Based on the assumption that plasma might not reflect changes elsewhere in the body, especially in the lymphoid tissues, the authors analyzed the effects of 12 weeks of ART intensification with raltegravir (RLG) alone or in combination with efavirenz (EFV) or darunavir (DRV) in 7 patients at different levels in the gut.
These patients had a median duration of HIV infection of 14.5 years, median entry CD4 of 473/mm3, and undetectable viremia <40 c./ml for 2.8 to 12 years (median level: 2.3 c/ml). Five patients were intensified with RLG only.
Intensification resulted in no consistent decrease in plasma HIV RNA.
Unspliced HIV RNA was detectable at baseline in PBMC of all patients, with no consistent changes during intensification.
Cell associated DNA was detectable in blood in all cases at baseline, with a median at 6902 c./million CD4, and decreased in 2 patients during intensification.
From week 0 to week 12, five of seven participants had a decrease in unspliced RNA/million CD4 in the terminal ileum. On the other side, no changes in HIV DNA were detectable in each gut site (ileum, rectum) nor PBMC.
Intensification resulted in a trend towards decreased activation of CD4 and CD8 T cells in all gut sites.
This study is the first to demonstrate different tissue changes, according to gut location, during an intensification trial. In the ileum, which had the highest baseline HIV unspliced RNA and RNA/DNA ratio, the unspliced RNA/million CD4 decreased in 5 out of 7 participants.