Development of a pigtail macaque model of sexually transmitted infection/HIV coinfection using Chlamydia trachomatis, Trichomonas vaginalis, and SHIV(SF162P3)

Abstract

Background: Sexually transmitted infections (STIs) are associated with an increased risk of HIV infection. To model the interaction between STIs and HIV infection, we evaluated the capacity of the pigtail macaque model to sustain triple infection with Trichomonas vaginalis, Chlamydia trachomatis, and SHIV(SF162P3).

Methods: Seven SHIV(SF162P3) -infected pigtail macaques were inoculated with T. vaginalis only (n = 2), C. trachomatis only (n = 1), both T. vaginalis and C. trachomatis (n = 2), or control media (no STI; n = 2). Infections were confirmed by culture and/or nucleic acid testing. Genital mucosa was visualized by colposcopy.

Results: Characteristic gynecologic signs were observed for both STIs, but not in control animals. Manifestations were most prominent at days 7-10 post-infection. STIs persisted between 4 and 6 weeks and were cleared with antibiotics.

Conclusions: These pilot studies demonstrate the first successful STI-SHIV triple infection of pigtail macaques, with clinical presentation of genital STI symptoms similar to those observed in humans.

Fig. 1

Relative increase in inflammatory cells in cervical cell collections of sexually transmitted infection (STI)-infected macaques. Analyses were conducted in Chlamydia trachomatis-only (96Po58)- and C. trachomatis + Trichomonas vaginalis–infected macaques (FH3 and 96Po78). 96Po25 received mock media inoculations (control). Cell populations were collected by cervical cytobrush sampling and enumerated by microscopy utilizing an Endtz-trypan differential stain. The graph longitudinally depicts the percent of cervical infiltrate cell types present at baseline and weeks 1–4 post-infection (week 1, relative to first C. trachomatis inoculum). An increase in the percentage of inflammatory cells consisting of polymorphonuclear (PMN) cells and/or total leukocyte infiltrate, relative to baseline, was observed in all three sexually transmitted infection (STI)-infected macaques over the course of the study.

Fig. 2

Cervical colposcopic images of a representative macaque (FH3) (10 × magnification). (A) Cervical mucosa (ectocervix) at baseline, characterized by normal, pink coloration, and presence of scant, clear normal menstrual-related discharge. (B) Cervical mucosa 7 days after administration of 1st Chlamydia trachomatis inoculum (1 × 10⁶ IFU). Erythema, tissue vascularization (arrow), edema, and presence of mucopurulent discharge noted during visual inspection. (C) Cervical mucosa 4 days after administration of second C. trachomatis (1 × 10⁶ IFU) and Trichomonas vaginalis (6 × 10⁶ trichomonads) inoculums; 10 days post-infection, relative to 1st C. trachomatis inoculation. Findings include severe erythema and edema, areas of blistering erosion (arrows), and opaque, bubbly, mucopurulent discharge originating from the cervical os. IFU, inclusion-forming units.

Fig. 3

No impact of sexually transmitted infections on plasma SHIV_SF162P3 RNA levels. No differences in plasma SHIV RNA levels (y-axis) was observed in response to Chlamydia trachomatis (96Po58), Trichomonas vaginalis (TD6 and 96Po17), or C. trachomatis + T. vaginalis infection (FH3 and 96Po78) (Controls: 96Po25 and 96Po26) (x-axis). Threshold sensitivity level = 50 copies per sample. SHIV RNA levels reported at copies per ml plasma. ^†Animal euthanized for reasons unrelated sexually transmitted infection (STI) inoculation/infection.