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Background: Epidemiologic studies associate STIs with increased risk and rates of HIV infection; however few animal model studies demonstrate this association and evaluate underlying biological mechanisms.
Objectives: To evaluate whether other STIs increase susceptibility to HIV infection in a pigtailed macaque model.
Methods: Seven female pigtailed macaques were infected with Trichomonas vaginalis and Chlamydia trachomatis (STIs), 5 macaques received mock STI inoculations, and 2 macaques were untreated controls (n=14, total). All were intravaginally challenged with sub-optimal (10 TCID50) doses of SHIVSF162p3 (simian HIV) in a challenge model mimicking mucosal HIV transmission. STIs were monitored from genital secretions via culture (T. vaginalis) and Gen-Probe assays (C. trachomatis), and clinical manifestations documented by colposcopy. Bi-weekly SHIV RNA levels were measured by reverse-transcriptase, real-time PCR.
Results: STI-inoculated animals became infected and developed clinical signs consistent with these infections. Despite sub-optimal SHIV challenge doses, all 7 (100%) STI-infected animals became SHIV-infected, compared to only 4 of 7 (57%) control animals (p=0.19, Fisher’s exact, two-tailed). Median peak SHIV level of the STI group was significantly higher than controls (Δ=1.3log10; 7.74 vs. 6.40; p=0.008, Wilcoxon). Median SHIV levels at follow-up (weeks 3 -6) differed by a maximum of only 0.8 log10 (week 3).
Conclusions: All STI-treated animals became SHIV-infected, compared to less-than two-thirds of controls, suggesting this model supports epidemiological observations of STI enhancement of HIV risk. Further studies are warranted to define underlying biological mechanisms of the observed enhancement.
Implications for Programs, Policy, and Research: Due to increased STI prevalence in populations at risk for HIV, studies evaluating new HIV preventions should incorporate STI-HIV coinfection animal models. These models will help refine STI treatment guidelines for those at risk for HIV infection, identify mechanisms underlying enhanced HIV susceptibility by STI coinfection, and allow more realistic evaluations of biomedical HIV preventions, such as PrEP and microbicides.