Monitoring the toxicity of antiretroviral therapy in resource limited settings: a prospective clinical trial cohort in Thailand.

BACKGROUND One of the many challenges which come together with the implementation of antiretroviral therapy (ART) in settings with limited resources is the monitoring of toxicity. This monitoring increases costs of ART and strains resources. We therefore investigated the necessity for laboratory toxicity monitoring of ART in Thailand. DESIGN, METHODS AND PARTICIPANTS: A prospective Thai cohort of 417 HIV-infected patients were enrolled in randomized clinical trials investigating ART. Time-dependent occurrence of grade III/IV abnormal laboratory values as defined by the AIDS Clinical Trial Group was analysed. RESULTS During a median observation period of 3.7 years (2.4-4.3) 142 grade III/IV toxicities occurred in 101 (24.2%) patients. Hepatic toxicity (n = 33, 7.9%), hypercholesterolaemia (n = 57, 13.7%), hypertriglyceridaemia (n = 26, 6.2%), anaemia (n = 16, 3.8%) and low platelet counts (n = 8, 1.9%) were frequently observed. Anaemia and low platelets occurred early and during the first 2 years of ART. Hepatic toxicity was seen early and throughout the observation period. Hypertriglyceridaemia and hypercholesterolaemia occurred throughout the observation period, and increased over time. Hypercreatininaemia and hyperglycaemia occurred once after 120 and 132 weeks. ART was changed or interrupted for grade III/IV hepatic toxicity, anaemia and hyperglycaemia only. The incidence rate for grade III/IV toxicity was between 5.56 (95% CI, 6.76-18.02) for low platelet counts and 41.18 (31.77-53.39) per 1000 patient years for hypercholesterolaemia. Antiretrovirals used were zidovudine, stavudine, lamivudine, zalcitabine, didanosine, efavirenz, saquinavir, ritonavir and indinavir. CONCLUSIONS Grade III/IV toxicity is frequently observed in Thai patients treated with ART. The simple and inexpensive monitoring of ALT and haemoglobin could prevent most serious short-term toxicity. Long-term toxicity can be addressed with a yearly monitoring of triglycerides, cholesterol, glucose and creatinine if nephrotoxic drugs are used.