Severe Hyperlactataemia Complicating Stavudine First-Line Antiretroviral Therapy in South Africa

Abstract

Background In the public sector antiretroviral therapy (ART) programme in South Africa the standardized first-line regimen includes stavudine (d4T). Severe symptomatic hyperlactataemia (SHL) is a potentially life- threatening complication of d4T. Methods GF Jooste Hospital is a referral centre for six ART clinics. We retrospectively reviewed cases referred with lactate levels ≥5 mmol/l that were attributed to nucleoside reverse transcriptase inhibitors from August 2003 to November 2005. We calculated cumulative ART exposure in patients attending these clinics to derive a referral rate. Results In total, 75 patients were referred with severe SHL (71 female). All had been on d4T and on ART for a median of 10 months. The referral rate for severe SHL was 17.5 cases per 1,000 patient-years. In 53 patients (71%), lactic acidosis (standard bicarbonate [SHCO3]<20 mmol/l) was confirmed, resulting in a referral rate of 12.3 cases per 1,000 patient-years. Twelve patients (16%) died during acute admission (≤30 days). SHCO3<15 mmol/l and pH<7.2 were the only factors associated with acute mortality (odds ratio [OR] 22.5, 95% confidence interval [CI] 2.8–1,045.7 and OR 13.9, 95% CI 2.7–86.9, respectively). A total of 30 less severe cases were rechallenged with zidovudine without recurrence of SHL. Conclusions This study confirms a high incidence of severe SHL in Africa, which has been shown in previous studies. Rechallenge with zidovudine in less severe cases was found to be safe.