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Lipodystrophy in HIV-1-infected patients

1999; Elsevier BV; Volume: 354; Issue: 9181 Linguagem: Inglês

10.1016/s0140-6736(05)75937-7

1474-547X

P. Mercié, S. Tchamgoué, François Dabis, Jean‐Luc Pellegrin,

HIV/AIDS drug development and treatment

Andrew Carr and colleagues (June 19, p 2093)1Carr A Samaras K Thorisdottir A Kaufmann GR Chisholm DJ Cooper DA Diagnosis, prediction, and natural course of HIV-1 protease-inhibitor-associated lipodystrophy, hyperlipidaemia, and diabetes mellitus: a cohort study.Lancet. 1999; 353: 2093-2099Summary Full Text Full Text PDF PubMed Scopus (1428) Google Scholar report the results of a longitudinal study of 113 HIV-1- infected patients who were receiving protease inhibitors and were followed up for 21 months (92 cases of lipodystrophy) and 45 treatment-naïve patients who were followed up for 28 months (one case of lipodystrophy). They propose a classification of lipodystrophy associating the clinical anomalies with metabolic disorders that would make the results of different studies sufficiently homogeneous for comparisons to be made. Comparison between patients with and without lipodystrophy showed that the former had taken protease inhibitors and had been HIV-1-seropositive for longer, but that their CD4-cell counts and virus loads were similar. Development of lipodystrophy did not seem to be associated with the particular protease inhibitor used, but onset was more rapid with ritonavir or saquinavir. Some of our findings corroborate those of Carr and colleagues. We used the same clinical (with patients self-reporting) and biological selection criteria, and diagnosed 61 (26·2%) lipodystrophy cases among our 233 HIV-1-infected patients: two (3%) had not been treated, five (8%) had received a two-drug regimen, and 54 (89%) were taking at least three drugs, one of which was a protease inhibitor. Compared with patients without lipodystrophy, patients with lipodystrophy were older (38·8 [SD 9] vs 44·8 [10·2] years, p < 0·0001), had lower mean CD4-cell counts (503 [270] vs 395 [259]/μL; p=0·007), and a greater proportion had progressed to AIDS (17·1 vs 38·3%, p=0·0007; odds ratio 3·2 [95% CI 1·47–6·2]); the mean body-mass index differed only slightly (2·8 [3·10] vs 21·9 [2·54] kg/m2, p=0·03), and virus loads were similar (72·7 vs 67·2% with <500 copies/mL). Among 216 (92·7%) patients on therapy, 140 (64·8%) were receiving a protease inhibitor. Among the 59 patients with lipodystrophy who were being treated, 46 (78%) were receiving a protease inhibitor. At the time of lipodystrophy diagnosis, lamivudine was being taken by 160 (74%) and stavudine by 147 (68%) treated patients, compared with 45 (76%) and 46 (78%), respectively, of those with lipodystrophy. We calculated the theoretical duration of exposure to antiretroviral drugs of all our patients since the first day of treatment and found no difference between patients with and without lipodystrophy (table). We believe that the significant association with lamivudine and stavudine (p < 0·05) may be biased because of the large number of patients treated with these drugs who had previously received other nucleoside analogues. However, all patients with lipodystrophy had been treated longer than patients without this disorder.TableDuration of exposure to antiretroviral drugsWithout lipodystrophyWith lipodystrophyp*For difference in duration.PatientsMean (SD) duration (months)PatientsMean (SD) duration (months)Nucleoside analoguesZidovudine10623·9 (20·0)4529·7 (22·1)0·11Didanosine7213·9 (11·9)2615·5 (15·9)0·60Zalcitabine6720·0 (12·2)3916·2 (8·9)0·08Lamivudine10715·3 (6·3)4717·9 (6·7)0·02Stavudine9815·4 (8·2)4918·2 (7·7)0·04Protease inhibitorsSaquinavir5212·9 (7·4)3113·5 (7·3)0·72Ritonavir199·5 (8·9)1312·6 (6·1)0·29Indinavir5112·3 (9·0)3913·7 (8·6)0·52Nelfinavir494·2 (3·0)275·0 (2·9)0·26* For difference in duration. Open table in a new tab At present, no drugs can be associated more than another with the development of lipodystrophy. Intensification of therapy with a protease inhibitor increases the risk of lipodystrophy as a function of age, CD4-cell count, and disease stage (ie, patients treated for longer with multiple antiviral agents).