI, and two (2%), ddI. Median duration of antiretroviral therapy before the diagnosis of lactic acidosis was thirteen months.

Nine (7%) of the 125 patients died. At the time lactic acidosis was diagnosed, the patients who later died had higher mean lactic acid levels (8mmol/l vs. 5mmol/l) and higher mean ALT scores (164u/l vs. 48u/l) than the patients who survived. Both these differences were statistically significant (p < 0.003). The patients who died also had lower mean body weight (48kg vs 59kg, p = 0.008).

The investigators identified the following as significant indicators of risk of death: body weight below 45kg (odds ratio [OR] 9.09, 95% confidence interval [CI], 1.575 – 52.632, p = 0.014) and lactic acid in blood above 10mmol/l (OR, 20.372, 95% CI, 2.610 – 159.001, p = 0.004).

They conclude, the “mortality rate of symptomatic hyperlactatemia among HIV-infected patients receiving antiretroviral therapy is substantial. The patients who had low body weight and high serum lactate level are at higher risk of mortality.” They suggest that “early diagnosis needs a high level of [clinical] suspicion.”

A recently published Ugandan study found a high incidence of lactic acidosis amongst patients taking fixed-dose anti-HIV therapy. Treatment with d4T was identified as being the major risk factor for the development of lactic acidosis and the investigators recommended that AZT, rather than d4T should be used for first-line anti-HIV therapy in resource-limited settings.

Reference

Manosuthi W et al. Mortality rate and risk factors of death in symptomatic hyperlactatemia among HIV-infected patients receiving antiretroviral therapy. 47th Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, abstract H-375, 2007.