Immune Response to Pneumococcal Vaccination in Aging HIV Positive Adults

Learn more about:
Related Clinical Trial
Changes in Weight, Body Composition and Cardiac Risk After Discontinuing Abacavir Treatment in HIV-infected Individuals Changes in Weight, Body Composition and Metabolic Parameters After Discontinuing Dolutegravir or Tenofovir Disproxil Effect of Berberine on Metabolic Syndrome, Efficacy and Safety in Combination With Antiretroviral Therapy in PLWH. Hemoglobin Level, Coagulopathy Profile and Electrolyte Balance Seronegatives and Metabolic Abnormalities Protocol 2 (SAMA002): Study to Compare the Effect of Kaletra and Combivir® in HIV-Negative Healthy Subjects Myocardial Function & FFA Metabolism in HIV Metabolic Syndrome Exercise and Pioglitazone for HIV-Metabolic Syndromes Observational Study of Changes in Fat Distribution and Blood Metabolites in HIV Infected Adults Yoga for the Management of HIV-Metabolic Syndromes Pravastatin for Hyperlipidaemia in HIV. A Study of Physical and Metabolic Abnormalities in HIV Infected and Uninfected Children and Youth Exercise for Patients With HIV Infections Lactate Metabolism Study in HIV Infected Persons Quality of Life, Sleep, and Biomarkers in People With HIV/AIDS The Effect of Efavirenz and Nelfinavir on the Blood Levels of Certain Lipid-Lowering Drugs Metformin and Rosiglitazone, Alone or in Combination, in HIV-Infected Patients With Insulin and Fat Abnormalities Effects of Treatment Changes on Fat Wasting in the Arms and Legs of HIV Patients Safety Study of Antria Cell Preparation Process to Enhance Facial Fat Grafting With Adipose Derived Stem Cells Growth Hormone Dynamics and Cardiac Steatosis in HIV The Effect of Anti-HIV Treatment on Body Characteristics of HIV-Infected Children Immune Response to Pneumococcal Vaccination in Aging HIV Positive Adults Switching From Zidovudine to an NNRTI or Lopinavir/Ritonavir in Patients Treated With Zidovudine/ Lamivudine/Abacavir. Phase 1 Study to Assess the Safety and Tolerability of TAT4 Gel in Healthy Volunteers Detraining in People Living With HIV/AIDS SHARE: Simple HAART With Abacavir, Reyataz, and Epivir The Effects of Anabolic Steroids and Protease Inhibitors on People Living With HIV/AIDS Observational Study of Fat Loss in HIV Infected Adults Taking Nucleoside Reverse Transcriptase Inhibitors (NRTIs) Metabolism and Body Shape of Healthy Children and Children With Chronic Infections Changing to Nonprotease Inhibitor Treatment to Improve Side Effects Safety and Effectiveness of Fenofibrate and Pravastatin in HIV-Positive Patients With Abnormal Blood Lipids Perceived Changes in Body Build and Image in Patients Who Are Now Taking or Recently Have Stopped Taking Anti-HIV Drugs White Light Scanning to Aid Body Contouring: A Pilot Project Treatment of Abnormal Adipose Tissue Accumulation in Human Immunodeficiency Virus (HIV) Patients The Effect of Low-Dose Human Growth Hormone Therapy in HIV Infected Patients Study Comparing Reducing the Dose of Stavudine Versus Switching to Tenofovir in HIV-Infected Patients Receiving Antiretroviral Therapy The Cleveland Cardiometabolic Cohort Metabolic Abnormalities in HIV-infected Persons Clinical Evaluation of Venus Versa Octipolar Applicator for Reduction of Abdomen Circumference Factors Mediating Gut Microbiota Dysbiosis and Metabolic Disease in HIV Patients. Underlying Abnormalities in Fat and Muscle Leading to Lipodystrophy Syndrome Effects of Short-term Growth Hormone in HIV-infected Patients Safety Study of Filler Agent Composed of Autologous Mesenchymal Stem Cells and Hyaluronic Acid Raltegravir Therapy for Women With HIV and Fat Accumulation The PREFORM Study: A Study to Evaluate the Safety and Efficacy of Rotational Fractional Resection on Submental Contouring Effects of IGF-I in HIV Metabolic Disease Combination of Insulin Sensitizer and Leptin as Treatment for the HAART -Induced Metabolic Syndrome Effectiveness of Nucleoside Supplementation or Switch to Tenofovir in Reversing Fat Loss in HIV Infected Adults Lopinavir/r Monotherapy Versus Abacavir/Lamivudine and Lopinavir/r for Limb Fat Recovery in Persons With Lipoatrophy Effects of Growth Hormone Releasing Hormone in HIV A Study of Increased Lactic Acid and Abnormal Fat Distribution in HIV-Positive Patients Effects of a Uridine Supplement on HIV Infected Adults With Lipoatrophy Body Composition and Adipose Tissue in HIV Study to Evaluate Changes in Limb Fat When Switching From a Thymidine Analogue CONFORM: Rotational Fractional Resection for Submental Contouring Study of Alpha-2 Adrenergic Receptor Dysfunction in Regional Lipoatrophy TH9507 in Patients With HIV-Associated Lipodystrophy TH9507 Extension Study in Patients With HIV- Associated Lipodystrophy Study Evaluating the Impact on Fat Distribution of Nucleoside Reverse Transcriptase Inhibitor (NRTI)-Sparing Regimens in Antiretroviral Experienced Patients With Lipoatrophy Energy Expenditure of People Living With HIV/AIDS Beneficial Effect of Insulin Glulisine by Lipoatrophy and Type 1 Diabetes (LAS) Egrifta Replacement and Sleep Disordered Breathing Clinical Trial to Determine the Efficacy of Sculptra™ Dermal Filler for the Correction of Contour Deformities Caused by Lipoatrophy Clinical Trial to Assess the Effect of the Change of Efavirenz (EFV) for Lopinavir/Ritonavir (LPV/r) in Lipoatrophy in HIV-infected Patients Low Energy Diet and Familial Partial Lipodystrophy Clinical Protocol to Investigate the Efficacy of Recombinant Human Leptin (Metreleptin) in Nonalcoholic Steatohepatitis (NASH) or Nonalcoholic Fatty Liver Disease (NAFLD) Associated With Lipodystrophy A Study to Determine How and Why HIV-Infected Subjects on Anti-viral Treatment Develop Lipodystrophy Adipocyte, Insulin-resistance and Immunity : Evaluation of Interleukin-7 in Lipodystrophy, Diabetes and Obesity Compassionate Use of Metreleptin in Previously Treated People With Generalized Lipodystrophy Role of the Autonomic Nervous System in HIV-Lipodystrophy Leptin for Abnormal Lipid Kinetics in HIV Lipodystrophy Syndrome Therapeutic Approaches to HAART-Induced Lipodystrophy Different Surgical Modalities for Thigh Lipodystrophy Including Liposuction,Thigh Lift and Liposuction Assisted Thigh Lift Leptin to Treat Lipodystrophy Compassionate Use of Metreleptin in Previously Treated People With Partial Lipodystrophy Prevalence of Lipodystrophy Syndrome and Its Role as Cause of Metabolic Disturbances Efficacy, Safety and Tolerability of ISIS 304801 in People With Partial Lipodystrophy With an Open-Label Extension Shock Waves for Treatment of Gynoid Lipodystrophy and Localized Fat Corticosteroid-induced Lipodystrophy and Adipokines Short-term Effects of Leptin in People With Lipodystrophy Leptin to Treat Lipodystrophy Lipodystrophy Connect Patient Registry An Open-Label Treatment Protocol to Provide Metreleptin for the Treatment of Diabetes Mellitus and/or Hypertriglyceridemia Associated With Lipodystrophy Autologous Adipose-Derived Stem Cell Transplantation in Patients With Lipodystrophy

