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No evidence for recent abacavir/lamivudine use in promoting inflammation, endothelial dysfunction, hypercoagulability, or insulin resistance in virologically suppressed HIV-infected patients: a substudy of the BICOMBO randomized clinical trial (ISRCTN6189
Presented by Esteban Martinez (Spain).
E. Martinez1, M. Larrousse1, I. Perez1, M. Loncá1, D. Podzamczer2, F. Gutierrez3, R. Deulofeu1, R. Casamitjana1, J.C. Reverter1, J. Mallolas1, J. Pich1, J.M. Gatell1, for the BICOMBO Study Group
1Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain, 2Hospital de Bellvitge, L'Hospitalet de Llobregat, Spain, 3Hospital General Universitario de Elche, Elche, Spain
Background: Inflammation, plaque instability, and/or thrombosis are suggested mechanisms for cardiovascular disease associated with recent abacavir use in some cohort studies. To avoid bias due to HIV replication and drug prescription, we assessed 48-week changes in markers of inflammation, endothelial dysfunction, hypercoagulability, and insulin resistance in otherwise healthy, virologically suppressed HIV-infected patients randomly switched to abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC).
Methods: Patients with no history of cardiovascular disease, no prior ABC or TDF use, and no virological failure during follow-up were included. Fasting serum high-sensitive C reactive protein (CRP), monocyte chemoattractant protein-1 (MCP-1), osteoprotegerin (OPG), adiponectin, IL-6, IL-10, TNF-a, ICAM-1, VCAM-1, selectin E and P, D-dimer, and insulin were measured. Mann-Whitney and Spearman tests were used for comparisons and correlations, respectively.
Results: Eighty (46 ABC/3TC, 34 TDF/FTC) patients included. At baseline, gender (80% males), age (median 43 years), antiretroviral exposure (median 3.6 years), and Framingham score (median 4.4) were similar between groups and between patients in the substudy vs those not. There were no significant differences in baseline markers between groups. As expected, ICAM-1 and VCAM-1 (r=0.51, P< 0.0001), and selectin E and P (r=0.63, P< 0.0001) were correlated at baseline. At baseline, OPG, selectin E and P were also correlated with Framingham score. Median 48-week percent changes in markers between ABC/3TC and TDF/FTC groups were: CRP (-3.9 vs 0.0), MCP-1 (5.9 vs 4.0), OPG (5.1 vs -2.8), adiponectin (-2.2 vs 15.4), ICAM-1 (6.6 vs 5.2), VCAM-1 (8.4 vs -2.0), selectin E (-0.4 vs 7.8), selectin P (4.6 vs 12.6), D-dimer (0.0 vs 0.0), and insulin (-2.5 vs 8.8) (P≥0.12 for all comparisons). IL-6, IL-10, and TNF-a at baseline and 48 weeks were undetectable for most patients.
Conclusions: These results do not support a role of recent ABC/3TC use in promoting inflammation, endothelial dysfunction, hypercoagulability, or insulin resistance in virologically suppressed HIV-infected patients.
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