A syndrome of lipoatrophy, lactic acidaemia and liver dysfunction associated with HIV nucleoside analogue therapy: contribution to protease inhibitor-related lipodystrophy syndrome

Background: Lipodystrophy (LD; peripheral lipoatrophy, central adiposity) h yperlipidaemia and insulin resistance often complicate protease inhibitor-c ontaining antiretroviral therapy. Lipoatrophy and abdominal distension were observed in protease inhibitor-naive nucleoside analogue reverse transcrip tase inhibitor (NRTI) recipients with lactic acidaemia and hepatic impairme nt, which are known NRTI-induced mitochondrial toxicities. Design and setting: Case-control study in a university-based outpatient cli nic. Patients and methods: The patients studied included 14 NRTI recipients with lipoatrophy, 32 antiretroviral-naive patients without LD, 28 NRTI recipien ts without LD, 44 combined NRTI-protease inhibitor recipients without LD, a nd 102 NRTI-protease inhibitor recipients with LD. Data was obtained on bod y composition (questionnaire, physical examination, dual-energy x-ray absor ptiometry and abdominal computerized tomography), with biochemical, lipid a nd glycaemic parameters. Results: The NRTI-LD syndrome was characterized by recent onset fatigue and nausea, peripheral lipoatrophy (6 kg loss over 4 months), abdominal disten sion (ascites +/- hepatomegaly) and elevated lactate (4.6, 7.1, 1.2, 1.4 an d 1.7 mmol/l, respectively; P < 0.0001) and liver enzymes. Cases without he patic involvement also had lower body fat and greater lactate than unaffect ed controls. Metabolic disturbances and weight improved after cessation. Th e NRTI-LD syndrome differed from protease inhibitor-related LD syndrome by the presence of recent onset symptoms and weight loss, higher lactate and a lanine aminotransferase, and lower albumin, cholesterol, triglycerides, glu cose and insulin. In treated controls, current stavudine therapy, protease inhibitor duration, and lactic acidaemia were independently associated with both lipoatrophy and abdominal obesity; total NRTI duration was also assoc iated with lipoatrophy, and lamivudine and protease inhibitor duration with buffalo hump. Conclusions: A syndrome of lipoatrophy, constitutional illness, lactic acid aemia and hepatic dysfunction can complicate NRTI therapy. Both protease in hibitor and NRTI therapies, particularly if associated with lactic acidaemi a, contribute to LD syndrome, but have some distinguishable clinical and me tabolic effects. (C) 2000 Lippincott Williams & Wilkins.