Serological Response to Antipneumococcal Vaccination and Impact on Streptococcus Pneumoniae Nasal Carriage in HIV Adults

HIV Infection Clinical Trial

— PCV13HIV2011  

Official title:

Serological Response to Antipneumococcal Vaccination and Consequent Impact on Streptococcus Pneumoniae Nasal Carriage in HIV Positive Adults: a Prospective Study Using 13-valent Conjugate Vaccine

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02123433
• Other study ID #: 2011-004518-40
• Secondary ID: 2011-004518-40
• Status: Completed
• Phase: Phase 3
• First received: December 13, 2013
• Last updated: April 23, 2014
• Start date: December 2011
• Est. completion date: October 2013

Study information

• Verified date: April 2014
• Source: University of Siena
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: The Italian Medicines Agency
• Study type: Interventional

Clinical Trial Summary

S. pneumoniae is frequently isolated from nasal swabs of healthy subjects, but it can also cause severe diseases (pneumonia, bacteraemia, meningitis and sepsis).HIV-infected subjects are more sensitive to invasive diseases and recurrent infection than the general population. Nasal carriage is the main pathogenetic feature for invasive disease: bacteraemia is more frequent in carriers, HIV+ patients are constantly colonized by the same pneumococcal strain and their nasopharyngeal isolates have features similar to subsequent invasive strains. A 23-valent polysaccharide vaccine (PPV23) has long been available and recommended in the HIV+ population as prophylaxis for invasive disease. Studies regarding efficacy of PPV23 in HIV+ are controversial and highlight that immune response induced by PPV23 in HIV+ is poor and an hyporesponsiveness to repeated polysaccaridic antigens stimulation can occur. Moreover, PPV23 seems not to affect pneumococcal carriage status and could lead to emergence of non-vaccine serotypes. The conjugation of pneumococcal capsular polysaccharides to carrier proteins results in an improved T-cell dependent immune response, characterized by increased antibody concentrations and induction of T and B memory cells, with a demonstrated higher efficacy in children. A heptavalent vaccine conjugated with diphtheria toxoid (PCV7) is approved in Europe since 2001 and is effective in reducing incidence of invasive disease by vaccine serotypes (4, 6B, 9V, 14, 18C, 19F, 23F), in both children and adults, due to effect of herd immunity. A PCV13 formulation has recently been developed, covering PCV7 serotypes plus 1, 3, 5, 6A, 7F and 19A. PCV13 revealed the same safety profile as PCV7 in pediatric patients, that are the main target of conjugate vaccines licensure. Some trials showed a better antibody response in terms of quantity and quality in HIV + adults by using PCV7 as compared to PPV23. However these data were not unequivocally confirmed in further studies on the use of PCV7 alone or in combination with PPV23. The first trials of PCV13 use in adults showed the same or even better response compared to PPV23, with a safety and tolerability similar to PCV7. PCV13 in HIV+ adults is a promising candidate prophylactic measure for pneumococcal infections. The purpose of this study is to evaluate serological response and prevalence of nasopharyngeal colonization by S. pneumoniae in HIV+ non-hospitalized adults, following vaccination with 2 doses of PCV13.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: October 2013
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• > 18 years old

• obtained informed consent

• outpatient

• CD4 =200 cells/µl in the last two evaluations before T0

Exclusion Criteria:

• > 65 years old

• presence of acute infectious disease

• antibiotic therapy (ongoing or in the previous <= 7 days)

• previous PPV23 or PCV7 vaccination

• Pregnancy

• Current immunomodulatory therapy

• Immunosuppression not HIV related

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• HIV Infection
• Infection
• Pneumococcal Infections
• Pneumonia

Intervention

Biological:
• pneumococcal conjugate 13 valent vaccine
Pneumococcal polysaccharide conjugate vaccine(13-valent adsorbed) conjugated to CRM197 carrier protein and adsorbed on aluminum phosphate (0.125 mg of aluminum). Pharmaceutical form: suspension for injection. Dosage: 0.5 ml, containing 2.2 g of polysaccharide for serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 23F, and 4.4 micrograms for serotype 6B. Prevenar 13 is administered in two doses,each of 0.5 ml, with an interval of 2 months, injected intramuscularly in the deltoid muscle of the arm.

Locations

Country	Name	City	State
Italy	Istituto di Clinica delle Malattie Infettive, Policlinico Gemelli	Roma
Italy	UOC Malattie Infettive Universitarie, Policlinico Le Scotte	Siena

Sponsors (2)

Lead Sponsor	Collaborator
University of Siena	Ministry of Education, Universities and Research, Italy

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serological response after 2 doses of PCV13 vaccine.	Measure of serological response after 2 doses of PCV13 vaccine (booster dose after 8 weeks) in HIV+ adults.	Twenty months	No
Primary	Pneumococcal nasopharyngeal colonization	to determine the rate of nasopharyngeal colonization by different pneumococcal serotypes in HIV-positive adults, in relation to baseline antibody titers at T0	Twenty months	No
Secondary	Pneumococcal chemosusceptibility	Number and percentages of antibiotic resistant (including multiresistant) strains	Twenty months	No
Secondary	Molecular epidemiology	Molecular typing combining PFGE (Pulsed Field Gel Electrophoresis), MLST (MultiLocus Sequence Typing) and PCR analysis of bacterial isolates.	Twenty months	No