Brief Title

Immune Response to Pneumococcal Vaccination in Aging HIV Positive Adults

Official Title

Immune Response to Pneumococcal Vaccination in Aging HIV Positive Individuals

Brief Summary

      The investigators hypothesized that pneumococcal vaccination with either the 23-valent
      pneumococcal polysaccharide vaccine PPV-23 (Pneumovax-23) alone or the 13-valent pneumococcal
      conjugate vaccine PCV-13 (Prevnar-13) followed by PPV-23 results in a similar antibody
      levels/functional antibody activity and induce similar pneumococcal polysaccharide
      (PPS)-specific B cell response in HIV positive individuals > 50 years of age, HIV positive
      individuals 21-40 years of age as compared to HIV negative > 50 years of age. The
      investigators immunized the study groups HIV+ persons >50, HIV+ persons 21-40 and controls
      (HIV negative) with PCV 13 followed by PPV23 and HIV>50 with PPV alone and examined immune
      responses to polysaccharide (PPS) 23 (F),14, 3, 7 (F) and 19 (A) using polysaccharide
      specific ELISA and opsonophagocytic assays (OPA). Pre- and post-immunization peripheral blood
      samples were obtained. Extensive B cell phenotype analysis using fluorescent antibodies was
      used to characterize PPS-labeled B cells. Specific phenotypes were correlated with antibody
      levels and OPA and compared to populations immunized with PPV
    

Detailed Description

      The purpose of this study is to learn more about how older people with HIV respond to the
      pneumococcal or pneumonia vaccine. Pneumonia occurs very frequently in in older persons AND
      in persons who are infected with HIV. Therefore, it is common practice to vaccinate against
      pneumonia in these patient populations. Because older patients with HIV fit both of these
      categories, it is believed that they are at an increased risk of pneumonia.

      There are two types of pneumonia vaccines available for adults approved by the Federal Drug
      Administration (FDA). One is called the pneumococcal polysaccharide vaccine (PPV23) and
      protects against 23 different strains of the pneumonia bacteria. The other type of vaccine
      called the pneumococcal conjugate vaccine (PCV13) protects against different strains of the
      pneumonia bacteria.

