Abacavir treatment and biomarkers associated with cardiovascular disease (CVD) in HIV-1-infected patients on effective antiretroviral therapy
Background. An increased risk of myocardial infarction was observed in patients with current/recent exposure to abacavir. We analysed the effect of different treatment patterns on CVD-associated biomarkers in longitudinal samples from ICONA enrollees.
Methods. We selected patients on cART who, in the period between pairs of longitudinally stored plasma samples, had a VL< 400 copies/mL and were: starting abacavir (group A), continuing abacavir (group B), stopping abacavir (group C) not receiving abacavir (group D). hsCRP, IL-6, D-dimer, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) levels were quantified . Changes within groups and differences in changes between groups were analysed using non-parametric tests and by linear regression models adjusting for prior AIDS, CD4, VL, concomitant drugs use, age, gender, smoking status and lipids.
Results. Pairs of tests from 62 patients were examined (group A n=26, B=22, C=7, D=7): 67%M; at first sample median age was 38y, VL had previously been < 400 for 3.3y. Patients on abacavir showed higher levels of PAI-1 (n=80, median=190ng/mL) as compared to those currently not (n=48, 104ng/mL, p=0.0001). No significant difference was detected comparing changes of the different molecules over paired longitudinal samples within and between groups (median sample distance 0.73y) (table).
| Group A Mean Δlog (p-value) | Group B Mean Δlog (p-value) | Group C Mean Δlog (p-value) | Group D Mean Δlog (p-value) | p-value (Kruskal Wallis) for difference between groups | |
| t-PA | -13% (0.027) | -1% (0.882) | +9% (0.691) | +11% (0.623) | 0.346 |
| PAI-1 | +3% (0.676) | +1% (0.648) | +5% (0.561) | -6% (0.678) | 0.398 |
| D-dimer | -7% (0.042) | -3% (0.274) | -2% (0.716) | +22% (0.313) | 0.447 |
| hsCRP | -28% (0.528) | +173% (0.467) | -284% (0.295) | +12% (0.871) | 0.624 |
| IL-6 | -88% (0.040) | -46% (0.471) | -137% (0.155) | -10% (0.356) | 0.904 |
Similar results were obtained when analysing annual changes and in multivariate analyses.
Conclusion. In patients with suppressed viral load on ART, abacavir treatment was associated with higher levels of a biomarker indicating a reduced fibrinolytic capacity but no significant changes in biomarkers were observed over longitudinal measures.
A. De Luca1, K. De Gaetano Donati1, A. Cozzi-Lepri2, A. De Curtis3, M.R. Capobianchi4, A. Antinori5, G. Scalise6, G. Magnani7, V. Vullo8, R. Cauda1, L. Iacoviello3, A. d'Arminio Monforte9, ICONA Foundation Study Group
1Catholic University, Institute of Clinical Infectious Diseases, Rome, Italy, 2Royal Free and University College Medical School, London, United Kingdom, 3Catholic University, Laboratory of Genetic and Environmental Epidemiology, Campobasso, Italy, 4IRCCS Ospedale Lazzaro Spallanzani, Department of Virology, Rome, Italy, 5IRCCS Ospedale Lazzaro Spallanzani, Clinical Department, Rome, Italy, 6Università Politecnica delle Marche, Clinic of Infectious Diseases, Ancona, Italy, 7Hospital of Reggio Emilia, Clinic of Infectious Diseases, Reggio Emilia, Italy, 8University 'La Sapienza', Department of Clinical Infectious Diseases, Rome, Italy, 9University of Milan, Institute of Infectious and Tropical Medicine, Milan, Italy