Background: In Malawi, >100,000 patients have been started on first-line ART with stavudine (d4T)/lamivudine (3TC)/nevirapine (NVP). Given long-term use of d4T, increasing cases of lactic acidosis can be expected. As lab resources are limited in Malawi, accurate characterization of the clinical presentation is critical to diagnosis in the Malawian setting.

Methods: Lighthouse clinic is a HIV clinic at the Kamuzu Central Hospital (KCH) in Lilongwe and a referral site for central region ART clinics. UNC project provides laboratory support to the Lighthouse and KCH. Since 2001, 7772 patients have been started on d4T/3TC/NVP at Lighthouse. We retrospectively reviewed the hospital, clinic, and lab files for demographics, clinical course and laboratory values of patients in whom a lactic acidosis diagnosis was suspected from October 1, 2004 until July 30, 2007. Frequencies, means, medians, and tests of associations were determined as appropriate. Confirmed lactic acidosis cases had lactate >3.5 mM/L.

Results: We reviewed 236 suspected lactic acidosis cases (73% women). Of suspected cases, 64% were Lighthouse patients and 36% were referrals. In 121cases (51%), hyperlactatemia was confirmed. However, in 115 cases, the diagnosis was excluded. Confirmed cases were more likely to have higher baseline weight (63 kg vs 54 kg, p <0.001), higher peak weights (71 kg vs 61 kg, p <0.001), vomiting (63% vs 41%, p <0.001), and weight loss (82% vs 61%, p <0.001). Among confirmed cases, median age was 39 years, median duration of ART was 439 days (IQR 340 to 695) and the median increase in CD4 on ART was 183 cells (IQR 56 to 293); 97% patients had at least 1 gastrointestinal symptom (nausea, vomiting, anorexia, abdominal distension); 93% had neuropathy; and 82% had weight loss (median loss 6.4 kg, IQR 4 to 10). The mean lactate level was 6.5 mM/L (range 3.6 to 15); 7 patients died. Among survivors continuing care at the Lighthouse (n = 69), most were switched to AZT/3TC/NVP (66%). Patients resumed ART after a mean of 79 days (range 0 to 1141 days).

Conclusions: Clinical diagnosis of lactic acidosis was not specific. Among confirmed cases, gastrointestinal symptoms, weight loss, and high baseline and peak weights were associated with a diagnosis of lactic acidosis. However, given lack of specificity, programs should provide the necessary laboratory equipment for monitoring drug toxicities, at a minimum, in referral settings to avoid unnecessary stops of ART and correctly identify toxicity rates.