Background:  This 2-year longitudinal study is the first longitudinal study to look at metabolic effects of standard first-line therapy in African patients. Although several studies investigated similar effects in American and European patients, black patients are known to be metabolically different than white patients. In addition, the burden if HIV disease is in Africa, adding to the relevance of the study.

Methods:  We report a 24-month longitudinal observational study conducted at the HIV clinic of the Johannesburg Hospital to investigate the effects of ART on metabolic parameters and body shape changes in black South African HIV⁺ subjects. We enrolled in the study 60 black patients attending the HIV clinic at the Johannesburg, of whom 43 completed it. Anthropometric and metabolic variables were measured every 4 months. These included body mass index, skin-fold thickness, fasting glucose, lipogram, insulin, and C peptide. Lipodystrophy was diagnosed from patient’s own perception and physician observation of body shape changes. Statistical methods employed were multiple regression analysis, and t-tests.

Results:   At the end of 2 years of follow-up, 39% of subjects on stavudine (d4T), lamivudine (3TC), and efavirenz (EFV) had developed lipodystrophy. Prior to initiation of ART these subjects had had higher body mass index (24.7±4.9 vs 22.3±3.2; p <0.05) and skin-fold thicknesses than subjects who did not develop lipodystrophy. After 1 year of therapy none of the subjects had developed lipodystrophy based on their perceptions or physician perception of body shape changes. Body shape changes were apparent after about 18 months of therapy. Subjects with lipodystrophy had significant increases above the baseline value for waist-to-hip ratio (0.79±0.04 to 0.86±0.10; p <0.01), glucose (4.25±0.41 to 4.68±0.62 mM) and triglyceride (1.11±0.77 to 1.45±1.12 mM; p = 0.07) levels whereas subjects without lipodystrophy did not. All subjects, irrespective of the development of lipodystrophy, had significant increases above baseline values for body mass index (23.3±4.2 to 25.1±4.0; p <0.0005) and serum levels of total cholesterol (3.64±0.95 to 4.59±1.18 mM; p <0.0001), cholesterol LDL (2.29±0.73 to 2.67±0.84 mM; p <0.01) and HDL (0.89±0.31 to 1.40±0.49 mM; p <0.0001). These data suggest that subjects who develop lipodystrophy have greater levels of body fat prior to ART than subjects who do not develop lipodystrophy and that in the former subjects ART causes increased waist-to-hip ratio, glucose, and triglyceride concentrations.

Conclusions:  Standard first-line therapy in South Africa leads to increased body mass index and increased serum total, LDL and HDL cholesterol levels independently of any effects on body fat re-distribution. Patients with higher body mass index prior to initiation of ART are at increased risk for developing body fat changes. The risk of developing lipodystrophy increases with longer duration of therapy.