Development of a rectal sexually transmitted infection - HIV coinfection model utilizing Chlamydia trachomatis and SHIVSF162p3
Rectal sexually transmitted infections (STIs) may increase HIV susceptibility in men who have sex with men (MSM), and Chlamydia trachomatis is prevalent among HIV-positive MSM. To study STIs and HIV infection in MSM, we first evaluated whether cynomolgus macaques can sustain both C. trachomatis and SHIVSF162p3 infections. METHODS: Four SHIVSF162p3 -positive male cynomolgus macaques were used (n = 3 rectally inoculated with 10(6) IFU; n = 1 control). Systemic and rectal SHIV RNA levels and cytokines were measured by real-time PCR and Luminex assays, respectively.
Macaques were successfully Chlamydia infected. Rectal SHIV shedding (P = 0.02 χ(2) ) and levels of G-CSF, IL-1ra, IL-6, IL-8, IFN-γ, and TNF-α (P ≤ 0.01, Mann-Whitney) in rectal secretions increased following infection.
These pilot data successfully demonstrate rectal C. trachomatis-SHIV coinfection in cynomolgus macaques and suggest the feasibility of a rectal C. trachomatis model for SHIV susceptibility and biomedical prevention studies in the context of rectal STIs.
Available from: Richard J Wolitski
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ABSTRACT: Personal lubricant use is common during anal intercourse. Some water-based products with high osmolality and low pH can damage genital and rectal tissues, and the polymer polyquaternium 15 (PQ15) can enhance HIV replication in vitro. This has raised concerns that lubricants with such properties may increase STD/HIV infection risk, although in vivo evidence is scarce. We use a macaque model to evaluate rectal cytotoxicity and SHIV infection risk after use of a highly osmolar (>8,000 mOsm/kg) water-based lubricant with pH of 4.4, and containing PQ15.
Cytotoxicity was documented by measuring inflammatory cytokines and epithelial tissue sloughing during six weeks of repeated, non-traumatic lubricant or control buffer applications to rectum and anus. We measured susceptibility to SHIVSF162P3 infection by comparing virus doses needed for rectal infection in twenty-one macaques treated with lubricant or control buffer 30 minutes prior to virus exposure.
Lubricant increased pro-inflammatory cytokines and tissue sloughing while control buffer (phosphate buffered saline; PBS) did not. However, the estimated AID50 (50% animal infectious dose) was not different in lubricant- and control buffer-treated macaques (p = 0.4467; logistic regression models).
Although the test lubricant caused acute cytotoxicity in rectal tissues, it did not increase susceptibility to infection in this macaque model. Thus neither the lubricant-induced type/extent of inflammation nor the presence of PQ15 affected infection risk. This study constitutes a first step in the in vivo evaluation of lubricants with regards to HIV transmission.
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