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- Open Access
Efficient immune reconstitution in HIV+ naïve patients (pts) starting a first lopinavir/ritonavir-containing regimen with low CD4 counts
© Merlini et al; licensee BioMed Central Ltd. 2010
Published: 8 November 2010
Purpose of the study
Investigate immune restoration profile, T-cell activation and microbial translocation in HIV+ naïve pts starting a first LPV/r-containing regimen with low CD4.
40 HIV+ antiretroviral-naive pts starting a first tenofovir/emtricitabine + LPV/r-containing ART with CD4 <350 (20 Late Presenters —LPs, CD4 <100/µL and 20 Non-Late Presenters —NLPs, CD4, 200—350/µL) were followed for 12 months (T12). Microbial translocation (MT) by plasma lipopolysaccharide (LPS) and sCD14 (LAL assay and ELISA), CD38+CD8, CD45R0+38+CD8, CD127+CD4/CD8 (flow cytometry), and plasma IL-7 (ELISA) were tested at T0 and T12. T0 and T12 differences were analyzed by Mann Whitney U test.
Summary of results
At T12, all 40 HIV+ pts displayed a significant CD4 rise, HIV viremia reduction (p=.0006; p<.0001, respectively) and a decrease in activated CD38+CD8 (p<.0001), with a trend to an increase in CD127+CD8 (p=.07). By T12, both LPs and NLPs displayed a significant CD4 increase (LPs: p=.0001; NLPs: p=.001), with LPs maintaining significantly lower CD4 at T12 (p=.0001). At T12, NLPs and LPs displayed a significant reduction in CD38+CD8+ (p=.009; p=.018, respectively); only NLPs displayed a decreasing trend in terminally-differentiated CD45R0+CD38+CD8 (p=.077). Compared to LPs, NLPs featured higher CD127+CD4 proportions at all timepoints (T0, p=.0001; T12, p=.001), with a significant increase in CD127+CD8 by T12 (p=.012), whereas no changes were seen in LPs. NLPs also displayed a significant rise in circulating IL-7 (p=.049), whereas LPs showed a decreasing trend (p=.074). At T0, NLPs showed higher levels of MT markers (LPS: p=.01; sCD14: p=.007). By T12, only NLPs displayed a significant reduction in LPS (p=.022) and in sCD14 (p=.005), whereas no changes were shown in LPs.
In HIV+ antiretroviral-naive pts with low CD4, LPV/r-containing regimens resulted in adequate immune reconstitution and restoration of the IL-7/IL-7R system. Interestingly, microbial translocation was efficiently controlled only in patients with less advanced HIV infection. However, LPV/r-based treatment resulted in a significant reduction of peripheral T-cell activation also in patients with late presentation. Given that T-cell activation is predictive of disease progression, our data advocate the efficacy of LPV/r regimens in broad immune reconstitution in HIV-infected pts with advanced infection.
This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.