Previous reports confirm this finding in that RAL has only mild affects (increase of 2 mg/dL) on glucose metabolism over 96 weeks [14]. limb fat changes at 48 weeks with baseline variables were assessed by backward stepwise multivariate linear regression. Analyses were adjusted for gender, body mass index and smoking status. Results 210 participants were randomised. The mean (95% CI) increase in limb fat over 48 weeks was 15.7% (5.3, 25.9) or 0.9 kg (0.2, 1.5) in the r/LPV+N(t)RTI arm and 21.1% (11.1, 31,1) or 1.3 kg (0.7, 1.9) in the r/LPV+RAL arm, with no significant difference between treatment arms (?5.4% [?0.4 kg], p 0.1). Increases in Sarsasapogenin total body fat mass (kg) and trunk fat mass (kg) were also similar between groups. Total:HDL Sarsasapogenin cholesterol ratio was significantly higher in the RAL arm (mean difference ?0.4 (1.4); p?=?0.03), there were no other differences in lipid parameters between treatment arms. There were no statistically significant differences in CVD risk or incidence of Metabolic Syndrome between the two treatment arms. The baseline predictors of increased limb fat were high viral load, high insulin and participant’s not taking lipid lowering treatment. Conclusion In patients switching to second line therapy, r/LPV combined with RAL demonstrated similar improvements in limb fat as an N(t)RTI + r/LPV regimen, but a worse total:HDL cholesterol ratio over 48 weeks. Trial Registration This clinical trial is registered on Clinicaltrials.gov, registry number “type”:”clinical-trial”,”attrs”:”text”:”NCT00931463″,”term_id”:”NCT00931463″NCT00931463. Introduction HIV associated lipodystrophy is a syndrome of peripheral lipoatrophy, central fat accumulation, and lipid derangement. Lipodystrophy complicates the management of HIV-infected patients through dyslipidaemia, increased cardiovascular disease (CVD) risk and cosmetic affect. Both HIV infection itself and long term exposure to combination antiretroviral therapy (cART) have been implicated in the pathogenesis of lipodystrophy, which can affect up to 50% of individuals receiving cART [1]C[4]. The use of thymidine analogue nucleotide reverse transcriptase inhibitors (ta-NRTIs) has been minimised in high-income countries, as they have been implicated as the main CITED2 cause of lipoatrophy and other severe adverse events [1]C[8]. However, ta-NRTIs are still commonly used as first-line treatment in low and middle-income countries because of their comparatively low cost. Changes in circulating lipoproteins have been demonstrated with use of three of the major antiretroviral drug classes (protease inhibitors [PI], nucleoside/nucleotide reverse transcriptase inhibitors [N(t)RTI] and non-nucleoside reverse transcriptase inhibitors [NNRTI]), although the pattern of changes differ between and among the three drug classes [5], [9]C[13]. Recent clinical trials using the integrase inhibitor, raltegravir (RAL), in antiretroviral na?ve [14], [15] and cART experienced participants [16], [17] have reported various effects on lipids. Results vary from reports of small increases [14] to significant increases [15], [16], whereas others report improvements [17] in the lipid profile, compared Sarsasapogenin to N(t)RTIs, PIs or efavirenz. An study has demonstrated RAL had minimal affects on the expression of peroxisome proliferator activated receptor (PPAR-) and sterol regulatory element Sarsasapogenin binding protein (SREBP-1c), which are involved in lipid accumulation [18]. Adipose tissue changes associated with RAL have also been assessed in three small studies, which demonstrated no significant change in body fat with RAL over 48 weeks compared Sarsasapogenin to N(t)RTI/PI based regimens [16], [19] or comparable increases in body fat to efavirenz [14]. More recently the larger PROGRESS study 96 week results demonstrated lopinavir/ritonavir (r/LPV) plus RAL increased peripheral fat, but not trunk fat compared to r/LPV plus tenofovir/emtricitabine [20]. The Metabolic Syndrome is a condition characterised by the clustering of alterations in glucose metabolism, lipid metabolism, fat accumulation and blood pressure. Several studies have reported a high prevalence of the Metabolic Syndrome in HIV populations [21]C[24], which may be due to cART.