The effects of intermittent, CD4-guided antiretroviral therapy on body composition and metabolic parameters

Objective: To assess the effects of decreased antiretroviral therapy exposure on body fat and metabolic parameters. Design: Substudy of the Strategies for Management of Anti-Retroviral Therapy study, in which participants were randomized to intermittent CD4-guided [Drug Conservation (DC) group] or to continuous [Viral Suppression (VS) group] antiretroviral therapy. Methods: Participants at 33 sites were coenrolled in the Strategies for Management of Anti-Retroviral Therapy Body Composition substudy. Regional fat was assessed annually by whole-body dual-energy X-ray absorptiometry and abdominal Computed tomography. Fasting metabolic parameters were assessed at months 4, 8, and annually. Treatment groups were compared for changes in fat and metabolic markers using longitudinal mixed models. Results: Two hundred and seventy-five patients were randomized to the DC (n = 142) or VS (n = 133) group and followed for a median of 2.0 years. By month 12, limb fat (DC-VS difference 9.8%, 95% confidence interval 3.5-16.1; P=0.003) and subcutaneous abdominal fat (DC-VS difference 14.3 cm(2), 95% confidence interval -0.1 to 28.7; P=0.05) increased in the DC group. There was no treatment difference in visceral abdominal fat (DC-VS difference -2.1%, 95% confidence interval -13.5 to 9.4; P=0.72). Lipids significantly decreased in the DC group by month 4 and treatment differences persisted throughout follow-up (P <= 0.001). By 12 months, hemoglobin A1C increased in the DC (+0.3%) and remained stable in the VS group (P=0.003); the treatment difference remained significant throughout follow-up (P=0.02). Conclusion: After 12 months, intermittent antiretroviral therapy increased subcutaneous fat, had no effect on visceral abdominal fat, decreased plasma lipids, and increased hemoglobin A1C compared with continuous antiretroviral therapy. (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkin

Continuous antiretroviral therapy decreases bone mineral density

Objectives: To assess the effects of anti retroviral therapy (ART) on bone mineral density (BMD) Design: Randomized comparison of continuous ART (viral suppression group; VS) with intermittent ART (drug conservation group; DC) Setting: Outpatient clinics in the United States, Australia, and Spain. Participants: Participants in the Strategies for Management of Antiretroviral Therapy (SMART) Body Composition substudy. Main outcome measures: Annual hip and spine BMD by dual-energy radiographic absorptiometry (DXA) and spine BMD by quantitative computed tomography (qCT). Methods: Comparisons were by intention-to-treat analysis, using longitudinal models for change in BMD. Risk factors for BMD loss were evaluated. Results: The 214 participants (median 44 years, 19% female participants, 73% on ART; median T-scores -0.5 total hip, -0.7 spine DXA, -0.9 spine qCT; 98 randomized to VS and 116 to DC) were followed for a mean 2.4 years. With continuous ART, BMD declined per year by 0.8% (hip), 0.41% (spine DXA), and 2.41% (spine qCT). BMD declined significantly less with intermittent ART. Estimated DC minus VS group differences in mean BMD change through follow-up were 1.4% [hip; 95% confidence interval (CI) 0.6-2.3; P=0.0021, 1.3% (spine DXA; 95% Cl 0.1-2.4, P=0.03), and 3.0% (spine qCT; 959% Cl 0.8-5.2, P=0.007). No consistent drug-specific association with BMD decline was found. In the parent study, 10 of 2753 participants in the VS group and two of 2720 in the DC group reported serious fractures (hazard ratio 4.9; 95% Cl 1.1-22.5; P=0.04). Conclusion: Continuous ART is associated with decline in BMD and possibly more fractures relative to intermittent, CD4 cell count-guided ART. (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkin