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Efficient immune reconstitution in HIV+ naïve patients (pts) starting a first lopinavir/ritonavir-containing regimen with low CD4 counts
Journal of the International AIDS Society volume 13, Article number: P17 (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.
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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.
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Merlini, E., Sinigaglia, E., Carpani, G. et al. Efficient immune reconstitution in HIV+ naïve patients (pts) starting a first lopinavir/ritonavir-containing regimen with low CD4 counts. JIAS 13 (Suppl 4), P17 (2010). https://doi.org/10.1186/1758-2652-13-S4-P17
- Immune Reconstitution
- Microbial Translocation
- Immune Restoration
- Advanced Infection
- Plasma Lipopolysaccharide