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Intensifying treatment does not reduce HIV reservoirs, but gut immune responses may have a role to play

Richard Jefferys, TAG

A study led by Hiroyu Hatano from Steve Deeks’s group at UCSF reports that adding the integrase inhibitor raltegravir (Isentress) to a standard antiretroviral (ART) regimen failed to reduce residual HIV replication, or the HIV reservoir, in a group of individuals with suboptimal CD4 count increases despite prolonged HIV suppression. The intensification approach also did not significantly increase CD4 T cell counts or reduce levels of immune activation, which the authors note adds to the evidence that low-level HIV replication is unlikely to be a major cause of suboptimal CD4 T cell gains in people on ART. [1, 2]

Interestingly, a secondary analysis–conducted in collaboration with Barbara Shacklett’s laboratory at UC Davis–revealed a novel association between the magnitude of HIV Gag-specific CD8 T cell responses in gut-associated lymphoid tissue (GALT) and the size of the HIV reservoir (as measured by proviral DNA in peripheral blood mononuclear cells). Hatano and colleagues caution that the findings are preliminary and require confirmation by larger studies, but also write: “approaches aimed at expanding HIV-specific CD4+ and CD8+ T cell responses in the gut mucosa may accelerate clearance of the viral reservoir. The next logical step would be to pursue therapeutic vaccine studies using HIV vaccines that elicit strong mucosal T cell responses in HAART-treated patients.”

Coincidentally, a paper that appeared online today in the journal Blood describes an approach to augmenting HIV-specific CD8 T cell immunity in GALT. [3]

The researchers sampled HIV-specific CD8 T cells from individuals on ART, expanded them in the laboratory, and then re-infused them. Persistence up to 84 days was documented, as well as trafficking to GALT. Many of the cells displayed a “central memory” phenotype, which is believed to be important due to the ability of these cells to self-renew and proliferate robustly upon encountering antigen. Although the infusion approach has practical limitations, the study authors suggest that their results imply that vaccination strategies aiming to boost systemic and GALT HIV-specific CD8 T cell responses are worth pursuing.

Source: TAG basic scieince blog (21 Mar 2011)

http://tagbasicscienceproject.typepad.com/tags_basic_science_vaccin/2011/03/intensifying-treatment-does-not-reduce-hiv-reservoirs-but-gut-immune-responses-may-have-a-role-to-pl.html

References:

  1. Hatano H et al. A randomized, controlled trial of raltegravir intensification in antiretroviral-treated, HIV-infected patients with a suboptimal CD4+ T cell response. J Infect Dis. (2011) 203 (7): 960-968. doi: 10.1093/infdis/jiq138
    http://jid.oxfordjournals.org/content/203/7/960.abstract
  2. Schulze zur Wiesch J et al. Hide and seek… can we eradicate HIV by treatment intensification? J Infect Dis. (2011) 203 (7): 894-897. doi: 10.1093/infdis/jiq150
    http://jid.oxfordjournals.org/content/203/7/894.extract
  3. Chapuis AG et al. HIV-specific CD8+ T cells from HIV+ individuals receiving HAART can be expanded ex vivo to augment systemic and mucosal immunity in vivo. Blood, prepublished online March 21, 2011; DOI 10.1182/blood-2010-11-320226.
    http://bloodjournal.hematologylibrary.org/cgi/content/abstract/blood-2010-11-320226v1



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