Effect of raltegravir-containing intensification on HIV burden and T-cell activation in multiple gut sites of HIV-positive adults on suppressive antiretroviral therapy

含雷替拉韦强化治疗对接受抑制性抗逆转录病毒治疗的 HIV 阳性成人患者肠道多个部位 HIV 负担和 T 细胞活化的影响

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作者:Steven A Yukl, Amandeep K Shergill, Kenneth McQuaid, Sara Gianella, Harry Lampiris, C Bradley Hare, Mark Pandori, Elizabeth Sinclair, Huldrych F Günthard, Marek Fischer, Joseph K Wong, Diane V Havlir

Conclusion

Most HIV RNA and DNA in the blood and gut is not the result of ongoing replication that can be impacted by short-term intensification with raltegravir. However, the ileum may support ongoing productive infection in some patients on ART, even if the contribution to plasma RNA is not discernible.

Methods

Seven HIV-positive adults received 12 weeks of ART intensification with raltegravir alone or in combination with efavirenz or darunavir. Gut cells were obtained by upper and lower endoscopy with biopsies from duodenum, ileum, colon, and rectum at baseline and 12 weeks. Study outcomes included plasma HIV RNA, HIV DNA and RNA from peripheral blood mononuclear cells (PBMC) and four gut sites, T-cell subsets, and activation markers.

Objective

To determine whether raltegravir-containing antiretroviral therapy (ART) intensification reduces HIV levels in the gut. Design: Open-label study in HIV-positive adults on ART with plasma HIV RNA below 40 copies/ml.

Results

Intensification produced no consistent decrease in HIV RNA in the plasma, PBMC, duodenum, colon, or rectum. However, five of seven participants had a decrease in unspliced HIV RNA per 10 CD4(+) T cells in the ileum. There was a trend towards decreased T-cell activation in all sites, which was greatest for CD8(+) T cells in the ileum and PBMC, and a trend towards increased CD4(+) T cells in the ileum.

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