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

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

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.

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