[Show abstract][Hide abstract] ABSTRACT: . HIV-infected individuals demonstrate lower immunogenicity to the influenza vaccine, despite immunologic and virologic control of HIV infection. Obesity has been previously shown to be associated with diminished antibody responses to other vaccines in HIV-uninfected persons. However, no studies have examined if obesity is associated with diminished protective immune response to influenza vaccination among HIV-infected persons on antiretroviral therapy (ART).
. We performed a retrospective analysis of immunogenicity data from a clinical trial of inactivated, trivalent influenza vaccine. The primary endpoint was the proportion of participants with seroconversion, defined as >4-fold increase in anti-hemagglutinin antibody titers after vaccination. Secondary endpoints were the proportion of participants with seroprotection (defined as antibody titers of ≥1 : 40) and geometric mean hemagglutination inhibition antibody titers.
. Overall, 48 (27%) participants were obese (body mass index ≥ 30 kg/m
). Seroconversion rates were comparable between obese and nonobese subjects for all three vaccine strains. Further, postvaccination geometric mean titers did not differ by body mass index category.
. Obesity was not associated with diminished antibody response to influenza vaccination in a sample of healthy HIV-infected persons.
AIDS research and treatment 11/2015; 2015(5):1-7. DOI:10.1155/2015/653840
[Show abstract][Hide abstract] ABSTRACT: We evaluated safety, antiviral, immunomodulatory and anti-inflammatory properties of aprepitant - a neurokinin 1 receptor antagonist.
Phase IB randomized, placebo-controlled, double-blinded study.
Eighteen patients were randomized (nine to aprepitant and nine to placebo). The patients received once-daily treatment (375 mg aprepitant or placebo by oral administration) for 2 weeks and were followed off drug for 4 weeks.
There were no significant changes in the plasma viremia or CD4 T cells during the dosing period. Aprepitant treatment was associated with significant decreases of median within patient change in percentages of CD4 T cells expressing programmed death 1 (-4.8%; P = 0.04), plasma substance P (-34.0 pg/ml; P = 0.05) and soluble CD163 (-563 ng/ml; P = 0.02), with no significant changes in the placebo arm. Mean peak aprepitant plasma concentration on day 14 was 7.6 ± 3.1 μg/ml. The use of aprepitant was associated with moderate increases in total cholesterol, low-density lipoprotein and high-density lipoprotein (median change = +31 mg/dl, P = 0.01; +26 mg/dl, P = 0.02; +3 mg/dl, P = 0.02, respectively).
Aprepitant was safe and well tolerated. At the dose used in this proof-of-concept phase IB study, aprepitant did not show a significant antiviral activity. Aprepitant-treated patients had decreased numbers of CD4 programmed death 1-positive cells and decreased plasma levels of substance P and soluble CD163, suggesting that blockade of the neurokinin 1 receptor pathway has a role in modulating monocyte activation in HIV infection. Prospective studies in virologically-suppressed individuals are warranted to evaluate the immunomodulatory properties of aprepitant. Exposures exceeding those attained in this trial are more likely to elicit clinical benefit.
AIDS 05/2015; 29(8). DOI:10.1097/QAD.0000000000000638 · 5.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Chinese translation BACKGROUND: HIV-infected persons have less robust antibody responses to influenza vaccines. OBJECTIVE: To compare the immunogenicity of high-dose influenza vaccine with that of standard dosing in HIV-positive participants. DESIGN: Randomized, double-blind, controlled trial. (ClinicalTrials.gov: NCT01262846) SETTING: The MacGregor Clinic of the Hospital of the University of Pennsylvania, Philadelphia, from 27 October 2010 to 27 March 2011. PARTICIPANTS: HIV-infected persons older than 18 years. INTERVENTION: Participants were randomly assigned to receive either a standard dose (15 mcg of antigen per strain) or a high dose (60 mcg/strain) of the influenza trivalent vaccine. MEASUREMENTS: The primary end point was the rate of seroprotection, defined as antibody titers of 1:40 or greater on the hemagglutination inhibition assay 21 to 28 days after vaccination. The primary safety end point was frequency and intensity of adverse events. Secondary end points were seroconversion rate (defined as a greater than 4-fold increase in antibody titers) and the geometric mean antibody titer. RESULTS: 195 participants enrolled, and 190 completed the study (93 in the standard-dose group and 97 in the high-dose group). The seroprotection rates after vaccination were higher in the high-dose group for the H1N1 (96% vs. 87%; treatment difference, 9 percentage points [95% CI, 1 to 17 percentage points]; P = 0.029), H3N2 (96% vs. 92%; treatment difference, 3 percentage points [CI, -3 to 10 percentage points]; P = 0.32), and influenza B (91% vs. 80%; treatment difference, 11 percentage points [CI, 1 to 21 percentage points]; P = 0.030) strains. Both vaccines were well-tolerated, with myalgia (19%), malaise (14%), and local pain (10%) the most frequent adverse events. LIMITATIONS: The effectiveness of the vaccine in preventing clinical influenza was not evaluated. The number of participants with CD4 counts less than 0.200 × 109 cells/L was limited. CONCLUSION: HIV-infected persons reach higher levels of influenza seroprotection if vaccinated with the high-dose trivalent vaccine than with the standard-dose. PRIMARY FUNDING SOURCE: National Institute of Allergy and Infectious Diseases and Center for AIDS Research of the University of Pennsylvania.
