Tenofovir gel as a rectal microbicide: evidence for protection and priming of T-cell responses in the SIV challenge model
22 September 2008. Related: Transmission.
Richard Jefferys, TAG
The new PLoS Medicine features a study conducted by Martin Cranage and colleagues evaluating tenofovir gel as a potential rectal microbicide in the SIV challenge model. The researchers report that application of the gel two hours prior to exposure to the SIVmac251/32H challenge virus protected six out of nine macaques. Of the remaining three, two showed lowered viral loads post-infection compared to controls. Interestingly, most of the protected animals also displayed detectable SIV-specific T cell responses even though sensitive assays could find no trace of virus.
The PLoS editor’s summary raises the concern that these SIV-specific T cells may be associated with enhanced susceptibility to infection upon re-exposure; however, Cranage et al note in their discussion that transient tenofovir treatment immediately post SIV infection has been shown to lead to induction of SIV-specific T cell responses, and macaques <http://jvi.asm.org/cgi/content/full/75/21/10187> in this study subsequently resisted both homologous and heterologous SIV challenges. The question of whether the SIV-specific T cell responses observed in Cranage’s study have the potential to be protective can only be definitively addressed by another experiment in which the macaques are re-challenged with SIV.
An additional implication of these data is that human trials of microbicides and pre-exposure prophylaxis (PrEP) should include monitoring for HIV-specific T cell responses.
TAG Basic Science Blog 06 Aug 2008
Cranage M et al. Prevention of SIV Rectal Transmission and Priming of T Cell Responses in Macaques after Local Pre-exposure Application of Tenofovir Gel. PLoS Medicine Vol. 5, No. 8, e157 doi:10.1371/journal.pmed.0050157