      Until 2012, it was recommended that all HIV-positive adults receive PPV23 when diagnosed with
      HIV and again 5 years later. More recently, the guidelines have changed to all HIV-positive
      adults are to receive PCV13, followed later with PPV23. At this point in time, it is not
      clear which regimen works better in aging HIV positive adults. Investigators are doing this
      study to compare the effectiveness of each vaccine regimen in aging HIV positive adults
      compared to healthy adults. Although several studies show short-term efficacy or increased
      antibody response in HIV+ persons with this vaccine, others do not, in either HIV+ population
      or in elderly. Large efficacy trials necessary to establish clinical superiority of PCV
      compared to PPV will likely not be conducted, particularly in the aging HIV+ population. It
      is therefore essential to define immune responses to conjugated and free-polysaccharide
      preparations by examining traditional antibody and functional levels as well as B cell
      subsets, critically affected by aging and HIV. Will either PCV or PPV elicit an immune
      response compatible with protection in this population? Based on persistent B cell
      perturbations in HAART-treated persons, it is hypothesized that immunization of aging HIV+
      persons with PPV23 will be as effective as a PCV13 containing regimen on a quantitative,
      qualitative, B and T cell level and that the magnitude of this response will be related to
      the degree of chronic inflammation. The proposed studies are highly significant as they will
      define the B and T cell responses to a TI-2 and T-cell dependent form of pneumococcal vaccine
      in the aging HIV+ population. These data will provide the necessary basis for development of
      a rational vaccination approach, including the potential use of novel adjuvant. In this study
      the investigators will:

        1. Test the hypothesis that vaccination with either PPV alone (TI-2) or a PCV containing
           regimen (TD) results in similar antibody levels/functional activity, that are determined
           by levels of chronic inflammation in aging HIV+. The investigators will immunize the
           study group HIV+ persons 50-65 and controls (HIV+21-40 and HIV- 50-65 years) with PCV13
           followed by PPV23 and HIV+ 50-65 and HIV- 50-65 with PPV alone. The investigators will
           examine immune responses to pneumococcal polysaccharides (PPS) 23 (F), 14, 3, 7 (F) and
           19 (A) on a quantitative and qualitative level using ELISA and opsonophagocytic assays
           (OPA) and correlate the response to the degree of inflammation measured in each
           participant.

        2. To test the hypothesis that the levels of antigen specific B cells identified with PPS
           will be comparable between the PPV and PCV vaccine recipients. Pre- and
           post-immunization peripheral blood samples will be obtained. Extensive phenotype
           analysis using antibodies against cluster of differentiation (CD)19, 20, 21, 27, 38, 40,
           immunoglobulin M (IgM) , B-cell activating factor (BAFF), trans-membrane activator and
           calcium modulator and cyclophilin ligand interactor (TACI), and B-cell maturation
           antigen (BCMA) markers will be used to characterize PPS-labeled B cells. Specific
           phenotypes will be correlated with antibody levels, OPA and inflammatory markers and
           compared to the control populations immunized with PPV.
    

Study Phase

Early Phase 1

Study Type

Interventional


Primary Outcome

Antibody response

Secondary Outcome

 PPS-specific B cell phenotype

Condition

HIV Lipodystrophy

Intervention

Pneumococcal polysaccharide vaccine 23 valent

Study Arms / Comparison Groups

 HIV+ 50-65, CD4>200 PCV/PPV
Description:  HIV+ individuals , 50-65 years of age with a nadir cluster of differentiation (CD) 4 count >200 to receive PCV13 vaccine followed 8 weeks later by PPV23
Intervention: 13 valent Pneumococcal conjugate vaccine (PCV13) followed 8 weeks later by 23 valent pneumococcal polysaccharide vaccine

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

160

Start Date

September 1, 2015

Completion Date

March 30, 2020

Primary Completion Date

March 30, 2020

Eligibility Criteria

        Inclusion Criteria:HIV+ 21-40 years of age HIV+ 50-65 years of age HIV- 50-65 years of age

        -

        Exclusion Criteria:

          -  Previous immunization with pneumococcal vaccine less than 5 years ago

          -  pregnancy and absence of contraceptive practice in women of childbearing age and
             breast feeding

          -  known anaphylaxis, hypersensitivity to the pneumonia vaccine

          -  those who received blood products or gammaglobulin in last 3 months

          -  inability to comprehend or sihn informed consent

          -  Medications known to affect immune function (chemotherapy, an
             angiotensin-converting-enzyme (ACE) inhibitors, corticosteroids, anti-TNFalpha agents)

          -  previous disease/present illness that may affect response to vaccination: previous
             pneumococcal disease, removal of spleen, auto-immune disease, end stage renal disease
             (ESRD) or end stage liver disease, cancer)

          -  significant (3x upper limit of normal) in complete blood count (CBC), chemistries,
             immunoglobulin levels
      

Gender

All

Ages

21 Years - 65 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

Maria A. Julia Westerink, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT03039491

Organization ID

MUSC vaccine study


Responsible Party

Sponsor

Study Sponsor

Medical University of South Carolina


Study Sponsor

Maria A. Julia Westerink, MD, Principal Investigator, Medical University of South Carolina


Verification Date

June 2020