ArticlesRisk of lipodystrophy in HIV-1-infected patients treated with protease inhibitors: a prospective cohort study
Introduction
After the publication of several case reports, abnormal fat distribution in HIV-1-infected patients receiving antiretroviral therapy was formally described as a clinical entity in 1998, under the name of lipodystrophy syndrome.1 Soon after lipodystrophy was recognised as one of the major limiting factors for long-term antiretroviral therapy. Initially described as a single entity, at least two different syndromes were found to exist: lipoatrophy or loss of subcutaneous fat;2 and central or visceral fat accumulation.3 Despite the difficulties in defining lipodystrophy, a high level of concordance has been seen between the doctor and patient diagnosis of moderate or severe lipodystrophy and the results of dual-energy X-ray absorptiometry (DEXA)4 or sonography.5
Lipodystrophy was initially considered to be only due to HIV-1 protease inhibitors.6 However, lipodystrophy does not invariably develop in all patients treated with protease inhibitors and it has been also described in patients who had never received protease inhibitors. Moreover, reversion of lipodystrophy does not occur after withdrawal of protease inhibitors.7, 8 More recently, several studies have linked the development of lipodystrophy with specific nucleoside reverse transcriptase inhibitors (NRTI).9, 10, 11, 12, 13 Interference with the lipid metabolism and mitochondrial toxicity associated with protease inhibitors6 and NRTI,14 respectively, are postulated to be involved in the pathogenesis of lipodystrophy.
Current studies on risk factors for lipodystrophy have important design limitations.4, 9, 10, 11, 12, 13 Small and sometimes biased population samples have been included, or cross-sectional analysis of mixed retrospective and prospectively followed cohort have been done. In addition, antiretroviral agents have usually been included in the analysis either as the initial prescribed drugs or as the current drugs when the analysis was undertaken.
We report on a prospective cohort study specifically designed to identify risk factors for moderate or severe lipoatrophy and fat accumulation including total exposition to individual antiretroviral agents in a large, unselected sample of antiretroviral-naive patients who were started on highly active antiretroviral therapy (HAART) including two NRTI plus at least one protease inhibitor.
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Patients
All consecutive antiretroviral-naive HIV-1-infected adults who started triple therapy with two NRTIs plus at least one protease inhibitor from October, 1996, to September, 1999, were eligible if they granted oral informed consent to be assessed for clinical lipodystrophy at baseline and in subsequent routine medical visits. Data on body changes were prospectively collected as part of a protocol addressed to analyse the incidence of increased abdominal girth or fat accumulation since the
Study group
During the period of study, 494 antiretroviral-naive adults started HAART containing protease inhibitors. The median CD4-lymphocyte count at baseline was 204 cells per mm3 (IQR 96–342) and median viral load was 4·9 log copies/mL (4·4–5·4). Median known duration of HIV-1 infection was 33 months (3–87), and the median date of starting HAART was December, 1997 (May, 1997, to July, 1998). During a median follow-up of 18 months (10–24), 85 (17%) of the patients developed lipodystrophy. There were
Discussion
The patterns of antiretroviral drugs used were representative of those used in other more-developed countries at that time.16, 17 Previous cross-sectional epidemiological studies have reported a wide variable prevalence ranging from 2% to 84%.6 The incidence of any lipodystrophy in the present study was very similar to the prevalence rates of moderate or severe lipodystrophy in two mixed cross-sectional and longitudinal studies.4, 18
We found a high proportion of patients with overlapping
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