Efficacy and safety of the new recombinant subunit vaccine for varicella zoster virus in people living with HIV
| ISRCTN | ISRCTN15045512 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN15045512 |
| Secondary identifying numbers | AIFA_RSO: 697 |
- Submission date
- 13/02/2024
- Registration date
- 05/03/2024
- Last edited
- 05/03/2024
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Infections and Infestations
Plain English Summary
Background and study aims
Herpes zoster (HZ) is a common result of Varicella-Zoster virus reactivation, occurring as a painful rash. Long-lasting neuropathic pain (post-herpetic neuralgia [PHN]) can persist after rash resolution in up to 20% of patients. As cell-mediated immunity is the main defence against herpes zoster, any condition associated with its impairment, including HIV infection, can lead to a higher risk of VZV reactivation. A live attenuated vaccine showed only modest effectiveness and could not be used in immunosuppressed patients.
A new vaccine (HZ/su) named Shingrix achieved outstanding results in preventing both HZ and PHN in diverse immunocompromised categories. To date data regarding HZ/su vaccine use in people living with HIV (PLWHIV) are very limited but still promising. This study will investigate the immunologic response and safety of the HZ/su vaccine in PLWHIV on effective antiretroviral treatment.
Who can participate?
People living with HIV (PLWHIV) aged 18 years and over who are virally suppressed on antiretroviral treatment
What does the study involve?
Participation in the study involves two additional blood samples before the first vaccine dose and 1 month after the second vaccine dose. Moreover, 1 week after both the first and the second dose patients will be given a questionnaire investigating their symptoms (via a phone call). Finally, a follow-up visit assessing possible further adverse events and/or Herpes Zoster episodes will be scheduled 6 months after the second vaccine dose.
What are the possible benefits and risks of participating?
The main benefit will be the understanding of Herpes Zoster recombinant subunit vaccine immunogenicity in people living with HIV. Blood sampling procedures can cause bleeding, bruises, and superficial vein thrombosis (blood clots).
Where is the study run from?
Policlinico Tor Vergata of Rome, Policlinico Umberto I of Rome and San Paolo Hospital of Milan (Italy)
When is the study starting and how long is it expected to run for?
April 2023 to December 2026
Who is funding the study?
1. Società Italiana di Malattie Infettive e Tropicali (SIMIT) (Italy)
2. GlaxoSmithKline (GSK) (UK)
Who is the main contact?
1. Marco Iannetta, marco.iannetta@uniroma2.it
2. Loredana Sarmati, sarmati@med.uniroma2.it
3. Claudio Maria Mastroianni, claudio.mastroianni@uniroma1.it
4. Giulia Carla Marchetti, giulia.marchetti@unimi.it
Contact information
Public, Scientific
Via Montpellier, 1
Rome
00133
Italy
 ORCID ID |
0000-0002-6938-8627 |
|---|---|
| Phone | +39 (0)620903220 |
| marco.iannetta@uniroma2.it |
Principal Investigator
Piazzale Aldo Moro, 5
Rome
00185
Italy
| ORCID ID |
0000-0002-1286-467X |
|---|---|
| Phone | +39 (0)0649973073 |
| claudio.mastroianni@uniroma1.it |
Principal Investigator
Via Montpellier, 1
Rome
00133
Italy
| ORCID ID |
0000-0003-1452-0333 |
|---|---|
| Phone | +39 (0)620908192 |
| sarmati@med.uniroma2.it |
Public, Scientific
Via Antonio di Rudinì, 8
Milan
20142
Italy
| ORCID ID |
0000-0002-4498-4828 |
|---|---|
| Phone | +39 (0)250323396 |
| giulia.marchetti@unimi.it |
Study information
| Study design | Multicentric observational prospective study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Longitudinal study |
| Study setting(s) | Hospital, University/medical school/dental school |
| Study type | Safety, Efficacy |
| Participant information sheet | Not available in web format, please use the contact details to request a participant information sheet |
| Scientific title | Varicella zoster recombinant HZ/su vaccine: immunogenicity and safety in people living with HIV according to LTCD4 count strata |
| Study acronym | HZ/su_PLWHIV |
| Study hypothesis | 1. The HZ/su recombinant vaccine is immunogenic in people living with HIV (PLWHIV) eliciting both humoral and cell-mediated specific immunity with a high vaccine response rate (VRR) in the group of patients on-ART with high LTCD4 cell count, but poorer in those with lower LTCD4. 2. The HZ/su recombinant vaccine is safe and has an acceptable reactogenicity profile in PLWHIV in a real-life scenario, with a potential different grading according to LTCD4 count. |
| Ethics approval(s) |
Approved 26/05/2023, Comitato Etico indipendente Fondazione PTV Policlinico Tor Vergata (Viale Oxford 81, Rome, 00133, Italy; +39 (0)620900035; comitatoetico.lazioarea2@ptvonline.it), ref: 115.23 |
| Condition | Prevention of herpes zoster in people living with HIV |
| Intervention | The present study will investigate the immunologic response and safety of the HZ/su vaccine in PLWHIV on effective antiretroviral treatment, according to the immunological situation. Three infectious disease centers in Italy will participate in the study, prospectively enrolling a total of 500 PLWHIV (250 with current CD4+ T-lymphocyte (LTCD4) counts <350 cell/mm3 and 250 with current LTCD4 ≥350 cells/mm3). A two-dose schedule of Shingrix will be administered to adult PLWHIV (2 months apart), as recommended by national guidelines. Blood samples will be collected at baseline and 1 month after schedule completion. The primary objective of the study is the evaluation of immunogenicity assessed in terms of vaccine response rates (VRR) as in pivotal trials, according to LTCD4 count strata. For humoral response, VRR is defined as a four-fold increase in anti-gE antibodies compared to baseline by ELISA. In a subgroup of 100 patients (50 for each LTCD4 stratum), cell-mediated immunity will be investigated at baseline (M0) and one month (+/- 14 days) after the second HZ/su vaccine dose (M2 +1). |
