Clinical trial NCT02878564: Effect of Schistosomiasis Mansoni on HIV Susceptibility and Female Genital Immunology
Official title: Effect of Schistosomiasis Mansoni and Its Treatment on HIV Susceptibility and Female Genital Immunology
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Schistosomiasis Mansoni
HIV
Keywords: Schistosomiasis mansoni
HIV susceptibility
Genital immunology
Mucosal immunology
HIV entry assay
Adult women
Lead sponsor: University of Toronto
Sponsor class: OTHER
Collaborators: name: UVRI-IAVI HIV Vaccine Program, Uganda
First posted: 2016-08-25
Enrollment: 34
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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 description: 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 samples will be collected at three time points; at baseline and 4 and 8 weeks after schistosomiasis treatment, at the same stage of the menstrual cycle. Using an ex vivo HIV entry assay and mucosal cytokine and microbiome analyses we will quantify the effect of S. mansoni and its treatment on cervical HIV susceptibility and genital inflammation.

Eligibility criteria: Inclusion Criteria:

* Positive (score above "trace") on a urine CCA rapid test
* Willing to be treated with praziquantel
* Willing to give informed consent, and answer short questionnaires on economic status, and sexual risk behavior.
* Willing to comply with the requirements of the protocol
* HIV and classical STI (see below) negative

Exclusion Criteria:

* HIV infected
* Malaria infected
* Pregnant.
* Irregular menstrual cycle, or actively menstruating at the time of genital sampling.
* Tested positive for classical STIs (syphilis, gonorrhea, chlamydia, Trichomonas vaginalis) or having genital ulcers
* Prior hysterectomy
* Deemed by physician to be unlikely to complete study protocol.

Primary outcomes:
measure: Change in the percentage of endocervical CD4+ T cells susceptible to HIV pseudovirus entry after treatment of schistosomiasis.
timeFrame: 1 month.
measure: Change in the number of endocervical CD4+ T cells susceptible to HIV pseudovirus entry after treatment of schistosomiasis.
timeFrame: 1 month.
Secondary outcomes:
measure: Change in the percentage of blood CD4+ T cells susceptible to HIV pseudovirus entry after treatment of schistosomiasis.
timeFrame: 1 and 2 months.
measure: Change in the phenotype of endocervical and blood CD4+ T cells after treatment of schistosomiasis.
timeFrame: 1 and 2 months.
measure: Change in genital proinflammatory cytokine levels after treatment of schistosomiasis.
timeFrame: 1 and 2 months.
measure: Change in the cervico-vaginal microbiome after treatment of schistosomiasis.
timeFrame: 1 and 2 months.
measure: Change in the cervico-vaginal proteome after treatment of schistosomiasis.
timeFrame: 1 and 2 months.
measure: Change in the percentage of endocervical CD4+ T cells susceptible to HIV pseudovirus entry after treatment of schistosomiasis.
timeFrame: 2 months.
measure: Change in the number of endocervical CD4+ T cells susceptible to HIV pseudovirus entry after treatment of schistosomiasis.
timeFrame: 2 months.
Other outcomes:
Locations:
city: Entebbe
country: Uganda
facility: UVRI-IAVI HIV Vaccine program
state: Wakiso
Study officials:
affiliation: University of Toronto
name: Rupert Kaul, MD/PhD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Downs JA, van Dam GJ, Changalucha JM, Corstjens PL, Peck RN, de Dood CJ, Bang H, Andreasen A, Kalluvya SE, van Lieshout L, Johnson WD Jr, Fitzgerald DW. Association of Schistosomiasis and HIV infection in Tanzania. Am J Trop Med Hyg. 2012 Nov;87(5):868-73. doi: 10.4269/ajtmh.2012.12-0395. Epub 2012 Oct 1.
citation: Chenine AL, Shai-Kobiler E, Steele LN, Ong H, Augostini P, Song R, Lee SJ, Autissier P, Ruprecht RM, Secor WE. Acute Schistosoma mansoni infection increases susceptibility to systemic SHIV clade C infection in rhesus macaques after mucosal virus exposure. PLoS Negl Trop Dis. 2008 Jul 23;2(7):e265. doi: 10.1371/journal.pntd.0000265.
citation: Joag VR, McKinnon LR, Liu J, Kidane ST, Yudin MH, Nyanga B, Kimwaki S, Besel KE, Obila JO, Huibner S, Oyugi JO, Arthos J, Anzala O, Kimani J, Ostrowski MA; Toronto HIV Research Group; Kaul R. Identification of preferential CD4+ T-cell targets for HIV infection in the cervix. Mucosal Immunol. 2016 Jan;9(1):1-12. doi: 10.1038/mi.2015.28. Epub 2015 Apr 15.