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 unkn own. We studied the natural course of the syndrome to develop diagnostic cr iteria and identifying markers that. predict its severity. Methods We assessed 113 patients who were receiving HIV-1 protease inhibito rs (mean 21 months) and 45 HIV-1-infected patients (28 with follow-up) neve r treated with a protease inhibitor. Lipodystrophy was assessed by question naire (including patients' rating of severity), physical examination, and d ual-energy x-ray absorptiometry. Body composition and lasting lipid and gly caemic variables were compared with data obtained 8 months previously. Oral glucose tolerance was investigated. Findings There was 98% concordance between patients' reports of the presenc e or absence of lipodystrophy (reported by 83% of protease-inhibitor recipi ents and 4% of treatment-naive patients; p=0.0001) and physical examination . Patients' ratings of lipodystrophy were significantly associated with dec lining total body fat (p=0.02). Lower body fat was independently associated with longer duration of protease inhibitor therapy and lower bodyweight be fore therapy, and more severe lipodystrophy was associated with higher prev ious (p<0.03) and current (p less than or equal to 0.01) triglyceride and C -peptide concentrations, and less peripheral and greater central fat (p=0.0 05 and 0.09, respectively). Body fat declined a mean 1.2 kg over 8 months i n protease-inhibitor recipients (p=0.05). The prevalence of hyperlipidaemia remained stable over time (74% of treated patients vs 28% of naive patient s; p=0.0001). Impaired glucose tolerance occurred in 16% of protease-inhibi tor 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 t he combination of physical examination, patient's rating, and measurement o f body fat, fasting triglycerides, and C-peptide. Weight before therapy, fa sting triglyceride, and C-peptide concentrations early in therapy, and ther apy duration seem to predict lipodystrophy severity. Lipodystrophy was comm on and progressive after almost 2 years of protease inhibitor therapy, but. was not usually severe. Hyperlipidaemia and impaired glucose tolerance wer e also common.