Peripheral T-cell apoptosis is not differentially affected by antiretroviral regimens in HIV-infected patients

Background: HIV-induced CD4+ and CD8+ T-cell apoptosis decreases upon start of combination antiretroviral therapy (cART). Although in vitro evidence suggests an antiapoptotic effect of protease inhibitors (PIs) as opposed to non-nucleoside reverse transcriptase inhibitors (NNRTIs), in vivo studies are inconclusive about effects of differential cART regimens on T-cell apoptosis. Methods: Peripheral T-cell apoptosis was evaluated in a cross-sectional study including 20 patients on PIand 19 on NNRTI-based combination antiretroviral therapy (cART), all with backbone therapy of tenofovir and emtricitabine and undetectable viral loads 6 months before inclusion. Spontaneous T-cell apoptosis was measured in freshly isolated peripheral blood mononuclear cells (<4 h after venipuncture) using annexin V, propidium iodide and staining for caspase activity and levels of the anti-apoptotic protein Bcl-2. Results: The groups were comparable in general- and HIVspecific characteristics. In addition, T-cell activation was similar in both groups. We observed no difference in T-cell apoptosis as measured by annexin V, propidium iodide or caspase staining between PI- and NNRTI-treated patients. Interestingly, the level of anti-apoptotic protein Bcl-2 was higher in PI-treated than in NNRTI-treated patients. Conclusions: In this cross-sectional study on HIVinfected patients, direct ex vivo spontaneous T-cell apoptosis rates are not differentially affected by NNRTI- or PI-based cART.