Diagnosis, prediction, and natural course of HIV-1 protease-inhibitor-associated lipodystrophy, hyperlipidaemia, and diabetes mellitus: a cohort study
BACKGROUND: The prevalence and severity of lipodystrophy syndrome with long-term therapy for HIV-1 infection that includes a protease inhibitor is unknown. We studied the natural course of the syndrome to develop diagnostic criteria and identifying markers that predict its severity. METHODS: We assessed 113 patients who were receiving HIV-1 protease inhibitors (mean 21 months) and 45 HIV-1-infected patients (28 with follow-up) never treated with a protease inhibitor. Lipodystrophy was assessed by questionnaire (including patients' rating of severity), physical examination, and dual-energy x-ray absorptiometry. Body composition and fasting lipid and glycaemic variables were compared with data obtained 8 months previously. Oral glucose tolerance was investigated. FINDINGS: There was 98% concordance between patients' reports of the presence or absence of lipodystrophy (reported by 83% of protease-inhibitor recipients and 4% of treatment-naive patients; p=0.0001) and physical examination. Patients' ratings of lipodystrophy were significantly associated with declining total body fat (p=0.02). Lower body fat was independently associated with longer duration of protease-inhibitor therapy and lower bodyweight before therapy, and more severe lipodystrophy was associated with higher previous (p < 0.03) and current (p < or = 0.01) triglyceride and C-peptide concentrations, and less peripheral and greater central fat (p=0.005 and 0.09, respectively). Body fat declined a mean 1.2 kg over 8 months in protease-inhibitor recipients (p=0.05). The prevalence of hyperlipidaemia remained stable over time (74% of treated patients vs 28% of naive patients; p=0.0001). Impaired glucose tolerance occurred in 16% of protease-inhibitor recipients and diabetes mellitus in 7%; in all but three patients these abnormalities were detected on 2 h post-glucose load values. INTERPRETATION: Diagnosis and rating severity of lipodystrophy is aided by the combination of physical examination, patient's rating, and measurement of body fat, fasting triglycerides, and C-peptide. Weight before therapy, fasting triglyceride, and C-peptide concentrations early in therapy, and therapy duration seem to predict lipodystrophy severity. Lipodystrophy was common and progressive after almost 2 years of protease inhibitor therapy, but was not usually severe. Hyperlipidaemia and impaired glucose tolerance were also common.
|Authors||Carr, A.;Samaras, K.;Thorisdottir, A.;Kaufmann, G. R.;Chisholm, D. J.;Cooper, D. A. :|
|Responsible Garvan Author|
|URL link to publisher's version||http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10382692|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/1258|