Abacavir and cardiovascular risk in HIV-infected patients: does T-lymphocyte hyperactivation exert a pathogenic role?

Purpose of the study

The association between abacavir exposure and cardiovascular disease (CVD) in HIV-infected patients is currently intensely debated. Recently, the D:A:D Study Group described increased myocardial infarction risk in patients with current/recent abacavir exposure, while repository data from GlaxoSmithKline clinical trials failed to find any association. Given the association between lymphocyte hyperactivation and CVD, and the major role of T-cell hyperactivation in HIV/AIDS, the purpose of our study was to investigate T-cell immunephenotype and proinflammatory cytokines kinetics in HIV-infected patients receiving abacavir-containing regimens.

Methods

Peripheral T-cell immunephenotype and proinflammatory cytokines were evaluated in 11 HIV-infected patients starting on an abacavir-containing HAART at baseline, 3 and 6 months. In particular, the following subpopulations were quantified by flow cytometry: CD38+CD8+, CD95+CD4+ and CD8+, CD127+CD8+. IL-6 and TNF-alpha plasma levels were quantified by ELISA. During abacavir treatment, all the patients underwent ultrasonography of carotid and femoral vessels to evaluate intima-media thickness (IMT).

Summary of results

Major results are shown in Table 1. We observed a significant rise in activated CD38+CD8+ (p < 0.01), and a reduction in CD95+CD4+ and CD8+ (p < 0.01), suggesting CD95 internalization on apoptosis-committed T-cells. A non-significant contraction of central memory CD127+CD8+ was shown, with no changes in plasma IL-6 and TNF-alpha (p > 0.05). Interestingly, during abacavir treatment all patients displayed carotid/femoral thickening involving at least one site.

Table 1

Conclusion

While significantly reconstituting total CD4+, abacavir resulted in significant expansion of activated/senescent/pro-apoptotic T-cell subsets associated to vascular damage. Analogously to other drug-toxicity models, a specific interference of abacavir with purine signaling pathways might be speculated, leading to impairment of lymphocyte activation. By suggesting T-lymphocye hyperactivation as relevant in the pathogenesis of abacavir-related CVD, these data, albeit preliminary, advocate thorough assessment of possible immunologic biomarkers of abacavir-related cardiovascular damage.