Background:  Due to the emergence of HIV-1 associated lipodystrophy, multiple investigators have attempted to hypothesize the causes of this syndrome.  Host, disease, and treatment factors have been shown to be associated with lipodystrophy.  Lipoatrophy and lipoaccumulation may have different pathogenic mechanisms.  The purpose of this study was to evaluate those factors specifically associated with the development of lipoatrophy.

Methods:  A prospective cohort analysis of 337 HIV-1-infected patients without any signs of lipoatrophy at the initation of the study was conducted to identify the factors associated with the development of lipoatrophy 21 months later.  Standardized interview and physician assessment of clinical signs at each survey were performed.  The incidence of moderate or severe fat loss of extremities, hips or buttocks and sunken cheeks—i.e., without total body weight loss, as distinct from HIV wasting--was analyzed in stratified and multivariate analyses for their relationship to immunologic, virologic, clinical and drug treatment data for each patient.

Results:  The proportion of patients who developed moderate or severe lipoatrophy was 13.1% (44/337) between the 2 surveys.  In multivariate analyses significant risk factors were white race (OR, 5.17; 95% CI 1.93-17.13), CD4+ T-lymphocyte count at Survey 2 less than vs. more than 100 cells/mm³ (OR, 4.15; 95% CI 1.34-13.07), and body mass index less than vs. greater than 24 kg/m² (OR, 2.43; 95% CI 1.14-5.35).  There was no association with duration of use, initiation, continuation, or discontinuation of any antiretroviral medication with the development of lipoatrophy.  When the comparisons were controlled for the severity of HIV illness, there appeared to be little, if any, effect of any antiretroviral agent or class of agents on the development of lipoatrophy.

Conclusions:  Factors associated with severity of HIV-1 infection, especially CD4+ T-lymphocyte cell count, appeared to have the strongest association with the development of lipoatrophy.