Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202004507940963 Date of Approval: 14/04/2020
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title Immunogenetic Modulators of Mucosal Protection from HIV-1: The Kinga Study
Official scientific title Immunogenetic Modulators of Mucosal Protection from HIV-1
Brief summary describing the background and objectives of the trial A challenge to the development of HIV-1 vaccines is to better understand the natural immune mechanisms for protection from HIV-1 infection. To this end, immunologists have increasingly appreciated the importance of regulatory T cells in peripheral blood that modulate the magnitude and characteristics of the host inflammatory response including against infectious diseases. We have also recently identified specific host genetic variants in the genes CD101 and UBE2V1 that appear to strongly predispose to HIV-1 infection risk and may act through regulatory T cells and other immunologic pathways. Most studies of individuals who are repeatedly HIV-1 exposed but remain seronegative (HESN) have focused on immunological correlates in peripheral blood rather than mucosal immune responses. However, with genital mucosal tissues being the portal of entry for heterosexually transmitted HIV-1 infection, it is critical that we understand the role of immunological responses to HIV-1 that occur in the genital mucosa. A valuable model to carry out such studies is offered by the evaluation of HIV-Exposed SeroNegative (HESN) individuals, particularly in the context of heterosexual sex with a stable HIV-1 infected partner e.g., HIV-1 serodiscordant couples (SDC). In order to understand how genital exposure to HIV-1 may modulate these immune pathways, HIV-1 serodiscordant couples should be compared to heterosexual partners in concordant HIV-1 negative couples (CNC) where neither partner has HIV-1. Here we propose to address this important knowledge gap by enrolling high-risk HESN with defined heterosexual HIV-1 exposures in the context of serodiscordant partnerships compared to unexposed concordant seronegative controls. We will prospectively obtain mucosal and peripheral blood samples for a detailed analysis of longitudinal immune responses, while also collecting samples for genetic characterization to understand how variants in CD101 and UBE2V1 may modulate host mucosal responses a
Type of trial CCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied HIV/AIDS
Purpose of the trial Prevention
Anticipated trial start date 31/08/2018
Actual trial start date 27/09/2018
Anticipated date of last follow up 31/07/2020
Actual Last follow-up date
Anticipated target sample size (number of participants) 812
Actual target sample size (number of participants) 812
Recruitment status Closed to recruitment,follow-up continuing
Publication URL
Secondary Ids Issuing authority/Trial register
ECCT 18 05 02 Pharmacy and Poisons Board, ECCT
0073 3568 Kenya Medical Research Institute SERU
STUDY00001559 University of Washington IRB
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Non-randomised Allocation was determined by the holder of the sequence who is situated off site Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group HIV Prevention This study is a non randomized open label. Interventions are either PrEP (for HIV uninfected) or ART (for HIV infected) 6 months PrEP 406 Uncontrolled
Experimental Group HIV Prevention This study is non randomized that seeks to understand immunity against HIV at the tissue leve. 6 months ART 406
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Inclusion Criteria The partner (HIV-1 uninfected) participants must meet the following criteria (by self-report, unless otherwise indicated) in order to be eligible for inclusion in the study: • Age ≥18 and ≤65 and able to provide independent informed consent for research per local regulations and guidelines • Able and willing to provide written informed consent to be screened for and to take part in the study • Part of a heterosexual couple in which either one or both partners meet the study eligibility criteria for partner (HIV-1 uninfected) participants. Couples are defined by the following criteria: o Partners are sexually active (defined as having had vaginal intercourse with the enrolled partner at least 6 times in the last three months) o Partners plan to remain in the relationship for the duration of the study period. o HIV-1 uninfected status is based on negative HIV-1 rapid tests, at study screening and at the enrollment visit (separate HIV-1 serological testing at both visits must be performed if enrollment is more than 2 weeks after screening) o Able and willing to provide adequate locator information for study retention purposes, as defined by local standard operating procedures Potential partner (HIV-1 uninfected) participants who meet any of the following criteria (by self-report, unless otherwise indicated) will be excluded from the study: • Self-reported use of antiretroviral pre-exposure prophylaxis (PrEP) use prior to enrollment • Active and serious infections, including active tuberculosis infection or osteomyelitis and all infections requiring parenteral antibiotic therapy; active clinically significant medical problems including cardiac disease (e.g., symptoms of ischemia, congestive heart failure or arrhythmia), pulmonary disease (steroid dependent chronic obstructive pulmonary disease), diabetes requiring hypoglycemic medication; and previously diagnosed malignancy expected to require further treatment. Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year,Aged: 65+ Year(s),Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 65 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 13/03/2018 KEMRI SERU
Ethics Committee Address
Street address City Postal code Country
Mbagathi way Nairobi 00100 Kenya
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 26/07/2018 PPB ECCT
Ethics Committee Address
Street address City Postal code Country
Lenana Road Nairobi 00100 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Determination of immunological responses to HIV-1 that occur in the genital mucosa. End of the study
Secondary Outcome Analysis of longitudinal immune responses, while also collecting samples for genetic characterization to understand how variants in CD101 and UBE2V1 may modulate host mucosal responses and HIV-1 infection risk. End of the study
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Partners in Prevention OAU Road Thika Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
National Institutes of Health 3014962563 3015945789 Bethesda United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Fred Hutchinson Cancer Research Center University of Washington 315 9th Avenue Seattle United States of America University
COLLABORATORS
Name Street address City Postal code Country
Kenya Medical Research Institute Mbagathi way Nairobi Kenya
Fred Hutchinson Cancer Research Center University of Washington 15th Avenue Seattle United States of America
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Dr. Nelly Mugo rwamba@uw.edu 0736464299 Ngong Road
City Postal code Country Position/Affiliation
Nairobi Kenya Local Principal Investigator
Role Name Email Phone Street address
Principal Investigator Jairam Lingappa lingappa@uw.edu 2065203822 325 Ninth Avenue
City Postal code Country Position/Affiliation
Seattle United States of America Co Investigator Protocol Chair
Role Name Email Phone Street address
Scientific Enquiries Catherine Kiptinness catherine@pipsthika.org 0736464299 OAU Road
City Postal code Country Position/Affiliation
Thika Kenya Study Coordinator
Role Name Email Phone Street address
Public Enquiries Peter Mogere patandi@pipshika.org 0736464299 OAU Road
City Postal code Country Position/Affiliation
Thika Kenya Regulatory Affairs
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes The study investigators commit to provide this information once the study is complete, analyses done and results published. Study Protocol Sharing will be done once results are published. The results for this study will be publicly available in journals, websites etc. and will be provided by the investigators if requested.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information