Effect of Schistosomiasis Mansoni on HIV Susceptibility and Female Genital Immunology

NCT02878564 | Completed Phase 4

• 1 other identifier: UT-Schisto
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

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.

Conditions

Schistosomiasis Mansoni; HIV

Keywords

Schistosomiasis mansoni; HIV susceptibility; Genital immunology; Mucosal immunology; HIV entry assay; Adult women

Outcome Measures

Primary Outcomes (2)

• Change in the percentage of endocervical CD4+ T cells susceptible to HIV pseudovirus entry after treatment of schistosomiasis.

  The percentage of endocervical CD4+ T cells per cytobrush infected ex vivo by an HIV pseudovirus construct, as quantified by flow cytometry.

  1 month.

• Change in the number of endocervical CD4+ T cells susceptible to HIV pseudovirus entry after treatment of schistosomiasis.

  The number of endocervical CD4+ T cells per cytobrush infected ex vivo by an HIV pseudovirus construct, as quantified by flow cytometry.

  1 month.

Secondary Outcomes (7)

• Change in the percentage of blood CD4+ T cells susceptible to HIV pseudovirus entry after treatment of schistosomiasis.

  1 and 2 months.

• Change in the phenotype of endocervical and blood CD4+ T cells after treatment of schistosomiasis.

  1 and 2 months.

• Change in genital proinflammatory cytokine levels after treatment of schistosomiasis.

  1 and 2 months.

• Change in the cervico-vaginal microbiome after treatment of schistosomiasis.

  1 and 2 months.

• Change in the cervico-vaginal proteome after treatment of schistosomiasis.

  1 and 2 months.

Study Arms (1)

Praziquantel treatment

EXPERIMENTAL

Participants will be HIV-uninfected women with asymptomatic Schistosoma mansoni infection; the study will examine the impact of standard praziquantel therapy (40 mg/kg po single dose) on genital immunology and HIV susceptibility.

Drug: Praziquantel

Interventions

Praziquantel DRUG

40 mg/kg, PO (orally administered tablets)

Also known as: Agopraz, bromoxel, biltricide

Praziquantel treatment

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Toronto: lead
• UVRI-IAVI HIV Vaccine Program, Uganda: collaborator

Study Sites (1)

UVRI-IAVI HIV Vaccine program

Entebbe, Wakiso, Uganda

Location

Related Publications (4)

• Arnold KB, Burgener A, Birse K, Romas L, Dunphy LJ, Shahabi K, Abou M, Westmacott GR, McCorrister S, Kwatampora J, Nyanga B, Kimani J, Masson L, Liebenberg LJ, Abdool Karim SS, Passmore JA, Lauffenburger DA, Kaul R, McKinnon LR. Increased levels of inflammatory cytokines in the female reproductive tract are associated with altered expression of proteases, mucosal barrier proteins, and an influx of HIV-susceptible target cells. Mucosal Immunol. 2016 Jan;9(1):194-205. doi: 10.1038/mi.2015.51. Epub 2015 Jun 24.

  PMID: 26104913 BACKGROUND

• 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.

  PMID: 23033399 BACKGROUND

• 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.

  PMID: 18648516 BACKGROUND

• 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.

  PMID: 25872482 BACKGROUND

MeSH Terms

Conditions

Schistosomiasis mansoni

Interventions

Praziquantel

Condition Hierarchy (Ancestors)

Schistosomiasis; Trematode Infections; Helminthiasis; Parasitic Diseases; Infections; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Rupert Kaul, MD/PhD

  University of Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 15, 2016
• First Posted: August 25, 2016
• Study Start: March 1, 2016
• Primary Completion: October 1, 2016
• Study Completion: October 1, 2016
• Last Updated: October 27, 2016

Record last verified: 2016-10

Data Sharing

• IPD Sharing: Will not share

Locations

UG (1)