| Intervention type | Biological/Vaccine |
| Pharmaceutical study type(s) | Not Applicable |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Shingrix |
| Primary outcome measure | HZ/su vaccine immunogenicity will be evaluated through the analysis of humoral immunity and vaccine response rate (VRR) in PLWHIV according to the current LTCD4 absolute count (cells/mm3). To this purpose, anti-glycoprotein E (gE) antibodies concentration will be assessed for the whole population at baseline (M0) and 1 month (± 14 days) after the second Hz/su vaccine dose (M2+1). Humoral vaccine response rate (VRR) is defined as a fourfold increase over baseline (prior to vaccination) anti-gE concentration (mUI/ml). |
| Secondary outcome measures | 1. HZ/su reactogenicity and safety profile verified after each of the two scheduled doses in PLWHIV according to current LTCD4 absolute count (cells/mm3), using a semi-structured questionnaire investigating local and systemic symptoms, 1 week after both the first and the second dose. A follow-up visit assessing possible further adverse events and/or HZ episodes will be scheduled 6 months (±1 month) after HZ/su vaccine dose 2 (M2 +6). 2. HZ/su vaccine immunogenicity evaluated through analysis of cell-mediated immunity and vaccine response rate (VRR) in PLWHIV according to current LTCD4 absolute count (cells/mm3) In a subgroup of 100 patients (50 for each LTCD4 stratum), cell-mediated immunity will be investigated at baseline (M0) and 1 month (+/- 14 days) after the second HZ/su vaccine dose (M2 +1), using an intracellular cytokine staining (ICS) assay for Interferon-gamma, IL-2, TNF-alpha, and an IFN-gamma release assay (IGRA). Cell-mediated vaccine response rate (VRR) is defined as a twofold increase over baseline (prior to vaccination) of gE-specific polypositive LTCD4 (for ICS) and a twofold increase over baseline (prior to vaccination) of gE-specific IFN-gamma production (for IGRA). 3. HZ/su vaccine immunogenicity verified through analysis of humoral and cell-mediated immunity and vaccine response rate (VRR) in PLWHIV according to the current LTCD4/CD8 ratio. In a subgroup of 100 patients (50 for each LTCD4 stratum), cell-mediated immunity will be investigated at baseline (M0) and one month (+/- 14 days) after the second HZ/su vaccine dose (M2 +1), using an intracellular cytokine staining (ICS) assay for Interferon-gamma, IL-2, TNF-alpha, and an IFN-gamma release assay (IGRA). Cell-mediated vaccine response rate (VRR) is defined as a twofold increase over baseline (prior to vaccination) of gE-specific polypositive LTCD4 (for ICS) and a twofold increase over baseline (prior to vaccination) of gE-specific IFN-gamma production (for IGRA). |
| Overall study start date | 01/04/2023 |
| Overall study end date | 31/12/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 100 Years |
| Sex | Both |
| Target number of participants | 500 |
| Participant inclusion criteria | 1. People living with HIV (PLWHIV) ≥18 years old, on antiretroviral treatment, virally suppressed (HIVRNA <50 copies/ml in the last 6 months) 2. Able to provide informed consent 3. Available CD4 cell count in the last 6 months |
| Participant exclusion criteria | 1. Age <18 years old 2. Active herpes zoster episode at enrollment 3. Acute disease/fever at enrollment 4. Known allergy to vaccine component 5. Other than HIV immunosuppressive condition or treatment. Prednisone <20 mg/day, or equivalent, is allowed. Inhaled and topical steroids are allowed 6. Pregnancy 7. Lactation 8. Women planning to become pregnant or planning to discontinue contraceptive methods |
| Recruitment start date | 15/02/2024 |
| Recruitment end date | 15/05/2026 |
Locations
Countries of recruitment
- Italy
Study participating centres
Rome
00133
Italy
Rome
00185
Italy
Milan
20142
Italy
Sponsor information
University/education
Department of Systems Medicine
Via Montpellier, 1
Rome
00133
Italy
| Phone | +39 (0)6209083220 |
|---|---|
| medicinadeisistemi@med.uniroma2.it | |
| Website | https://www-2021.medicinadeisistemi.uniroma2.it/ |
"ROR" |
https://ror.org/02p77k626 |
Funders
Funder type
Research organisation
No information available
Government organisation / For-profit companies (industry)
- Alternative name(s)
- GlaxoSmithKline plc., GSK plc., GSK
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 30/06/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Published as a supplement to the results publication |
| Publication and dissemination plan | 1. EACS abstract 07/24: Reactogenicity 2. CROI abstract 09/24: Preliminary immunological response 3. SIMIT abstract 10/24: Preliminary immunological response 4. Journal of Infectious Diseases/AIDS paper 06/25: Complete results |
| IPD sharing plan | The datasets generated and/or analysed during the current study will be published as a supplement to the results publication |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol file | 14/02/2024 | No | No |
Additional files
Editorial Notes
14/02/2024: Study's existence confirmed by the Agenzia Italiana del Farmaco.
