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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.

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Open Access This is an open access article distributed under the terms of the Creative Commons Attribution Noncommercial License ( https://creativecommons.org/licenses/by-nc/2.0 ), which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.

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Casana, M., Bellistrì, G., Tincati, C. et al. Abacavir and cardiovascular risk in HIV-infected patients: does T-lymphocyte hyperactivation exert a pathogenic role?. JIAS 11, P88 (2008). https://doi.org/10.1186/1758-2652-11-S1-P88

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  • DOI: https://doi.org/10.1186/1758-2652-11-S1-P88

Keywords

  • Abacavir
  • Memory CD127
  • Central Memory
  • Femoral Vessel
  • Cardiovascular Damage