Annals of internal medicine 01/2013; 158(1):19-26. DOI:10.7326/0003-4819-158-1-201301010-00005 · 17.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Beyond its role in calcium homeostasis, vitamin D plays a critical role in immunological responses to pathogens. We evaluated the relationship between 25-OH vitamin D levels and susceptibility to natural H1N1 infection and H1N1 vaccine responses in HIV infected individuals. METHODS: This was a sub study of an H1N1 vaccine trial conducted at the University of Pennsylvania in 2009/10. We compared the 25-OH vitamin D levels among individuals with and without baseline evidence of prior H1N1 infection and between vaccine responders and non-responders. RESULTS: 120 participants enrolled in the trial, 71% male, 68% African American, median age 46 years. The majority had controlled HIV disease. At baseline, 86% had 25-OH vitamin D levels < 30 ng/ml and 54% had levels < 20 ng/ml. Thirty participants (25%) had evidence of prior H1N1 exposure. There was no difference in mean 25-OH vitamin D levels among patients with or without prior natural H1N1 infection (21 ng/ml vs 20 ng/ml, p=0.72). Among participants without previous H1N1 exposure, only 61% developed protective antibody titers following vaccination. 25-OH vitamin D levels were similar between vaccine responders (20 ng/ml) and non-responders (20 ng/ml) (p=0.83). CONCLUSION: Although 25-OH vitamin D deficiency was very common among HIV-infected individuals, it was not associated with natural susceptibility to H1N1 or to vaccine responses.
Journal of AIDS & Clinical Research 05/2012; 3(4):152. DOI:10.4172/2155-6113.1000152 · 6.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Neurokinin-1 receptor (NK1R) antagonists have anti-HIV activity in monocyte-derived macrophages, decrease CCR5 expression and improve natural killer cell function ex vivo. Aprepitant is a NK1R antagonist approved by FDA as an antiemetic.
We conducted a phase IB randomized, placebo controlled, double masked study to evaluate the safety, antiviral activity, pharmacokinetics and immune-modulatory effects of aprepitant in HIV-infected adults not receiving antiretroviral therapy, with CD4+ cell count ≥350 cells/mm(3) and plasma viral load ≥2,000 copies/ml. Subjects were stratified by viral load (< vs. ≥20,000 copies/ml) and randomized within each stratum to receive aprepitant at 125 mg QD(Low), or 250 mg QD(High), or placebo(PL) for 14 days, and followed for 42 days.
Thirty subjects were randomized and 27 completed treatment (9, 8, 10 subjects in 125 (Low), 250 (High), and PL groups). 63% were male; 37% white; mean (SD) age 43 (9.3) years. Geometric mean baseline viral load (copies/ml) for Low, High, and PL was 15,709, 33,013, and 19,450, respectively. Mean (95%CI) change in log10 viral load at day 14 for Low, High, and PL was -0.02(-0.24,+0.20), -0.05(-0.21,+0.10), and +0.04(-0.08,+0.16), respectively. The number of subjects with AEs was 4(44.4%), 5(62.5%), and 1(10%) for Low, High, and PL. No Grade 4 AEs occurred.
Adverse events of aprepitant were more common in the treated groups. At the dose used in this two-week phase IB study, aprepitant showed biological activity, but no significant antiviral activity.
PLoS ONE 09/2011; 6(9):e24180. DOI:10.1371/journal.pone.0024180 · 3.23 Impact Factor