Clinical Trial: Effect of Schistosomiasis Mansoni on HIV Susceptibility and Female Genital Immunology

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Effect of Schistosomiasis Mansoni and Its Treatment on HIV Susceptibility and Female Genital Immunology

Brief Summary: The aim of this study is to assess the impact of Schistosoma mansoni infection and its treatment on genital immunology and HIV susceptibility in Ugandan women.

Detailed Summary:

Schistosomiasis mansoni is a water-borne disease caused by helminth Schistosoma mansoni (S. mansoni), in which adult worms deposit eggs in mesenteric blood vessels. Schistomiasis prevalence in the fishing communities in East Africa, and particularly in the Lake Victoria region, exceeds 60% and there is overlap in this region with a high prevalence of HIV (29%).

A recent epidemiological study found an association between S. mansoni and HIV infection in adult women residing near Lake Victoria in Tanzania. Furthermore, in primate studies S. mansoni infection was shown to increase susceptibility to SIV infection after rectal (but not intravenous) challenge, implying that S. mansoni might increase HIV susceptibility by altering local mucosal (gut) immunology.

While S. mansoni does not directly infect the genital tract, we hypothesize that the inflammation it causes in the gut may be associated with mucosal inflammation at other sites through activation of common mucosal homing integrins such as a4b7. Therefore in this study we propose to explore whether S. mansoni increases inflammation and/or HIV susceptibility in the endocervix of adult women.

HIV-uninfected adult women from Entebbe, Uganda will be screened for schistosomiasis using a commercial CCA rapid test kit, and infected women who fulfill the study eligibility criteria will be recruited into the study. Kato-Katz microscopy analysis will be performed to assess egg shedding at baseline. Additionally, urine microscopy will be done to screen for Schistosoma hematobium (which can directly involve the genital mucosa). Schistosomiasis treatment will be provided to all participants according to Ugandan clinical guidelines.

Endocervical cytobrush, vaginal SoftCup and blood sample
Sponsor: University of Toronto

Current Primary Outcome:

  • Change in the percentage of endocervical CD4+ T cells susceptible to HIV pseudovirus entry after treatment of schistosomiasis. [ Time Frame: 1 month. ]
    The percentage of endocervical CD4+ T cells per cytobrush infected ex vivo by an HIV pseudovirus construct, as quantified by flow cytometry.
  • Change in the number of endocervical CD4+ T cells susceptible to HIV pseudovirus entry after treatment of schistosomiasis. [ Time Frame: 1 month. ]
    The number of endocervical CD4+ T cells per cytobrush infected ex vivo by an HIV pseudovirus construct, as quantified by flow cytometry.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Change in the percentage of blood CD4+ T cells susceptible to HIV pseudovirus entry after treatment of schistosomiasis. [ Time Frame: 1 and 2 months. ]
    The percentage of blood CD4+ T cells infected ex vivo by an HIV pseudovirus construct, as quantified by flow cytometry.
  • Change in the phenotype of endocervical and blood CD4+ T cells after treatment of schistosomiasis. [ Time Frame: 1 and 2 months. ]
    Surface expression of CCR5, CD69, CD38, HLA-DR, a4b7, CCR7 and CD45RA by endocervical and blood CD4 T will be assessed using flow cytometry.
  • Change in genital proinflammatory cytokine levels after treatment of schistosomiasis. [ Time Frame: 1 and 2 months. ]
    A predefined genital inflammation score based on genital levels of pro-inflammatory cytokines and chemokines [as per Arnold K et al, Muc Immunol, 2015] will be assessed.
  • Change in the cervico-vaginal microbiome after treatment of schistosomiasis. [ Time Frame: 1 and 2 months. ]
    The cervico-vaginal microbiome will be assessed by 16s rRNA sequencing before and after schistosomiasis therapy.
  • Change in the cervico-vaginal proteome after treatment of schistosomiasis. [ Time Frame: 1 and 2 months. ]
    The genital proteome will be assessed by mass spectrometry before and after schistosomiasis therapy.
  • Change in the percentage of endocervical CD4+ T cells susceptible to HIV pseudovirus entry after treatment of schistosomiasis. [ Time Frame: 2 months. ]
    The percentage of endocervical CD4+ T cells per cytobrush infected ex vivo by an HIV pseudovirus construct, as quantified by flow cytometry.
  • Change in the number of endocervical CD4+ T cells susceptible to HIV pseudovirus entry after treatment of schistosomiasis. [ Time Frame: 2 months. ]
    The number of endocervical CD4+ T cells per cytobrush infected ex vivo by an HIV pseudovirus construct, as quantified by flow cytometry.


Original Secondary Outcome: Same as current

Information By: University of Toronto

Dates:
Date Received: August 15, 2016
Date Started: March 2016
Date Completion:
Last Updated: October 26, 2016
Last Verified: October 2016