Lipodystrophy body-shape changes in a patient undergoing zidovudine monotherapy (2002)

HIV-related lipodystrophy is a frequent complication in HIV-infected individuals on antiretroviral therapy (ART). Although it has been initially associated with the use of protease inhibitors (PI) [1], patients undergoing therapy with nucleoside analogues only may be equally affected [2]. There is still no consensus definition of HIV lipodystrophy; however, the wasting of peripheral fat combined with central fat accumulation with or without hyperlipidaemia and insulin resistance are the most accepted findings. Its pathogenesis remains obscure, and multiple mechanisms have been involved. Of note is the fact that the effects on adipose tissue seem to differ at different locations [3]. We describe the case of a woman who developed lipodystrophy-related body-shape changes despite being on zidovudine monotherapy for longer than 5 years. Several months after discontinuing zidovudine, she developed ‘buffalo hump’ and supraclavicular lipomatosis. A 42-year-old woman came to our clinic complaining of abdominal and dorsocervical fat enlargement. She had been diagnosed with HIV-1 infection in 1986. Zidovudine was started in 1990 when her CD4 cell count was 550 cells/mm3 (25%). Five years later she complained of progressive thinning in her legs and buttocks. In May 1999, zidovudine was discontinued as the plasma HIV-RNA level was 778 copies/ml and the CD4 cell count was 756 cells/mm3 (28%). Four months later, she presented with progressive abdominal growth and supraclavicular and dorsocervical fat accumulation, which reached a maximal appearance 17 months after the withdrawal of zidovudine (Fig. 1).Fig. 1.: Patient's ‘buffalo hump'.In January 2001, the patient was overweight (body mass index 25.66) and had moderate to severe lipodystrophy, with abdominal and dorsocervical fat pad enlargement, supraclavicular symmetric lipomatosis, and lipoatrophy in her legs and buttocks. The CD4 cell count was 598 cells/mm3and the plasma HIV-RNA level was 1607 copies/ml. Triglyceride, cholesterol and glucose levels were within normal ranges. A significant improvement in both the buffalo hump and peripheral lipoatrophy was observed 26 months after the discontinuation of zidovudine. She is currently not taking ART and her immunological and virological status remains stable. The patient admitted being a smoker but did not drink alcohol. She was engaged in intravenous drug addiction practices until 1990. In 1998, she underwent gynaecological surgery because of cervical intraepithelial neoplasia (grade III). She suffered chronic hepatitis C, and in 1999 she received treatment with interferon plus ribavirin with virological failure. In 2000, her thyroid, adrenal and pituitary functions were analysed because of involuntary weight gain. The hormonal tests were within normal values. She admitted to the sporadic use of citalopram and diazepam because of anxiety, and did not receive other drugs. Treatment with a combination of at least three antiretroviral drugs is currently the standard of care for HIV infection. Therefore, the contribution of each single drug to lipodystrophy is difficult to determine. Fat accumulation has mostly been related to PI [4], whereas nucleoside analogues have been strongly associated with lipoatrophy [2] and only rarely with fat accumulation [1,5–7]. Table 1 records studies in which fat accumulation occurred under PI-sparing combinations [5–7]. Our patient had received zidovudine monotherapy for 9 years, and peripheral lipoatrophy was first manifest after 5 years on therapy. Most of the evidence linking zidovudine and other single nucleoside analogues to lipoatrophy comes from cross-sectional studies. Although stavudine has been associated with lipoatrophy more frequently than other nucleoside analogues [2], recent reports have not confirmed this, noting similar rates of lipodystrophy in individuals exposed to either stavudine or zidovudine-containing regimens [8].Table 1: Fat accumulation in patients receiving protease inhibitor-sparing regimens. The development of fat accumulation several months after discontinuing zidovudine was an unexpected finding. In most instances, the removal of ART is followed by significant improvements in lipid levels without changes in glucose and insulin resistance [9]. Simplification studies have highlighted the fact that insulin resistance improves in non-lipodystrophic HIV-infected patients, whereas it persists in those with lipoatrophy [10,11]. A full reversal of insulin resistance seems to require the normalization of peripheral fat mass [10]. Hypothetically, a release of cytokines as a consequence of discontinuing ART may have resulted in an enhancement of insulin resistance in our patient, because she was suffering from lipoatrophy. In agreement with this, a recent report [12] found a close correlation between insulin resistance, the loss of peripheral fat and elevated serum levels of soluble type 2 TNF-α receptor 2 in HIV-infected patients with lipodystrophy. As is known from type II diabetes, hyperinsulinaemia induces lipogenesis from carbohydrate metabolism, thus promoting the development of increased adipose tissue mass. The patient's peripheral lipoatrophy could have favoured insulin resistance, which was enhanced by increased cytokine production after the cessation of ART. As a consequence, fat accumulation developed. In summary, both lipoatrophy and lipohypertrophy may develop after prolonged exposure to single antiretroviral agents, and the risk may persist even after treatment discontinuation. This observation highlights the complexity of the pathogenic mechanisms involved in the occurrence of body-shape changes with the use of antiretroviral drugs. Teresa García-Benayas Francisco Blanco Jose Manuel Gómez-Viera Ana Barrios Vincent Soriano Juan González-Lahoz