Lack of Compartmentalization Between Gut and Peripheral Blood
In an effort to address the potential role that the gut mucosa plays as a viral reservoir, HIV-1 sequences derived from 2 different gut sites (colon and terminal ileum) and peripheral blood of patients with chronic HIV-1 infection were compared.
This study is reported in the July 15, 2011 issue of the Journal of Infectious Diseases (1).
A total of 20 HIV-infected subjects were studied: 10 patients on ART with undetectable (<50 copies/ml) plasma viremia for more than 1 year, and 10 patients with detectable viremia.
In the aviremic group: HIV DNA was detected in all gut and PBMC specimens; HIV RNA was detected in 20-40% of the gut samples and 80% of PBMCs.
No association was found between the ability to detect HIV RNA by PCR in the gut and the duration of viral suppression in plasma.
In viremic patients: HIV DNA was detected in all gut and PBMC specimens (except 1 ileum sample); HIV RNA was detected in 94% of the gut samples and 88% of PBMCs.
No differences were found between groups when the levels of HIV DNA were compared in the gut or in the PBMCs. There was a trend towards a 10 fold increase of HIV DNA levels in ileum compared to colon in the aviremic patients, that did not reach statistical significance.
In group 2 (viremic patients), HIV-1 variants detected in the gut were genetically indistinguishable from those in the plasma from matching time points. HIV-1 sequences detecetd in the colon and ileum were genetically indistinguishable.
The genetic diversity of HIV DNA was not statistically different for the gut and peripheral blood, both in aviremic and viremic patients.
The genetic diversity of HIV RNA was not statistically different for the gut and peripheral blood, both in aviremic and viremic patients.
The genetic diversity of HIV DNA was not statistically different between colon and ileum, both in aviremic and viremic patients.
The genetic diversity of HIV RNAwas not statistically different between colon and ileum, both in aviremic and viremic patients.
In conclusion, this study through sequence analysis of the env C2-V3 region clearly demonstrated a lack of compartmentalization of HIV-1 quasispecies between blood and gut. It argues for a notion of equilibrium between these 2 compartments. These data indicate that the gut mucosa does not appear to serve as a sanctuary site for HIV-1 replication and that free exchange of HIV-infecetd cells takes place between gut and blood.
1-Imamichi H, DeGray G, Dewar RL et al. Lack of Compartmentalization of HIV-1 Quasispecies Between the Gut and Peripheral Blood Compartments. J Infect Dis 2011; 204: 309-14
Key words: HIV gut reservoir, hiv gut, hiv reservoirs, hiv sanctuary site