Mechanisms of Impaired HIV-associated B Cell and Pneumococcal Vaccine Responses

NCT ID: NCT02012309

Last Updated: 2020-11-18

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-08-31
• Study Completion Date: 2021-06-30

Brief Summary

Human Immunodeficiency Virus (HIV) infection is complicated by high rates of infections and cancers which are often the cause of death rather than the HIV/acquired immune deficiency syndrome (AIDS) virus itself. Treatment of HIV with antiretroviral medications has decreased the frequency of many complications by over 90%, but bacterial pneumonia remains extremely high. Current vaccines are not very effective in preventing these infections in patients with HIV infection. The investigators are studying the cells (B cells) that make antibodies to fight infection by binding to and killing bacteria. The goal is to understand how HIV impairs the ability of B cells to make antibodies in sufficient quantity and of sufficient quality to protect patients with HIV to learn how to enhance protection against these infections. The investigators also seek to understand the role of the bacteria (specifically Streptococcus pneumoniae) that normally live in the nose and throat in the development of pneumonia and other infections.

Conditions

HIV; Pneumococcal Infections; Pneumococcal Vaccines

Keywords

HIV; Streptococcus pneumoniae infection; Streptococcus pneumoniae colonization; Pneumococcal vaccines; Prevnar; Pneumovax; Nasopharyngeal microbiome

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

HIV-seronegative

HIV-seronegative subjects will receive Prevnar (PCV-13) at week 0.

Group Type: EXPERIMENTAL

PCV-13

Intervention Type: BIOLOGICAL

HIV-infected

HIV-infected subjects will receive Prevnar (PCV-13) at week 0, and Pneumovax (PPSV-23) at week 8 per Advisory Committee on Immunization Practices (ACIP) guidelines.

Group Type: EXPERIMENTAL

PCV-13

Intervention Type: BIOLOGICAL

PPSV-23

Intervention Type: BIOLOGICAL

Interventions

PCV-13

Intervention Type: BIOLOGICAL

PPSV-23

Intervention Type: BIOLOGICAL

Other Intervention Names

Prevnar; Pneumovax

Eligibility Criteria

Inclusion Criteria

For HIV-infected subjects:

• adults aged 18-55 years
• >200 CD4+ T-cells/microliter
• no antiretroviral therapy (at the time of nasal swab/week 0)
• receiving antiretroviral therapy for >6 weeks (at the time of vaccination/week 12)

For HIV-seronegative controls:

• adults aged 18-55 years

Exclusion Criteria

For all subjects:

• age <18 or >55 years
• history of prior pneumococcal vaccination
• immunosuppressive therapy, defined as: prednisone >15mg/day currently or >14 days in the past 3 months, cytotoxic agents, anti-metabolites, cyclosporine, anti-tumor necrosis factor, B cell monoclonal antibodies
• current or chronic pulmonary infection (bacterial, fungal, mycobacterial), pneumonia, or rhinosinusitis within 2 months
• chronic lung disease
• renal insufficiency, defined as serum creatinine >1.6
• active liver disease, including hepatitis C virus infection
• history of splenectomy
• history of antibacterial therapy within 3 months of nasal swab (week 0)
• current alcohol abuse
• chronic heart disease
• diabetes
• current cigarette smoking

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: collaborator

University of Colorado, Denver

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Edward N Janoff, MD

Role: PRINCIPAL_INVESTIGATOR

University of Colorado-Denver, Denver VA Medical Center

Locations

University of Colorado-Denver

Aurora, Colorado, United States

Denver Health and Hospitals

Denver, Colorado, United States

Denver VA Medical Center

Denver, Colorado, United States

Countries

United States

Other Identifiers

R01AI108479

Identifier Type: NIH

Identifier Source: secondary_id

View Link

13-2405

Identifier Type: -

Identifier Source: org_study_id