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A Macaque Model for Rectal Lymphogranuloma Venereum and Non-Lymphogranuloma Venereum Chlamydia trachomatis: Impact on Rectal Simian/Human Immunodeficiency Virus Acquisition

Vishwanathan, Sundaram Ajay PhD*; Aubert, Rachael D. PhD*; Morris, Monica R. BS; Zhao, Chunxia MD; Philips, Christi BS; Khalil, George M. DrPH*; Deyounks, Frank BS; Kelley, Kristen BS§; Ritter, Jana M. DVM; Chen, C.Y. PhD; Kersh, Ellen N. PhD; McNicholl, Janet M. MD*

doi: 10.1097/OLQ.0000000000000644
Original Studies

Background: Sustained genital tract inflammation caused by sexually transmitted infections (STIs) is known to increase risk of vaginal human immunodeficiency virus (HIV) infections but, to our knowledge, there are no nonhuman primate studies that have evaluated its link to rectal HIV acquisition.

Methods: Rhesus macaques inoculated with Chlamydia trachomatis (CT) (serovars LGV-L2 and CT-E; n = 7) or saline (n = 7) received up to 20 rectal challenges twice a week of simian/HIV immunodeficiency virus (SHIVSF162p3). SHIV viremia was determined by real-time PCR and Chlamydia infection by APTIMA Combo 2 testing. The rectal cytokine-chemokine levels were evaluated by multiplex bead assays.

Results: Rectal Chlamydia infection was maintained throughout the study. We did not observe significant differences (P = 1.0) in frequency of SHIV acquisition between the STI and control arms. It took fewer SHIV challenges to infect the STI animals although the difference was not significant (P = 0.59). There were no significant differences in peak plasma viremia between STI and control arms (P = 0.63). The association of plasma viremia with rectal shedding was significantly different by arm (P = 0.038).

Conclusions: In the first such study in a macaque model, we did not observe an increased risk of SHIV acquisition due to rectal Chlamydia coinfection. This macaque model can be further developed and expanded to better investigate the impact of different rectal STIs on HIV acquisition.

Our study in rhesus macaques finds no effect of rectal Chlamydia coinfection on simian/human immunodeficiency virus acquisition.

From the *Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention; †Libra Management Group, ‡Division of Sexually Transmitted Disease Prevention, Centers for Disease Control and Prevention, Atlanta, GA; §The DESA group, Columbia, SC; and ¶Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA

R.D.A. is currently at Division of Foodborne, Waterborne & Environmental Diseases, CDC, Atlanta, GA.

S.A.V., R.D.A., and M.R.M. contributed equally to the study.

Source of support: This work was supported by the Centers for Disease Control and Prevention (CDC) and by the National Institutes of Health and CDC (interagency agreement AAI 12041-001-03000).

Conflict of interest: none declared.

Acknowledgements: The authors thank Dr. David Garber for programmatic support, James Mitchell and Shanon Ellis for animal procedure assistance; our veterinarians and colleagues in the Animal Resources Branch (ARB) for help with macaque-related work; we appreciate Dominique Rollin for providing cell culture controls for IHC; Heather Hayes for histology and immunohistochemistry support; Chi Kai-Hua for PCR support; Dr. John Papp for helpful input and Dr. Tara Henning for sharing the data from her unpublished paper, which informed the design of this study SHIV SF162P3 was obtained through the NIH AIDS Reagent Program, NIAID, NIH from Drs. Janet Harouse, Cecilia Cheng-Mayer, Ranajit Pal, and the DAIDS/NIAID. A portion of the animal studies was funded by an interagency agreement (Y1-A1-0681-02) between CDC and NIH.

Disclaimer: The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the Centers for Disease Control and Prevention or the authors’ affiliated institutions.

R.D.A., E.N.K., S.A.V., J.M.M. conceived and designed the experiments. M.R.M., R.D.A., S.A.V., C.Z., C.P., J.M.R., J.R.P., K.H.C., and C.Y.C. performed the experiments. S.A.V., C.Z., and M.R.M. analyzed the data. S.A.V. wrote the article. G.M.K. participated in the statistical analyses.

Correspondence: Sundaram Ajay Vishwanathan, Division of HIV/AIDS Prevention, NCHHSTP, CDC, Atlanta, GA 30329. E-mail: ile0@cdc.gov.

Received for publication March 9, 2017, and accepted April 20, 2017.

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© Copyright 2017 American Sexually Transmitted Diseases Association