Intracellular and cell-free (infectious) HIV-1 in rectal mucosa

The intestinal mucosa contains most of the total lymphocyte pool and plays an important role in viral transmission, but only slight attention has been given to the immunological and virological aspects of human immunodeficien cy virus-1 (HIV-1) infection at this site. In this study, before initiating or changing antiretroviral therapy, paired blood samples and rectal biopsi es (RB) were obtained from 26 consecutive HIV-infected subjects. HIV-1 isol ation and biological characterization, DNA, and HIV-1 RNA titration were as sessed, as were in vitro tumor necrosis factor-alpha (TNF-alpha.) and inter leukin-beta (IL-1 beta) spontaneous production. The rate of HIV-1 isolation from peripheral blood mononuclear cells (PBMCs) and RBs was 75% and 58%, r espectively. All RB-derived isolates were nonsyncytium inducing (NSI), inde pendent of the phenotype of blood-derived isolates. Proviral DNA and detect able HIV-1 RNA levels were measured in 100% and 77% of RBs, respectively. A statistical correlation was observed between HIV-1 DNA and HIV-1 RNA level s in rectal mucosa (P = 0.0075), whereas no correlation was found between t hese levels in blood samples (P > 0.05). Antiretroviral treatment did not s eem to influence HIV-1 detection in RBs. Higher levels of in vitro proinfla mmmatory cytokine production were found in the RBs of most infected patient s when compared with healthy controls. Therefore, the rectal mucosa is impo rtant HIV-1 reservoir that demonstrates discordant viral evolution with res pect to blood. Both the virus type and the mucosa pathway of immunoactive s ubstances might have important implications for therapeutic decision-making and monitoring and could influence the bidirectional transmission of HIV-1 in mucosal surfaces. (C) 2001 Wiley-Liss, Inc.