Experimental Pneumococcal Carriage in People Living With HIV

Characterising Pneumococcal Carriage and Immunity in People Living With HIV in Blantyre, Malawi, Following Experimental Pneumococcal Inoculation

The goal of this experimental pneumococcal carriage study is to to characterise rates and determinants of experimental pneumococcal carriage in PLHIV.

The main questions it aims to answer are:

• can PLHIV be experimentally inoculated with pneumococcus in a safe manner?
• what are the immunological determinants of pneumococcal carriage in PLHIV compared to HIV-negative participants?
• how do the pneumococcal carriage dynamics differ between PLHIV and HIV-negative participants?

Participants will be inoculated intranasally with a controlled concentration of pneumococcus after which they will be monitored for 21 days during which nasal and systemic immune dynamics and pneumococcal carriage dynamics will be evaluated. At the end of the study any participants exhibiting carriage will have the pneumococcus cleared with antibiotics.

Study Overview

• Status: Not yet recruiting
• Conditions: Hiv; Pneumococcus; Pneumonia
• Intervention / Treatment: Other: Streptococcus pneumoniae serotype 6B

Detailed Description

The EHPC has been established at the Malawi-Liverpool Wellcome centre (MLW) and demonstrated acceptability and feasibility in this setting. To date, over 250 participants have been enrolled on the EHPC at MLW without any study complications. Participants will be inoculated in both nostrils with a controlled concentration of penicillin-sensitive Streptococcus pneumoniae. Participants will be followed up for 25 days following inoculation during which sampling will occur at established time-points to establish pneumococcal carriage and immune cell/immunoglobulin dynamics. After 21 days, participants who demonstrate pneumococcal carriage will commence an antibiotic course to clear the bacteria (participants may be advised by the clinical study team to commence antibiotics earlier if they develop any symptoms of pneumococcal disease). Participants will remain under close observation in study accommodation for the first 3 days following inoculation, and will then be monitored daily at home via text message and telephone calls. A final health-check and exit interview will be conducted on day 25 to evaluate participant satisfaction with study participation. The overall objective is to characterise rates and determinants of experimental pneumococcal carriage in PLHIV in Blantyre, Malawi in order to inform vaccine evaluations and vaccine policy.

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Klara Doherty, MBChB; Phone Number: +265885908115; Email: klara.doherty@lstmed.ac.uk

Study Locations

• Malawi
  • Blantyre, Malawi
    • Malawi-Liverpool Wellcome City
    • Contact: Klara Doherty, MBChB; Email: klara.doherty@lstmed.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged 25 to 45 years old
• Fluent spoken and written Chichewa or English
• Able to give informed written consent
• Access to a functional mobile phone
• Establish on antiretroviral therapy for ≥2 years (if PLHIV)
• Viral load below the lower limit of detection (<LDL) at screening (if PLHIV)
• CD4 count over 350 cells/mm³ at screening (if PLHIV)

Exclusion Criteria:

• HIV-associated hospitalisation and/or treatment for major illness in preceding 2 years
• Currently under investigation for HIV-associated weight-loss, chronic diarrhoea, chronic cough, or another unexplained symptom
• Previous illness caused by pneumococcus
• Additional condition or medication impairing immune response or increasing risk of pneumococcal disease
• Living in close contact with an individual vulnerable to pneumococcal disease
• Allergy to penicillin
• Acute illness in 7 days preceding inoculation
• Antibiotic course in last 2 weeks (excluding prophylactic co-trimoxazole in PLHIV)
• Pregnant or trying to conceive
• Involved in another clinical study (unless observational or in follow-up)
• Current regular cigarette smoking (5+ cigarettes per week)
• Natural carrier of pneumococcus serotype 6B at screening visit
• Participants without a guardian

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Inoculation with Streptococcus pneumoniae serotype 6B; Participants will be inoculation with a controlled concentration of full sequenced, fully antibiotic sensitive Streptococcus pneumonia serotype 6B	Other: Streptococcus pneumoniae serotype 6B; A controlled concentration of streptococcus pneumoniae serotype 6B is placed in both nares of participants

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants with pneumococcal carriage in the nasopharynx post-inoculation	Measured by classic culture and PCR-based methods	From inoculation up to 21 days post-inoculation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average pneumococcal carriage density in the nasopharynx post-inoculation	Measured by classic culture and PCR-based methods	From inoculation up to 21 days post-inoculation
Nasal immunoglobulin concentration at baseline	Measured in nasal fluid	Baseline
Change in nasal immunoglobulin concentration following inoculation	Measured in nasal fluid	Baseline to 21 days post-inoculation
Density of immune cells in the nasal mucosa at baseline	Immune cell to epithelial cell ratio measured in nasal mucosal cell samples	Baseline
Change in density of immune cells in the nasal mucosa following inoculation	Immune cell to epithelial cell ratio measured in nasal mucosal cell samples	Baseline up to 21 days post-inoculation
Immune cell activation activation in the nasal mucosa at baseline	Concentration of markers of immune cell activation measured in nasal fluid and cell samples	Baseline
Change in immune cell activation in the nasal mucosa following inoculation	Concentration of markers of immune cell activation measured in nasal fluid and cell samples	Baseline up to 21 days post-inoculation

Collaborators and Investigators

• Sponsor: Liverpool School of Tropical Medicine
• Investigators: Principal Investigator: Stephen Gordon, MA MD, Malawi-Liverpool Wellcome Centre

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2023
• Primary Completion (Anticipated): January 1, 2024
• Study Completion (Anticipated): January 1, 2024

Study Registration Dates

• First Submitted: November 14, 2022
• First Submitted That Met QC Criteria: January 13, 2023
• First Posted (Estimate): January 26, 2023

Study Record Updates

• Last Update Posted (Estimate): January 26, 2023
• Last Update Submitted That Met QC Criteria: January 13, 2023
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia; Lung Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Streptococcal Infections; Gram-Positive Bacterial Infections; Pneumonia, Bacterial; Pneumococcal Infections; Pneumonia, Pneumococcal
• Other Study ID Numbers: EHPC in PLHIV

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No