Background:  Epidemiologic studies on the aggressive treatment of sexually transmitted infections for the prevention of HIV have yielded confounding results. Here, we demonstrate in an in vitro model of tissue infection that cervical-vaginal lavage specimens (CVL) from women effectively treated for trichomonas infection decrease the susceptibility of cervical explant tissue relative to matched untreated CVL.

Methods: Pretreatment CVL from 8 women with documented trichomonas infection were collected prior to treatment with  2 g metronidazole. CVL were again collected 2 to 3 weeks post-therapy and assessed for trichomonas infection. Pre-and post-therapy CVL (300 mL) were applied to ectocervical, endocervical, and transition zone biopsies obtained from benign hysterectomy specimens. These 4-mm punch biopsies were cultured in a transwell apparatus that maintained the polarity of normal tissue. Tissues were pre-treated (1 hour) with undiluted CVL then infected with 600 TCID₅₀  HIV-1_Bal (R5)  and harvested after 24 hours. Supernatants from the lower chamber of the transwell were added to cMAGI cells to quantify HIV-1 infectivity as a percentage of the positive control (media alone). The CVL were also assessed for the ability to stimulate production TNF-a in a Toll-like receptor 4 (TLR4) responsive HEN mouse spleen cell assay. Toll-like receptor 4 (TLR4) non-responsive HEN mouse spleen cells were used as a negative control.

Results:  Explant cultures from 7 of the 8 women demonstrated 10 to 80% decrease in susceptibility following treatment of trichomonas infection. The percent decrease in susceptibility in 7 of 8 and the percentage increase in susceptibility in 1 of 8 correlated with the change in production of TNF- a in the HEN mouse spleen cell assay (corr coef--0.75) but not in the HEN mouse spleen cell assay.  

Conclusions: Trichomonas is the most common sexually transmitted infection in the United States. CVL from trichomonas infected women increase susceptibility of cervical explant cultures to HIV possibly through a mechanism involving the TLR4. Effective treatment of trichomonas using inexpensive therapy reduces susceptibility to HIV infection by 10 to 80%. Aggressive screening and treatment of Trichomonas-infected women in high HIV risk populations may be an effective and cost-effective HIV-1 prevention strategy.

Keywords: Cervix; trichomonas; susceptibility