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Introduction: Lipodystrophy is still a matter of concern in HIV+ patients receiving ART. However, long-term fat change in patients taking non-thymidine regimens is not well known., Materials and Methods: A prospective ongoing fat change assessment including clinical evaluation and dexa scans (Hologic QDR 4500) is being conducted in all consecutive patients initiating ART from January 2008. Arm, leg, trunk and total fat as well as fat mass ratio (FMR=% trunk fat/% leg fat) were determined. Patients with data at baseline (BL), 12 and 36 m are included in this analysis. ITT and OT were performed. Multivariate general linear models were used to assess changes in fat measures., Results: One hundred patients were included. 81% men, 42.9 years, 18% AIDS, CD4 218.5 (6-756), viral load 5 log (2.9-6.8), leg fat 4644g, trunk fat 6693g, FMR 0.94. Around 40 patients (40%) initiated a PIr (17 LPVr, 11 ATVr, 9 DRVr, 3 FPVr), 34 (34%) NVP and 21 (21%) EFV. About 83% received TDF/FTC and 10% ABC/3TC. Groups were comparable at BL except for a lower viral load in NVP patients (p=0.047) and lower c-LDL in PI patients (p=0.043). After 36 m, no patient presented a clinically evident lipodystrophy. At 12 m, an overall significant increase was found from baseline in trunk, leg and FMR (median 759 g, 479.4 g and 0.03, respectively, p<0.05) and at 36 m in trunk and leg fat (median 989.9 g, 566 g, respectively, p<0.05). According to ART, at 12 m a significant increase in trunk and leg fat was observed in EFV and PIr. At 36 m, in NVP patients trunk and leg fat as well as FMR increased, whereas in PIr patients only leg fat increased (see figure). In ITT analysis, adjusted by age, sex, risk practice and BL CD4, EFV was associated with a greater increase in FMR (p=0.036) at 36 m vs PIr. In OT analysis, at 12 m, NVP was associated with a smaller percentage increase in trunk fat (vs PIr and EFV, p=0.006) and in leg fat (vs PIr, p=0.046). These differences did not persist at 36 m., Conclusions: In this cohort of patients taking non-thymidine-based regimens, after 36 m without a clinically evident lipodystrophy, no significant changes in FMR were observed. However, some differences in fat redistribution according to ART were present: PIr was associated with an initial and continuous increase in trunk and leg fat, NVP with a slower and progressive increase in both fat compartments, while in EFV patients, the initial fat increase was followed by a decrease in peripheral fat at 36 m. Longer follow up will help to confirm these trends.

Introduction: Previous studies have described improvements on lipid parameters when switching from other antiretroviral drugs to tenofovir (TDF) and impairments in lipid profile when discontinuing TDF. [1-3] It is unknown, however, if TDF has an intrinsic lipid-lowering effect or such findings are due to the addition or removal of other offending agents or other reasons., Materials and Methods: This was a randomized, crossover, double-blind, placebo-controlled clinical trial (NCT 01458977). Subjects with HIV-1 RNA <50 copies/mL during at least 6 months on stable DRV/r (800/100 mg QD) or LPV/r (400/100 mg BID) monotherapy, with confirmed fasting total cholesterol ≥200 or LDL-cholesterol ≥130 mg/dL and not taking lipid-lowering drugs were randomized to (A) adding TDF/FTCduring 12 weeks followed by 24 weeks without TDF/FTC, or (B) continuing without TDF/FTC for 12 weeks, adding TDF/FTC for 12 weeks and then withdrawing TDF/FTC for 12 additional weeks. Randomization was stratified by DRV/r or LPV/r use at study entry. All subjects received a specific dietary counselling. Primary endpoints were changes in median fasting total, LDL and HDL-cholesterol 12 weeks after TDF/FTC addition. Analyses were performed by ITT., Results: 46 subjects with a median age of 43 (40-48) years were enrolled in the study: 70% were male, 56% received DRV/r and 44% LPV/r. One subject withdrew the study voluntarily at week 4 and another one interrupted due to diarrhoea at week 24. Treatment with TDF/FTC decreased total, LDL and HDL-cholesterol from 235.9 to 204.9 (p<0.001), 154.7 to 127.6 (p<0.001) and 50.3 to 44.5 mg/dL (p<0.001), respectively. In comparison, total, LDL and HDL-cholesterol levels remained stable during placebo exposure. Week 12 total cholesterol (p<0.001), LDL-cholesterol (p<0.001) and HDL-cholesterol (p=0.011) levels were significantly lower in TDF/FTC versus placebo. Treatment with TDF/FTC reduced the fraction of subjects with abnormal fasting total-cholesterol (≥200 mg/dL) from 86.7% to 56.8% (p=0.001) and LDL-cholesterol (≥130 mg/dL) from 87.8% to 43.9% (p<0.001), which was not observed with placebo. There were no virological failures, and CD4 and triglyceride levels remained stable regardless of exposure., Conclusion: Coformulated TDF/FTC has an intrinsic lipid-lowering effect, likely attributable to TDF.

Introduction: Plasma trough concentrations of lopinavir (LPV) given as LPV/r 800/200 mg once daily (OD) are reduced in comparison with 400/100 mg twice daily (BID). While OD dosage of LPV/r is sufficient to achieve viral suppression in plasma, data about drug penetration and viral suppression in central nervous system (CNS) is needed, mainly if LPVr is used as maintenance monotherapy strategy in selected patients. The objective of this study was to evaluate CSF HIV-1 RNA and CSF LPV concentrations in patients receiving LPV/r monotherapy OD (LPVrMOD)., Material and Methods: This is a cross-sectional sub-study within a prospective, open-label pilot simplification study to evaluate the efficacy and safety of LPV/rMOD in virologically suppressed patients previously receiving a BID LPV/r monotherapy regimen (LPV/rMBID), the "Kmon study" (NCT01581853). To assess LPV concentrations and HIV-1 RNA in CSF, a lumbar puncture (LP) was performed in a subgroup of patients after at least one month of LPVrMOD treatment. Plasma-paired samples of all patients were also obtained. HIV-1 RNA was determined by real-time PCR (limit of detection 40 copies/mL). Liquid chromatography-tandem mass spectrometry (Tandem labs, NJ) was used to determine CSF and blood plasma LPV concentrations., Results: Nine patients were included. Median (range) age was 48 (34-56) years, median CD4 cell count 672 (252-1,408) cells/mL, median nadir CD4 count 125 (35-537) cells/mL and 40% of subjects were HCV-positive. Before starting LPV/rMOD median time on a LPV/r-containing regimen and on LPV/rMBID were 9 (4-11) years and 15 (7-24) months respectively, median time with undetectable HIV viral load was 5 (3-12) years and 2 patients had a previous documented blip. LP was performed a median of 24 (8-36) weeks after starting LPV/rMOD and 24 (11-28) hours after the last LPV/rMOD dose CSF and plasma HIV RNA was 40 copies/mL in all patients. Median LPV CSF concentration was 9.78 (1.93-78.3) ng/mL, median LPV plasma concentration 1,103 (377-16,700) ng/mL and median LPV CSF/plasma ratio 0.3% (0.1-1.2)., Conclusions: No CSF viral escape was detected and LPV concentrations were above the IC50 for wtHIV-1 (1.9 ng/mL). However, as concentrations were close to IC50 in some patients, a careful clinical follow up of patients receiving this regimen would be advisable. Larger longitudinal studies will be helpful for a better understanding of the CNS antiviral activity of LPVr monotherapy.