期刊
JOURNAL OF INFECTIOUS DISEASES
卷 210, 期 8, 页码 1239-1247出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiu240
关键词
HIV risk; STI or STD; Chlamydia; Trichomonas; menstrual cycle; macaque; HIV susceptibility model
资金
- Centers for Disease Control and Prevention (CDC)
- National Institutes of Health
- CDC [Y1-AI-0681-02]
Background. Sexually transmitted infections (STIs) are associated with an increased risk of human immunodeficiency virus (HIV) infection, but their biological effect on HIV susceptibility is not fully understood. Methods. Female pig-tailed macaques inoculated with Chlamydia trachomatis and Trichomonas vaginalis (n = 9) or medium (controls; n = 7) were repeatedly challenged intravaginally with SHIVSF162p3. Virus levels were evaluated by real-time polymerase chain reaction, plasma and genital cytokine levels by Luminex assays, and STI clinical signs by colposcopy. Results. Simian/HIV (SHIV) susceptibility was enhanced in STI-positive macaques (P = .04, by the log-rank test; relative risk, 2.5 [95% confidence interval, 1.1-5.6]). All STI-positive macaques were SHIV infected, whereas 3 controls (43%) remained uninfected. Moreover, relative to STI-negative animals, SHIV infections occurred earlier in the menstrual cycle in STI-positive macaques (P = .01, by the Wilcoxon test). Levels of inflammatory cytokines (interferon gamma, interleukin 6, and granulocyte colony-stimulating factor [G-CSF]) were higher in STI-positive macaques during STI inoculation and SHIV exposure periods (P <= .05, by the Wilcoxon test). Conclusions. C. trachomatis and T. vaginalis infection increase the susceptibility to SHIV, likely because of prolonged genital tract inflammation. These novel data demonstrate a biological link between these nonulcerative STIs and the risk of SHIV infection, supporting epidemiological assocations of HIV and STIs. This study establishes a macaque model for studies of high-risk HIV transmission and prevention.
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