Experimental Pneumococcal Carriage in People Living With HIV

Liverpool School of Tropical Medicine

Status

Not yet enrolling

Conditions

Pneumococcus; Pneumonia

Hiv

Treatments

Other: Streptococcus pneumoniae serotype 6B

Study type

Interventional

Funder types

Other

Identifiers

NCT05698225

EHPC in PLHIV

Details and patient eligibility

About

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.

Full 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.

Enrollment

150 estimated patients

Sex

All

Ages

25 to 45 years old

Volunteers

Accepts Healthy Volunteers

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