scholarly journals A Randomized, Double-blinded, Placebo-controlled Trial of Sitagliptin for Reducing Inflammation and Immune Activation in Treated and Suppressed Human Immunodeficiency Virus Infection

2018 ◽  
Vol 69 (7) ◽  
pp. 1165-1172 ◽  
Author(s):  
Michael P Dubé ◽  
Ellen S Chan ◽  
Jordan E Lake ◽  
Brett Williams ◽  
Jennifer Kinslow ◽  
...  

Abstract Background Dipeptidyl peptidase-4 (DPP-4) inhibitors have pleotropic anti-inflammatory and immune regulatory effects in addition to glucoregulation. We evaluated inflammation and immune markers in suppressed human immunodeficiency virus (HIV) infection during treatment with the DPP-4 inhibitor sitagliptin. Methods Virologically suppressed adults with HIV without diabetes on stable antiretroviral therapy (ART) with ≥100/μL CD4 cells were randomized to 16 weeks of sitagliptin 100 mg/day vs placebo in a multicenter trial. The primary endpoint was the change in plasma soluble CD14 (sCD14) from baseline to week 15–16. Results Ninety participants were randomized, and 42 from each arm were included in per-protocol analyses. Participants were 45% non-Hispanic white, 38% non-Hispanic black, and 15% Hispanic, with a median age of 51 years; 83% were male; and the median CD4 count was 602 cells/μL. At week 15–16, there was no difference in sCD14 change between the 2 arms (P = .69). Relative to placebo, the sitagliptin arm had 47% greater decline in CXCL10 (95% confidence interval, –57% to –35%) at week 15 (P < .001). There were no significant between-arm differences in other soluble biomarkers, total CD4 and CD8 counts, or markers of lymphocyte or monocyte activation. Sitagliptin was well tolerated. Conclusions Sixteen weeks of sitagliptin had no effect on sCD14 levels in virologically suppressed participants with HIV. CXCL10, a chemokine involved in atherogenesis that predicts non-AIDS events during ART, declined markedly with sitagliptin. This suggests that DPP-4 inhibition has the potential to reduce cardiovascular morbidity in treated HIV infection. Clinical Trials Registration NCT01426438.

1987 ◽  
Vol 1 (3) ◽  
pp. 381-395 ◽  
Author(s):  
Beverly Ryan ◽  
Edward Connor ◽  
Anthony Minnefor ◽  
Frank Desposito ◽  
James Oleske

2020 ◽  
Vol 18 (5) ◽  
pp. 381-386
Author(s):  
Yusuke Yoshino ◽  
Ichiro Koga ◽  
Yoshitaka Wakabayashi ◽  
Takatoshi Kitazawa ◽  
Yasuo Ota

Background: The change in the prevalence of hypogonadism with age in men with human immunodeficiency virus (HIV) infection is subject to debate. Objective: To address this issue, we diagnosed hypogonadism based on serum levels of free testosterone (fTST) rather than total testosterone which is thought to be an inaccurate indicator. We also determined the relationship between age and fTST levels and identified risk factors for hypogonadism in men with HIV infection. Method: We retrospectively reviewed fTST levels and associated clinical factors in 71 wellcontrolled HIV-infected men who were treated at Teikyo University Hospital between April 2015 and March 2016 and who had data available on serum fTST levels, measured >6 months after starting antiretroviral therapy. fTST was measured using radioimmunoassay on blood samples collected in the morning. Risk factors for hypogonadism were identified using Welch’s t-test and multiple regression analysis. Results: The men had a mean (± standard deviation) age of 47.4 ± 13.6 years, and mean (± standard deviation) serum fTST level of 13.0 ± 6.1 pg/mL. Fifteen (21.1%) men had hypogonadism based on a fTST <8.5 pg/mL. Serum fTST levels significantly decreased with age (−0.216 pg/mL/year). Older age and low hemoglobin levels were identified as risk factors for hypogonadism. Conclusion: The men in the study experienced a more rapid decline in fTST levels with age than men in the general population (−0.161 pg/mL/year). Serum fTST levels in men with HIV infection should be monitored, especially in older men and those with low hemoglobin levels.


Author(s):  
Sylvia M LaCourse ◽  
Barbra A Richardson ◽  
John Kinuthia ◽  
A J Warr ◽  
Elizabeth Maleche-Obimbo ◽  
...  

Abstract Background Human immunodeficiency virus (HIV)–exposed uninfected (HEU) infants in endemic settings are at high risk of tuberculosis (TB). For infants, progression from primary Mycobacterium tuberculosis (Mtb) infection to TB disease can be rapid. We assessed whether isoniazid (INH) prevents primary Mtb infection. Methods We conducted a randomized nonblinded controlled trial enrolling HEU infants 6 weeks of age without known TB exposure in Kenya. Participants were randomized (1:1) to 12 months of daily INH (10 mg/kg) vs no INH. Primary endpoint was Mtb infection at end of 12 months, assessed by interferon-γ release assay (QuantiFERON-TB Gold Plus) and/or tuberculin skin test (TST, added 6 months after first participant exit). Results Between 15 August 2016 and 6 June 2018, 416 infants were screened, with 300 (72%) randomized to INH or no INH (150 per arm); 2 were excluded due to HIV infection. Among 298 randomized HEU infants, 12-month retention was 96.3% (287/298), and 88.9% (265/298) had primary outcome data. Mtb infection prevalence at 12-month follow-up was 10.6% (28/265); 7.6% (10/132) in the INH arm and 13.5% (18/133) in the no INH arm (7.0 vs 13.4 per 100 person-years; hazard ratio, 0.53 [95% confidence interval {CI}, .24–1.14]; P = .11]), and driven primarily by TST positivity (8.6% [8/93] in INH and 18.1% [17/94] in no INH; relative risk, 0.48 [95% CI, .22–1.05]; P = .07). Frequency of severe adverse events was similar between arms (INH, 14.0% [21/150] vs no INH, 10.7% [16/150]; P = .38), with no INH-related adverse events. Conclusions Further studies evaluating TB preventive therapy to prevent or delay primary Mtb infection in HEU and other high-risk infants are warranted. Clinical Trials Registration NCT02613169.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 815.3-815
Author(s):  
X. Chen ◽  
L. Wu ◽  
X. Wu ◽  
C. N. Luo ◽  
Y. M. Shi

Background:AIDS is a deadly infectious disease caused by the HIV. When HIV infects a host, it may induce production of autoantibodies due to the structural antigen similarity between viral proteins and selfantigens.The molecular mimicry between HIV protein and self-antigens could cause antibody cross-reactions and lead to development of autoimmune disease.Objectives:To explore the clinical value of serum autoantibodies and human leukocyte antigen (HLA-B27) molecular testing in Uygur patients with human immunodeficiency virus (HIV) infection.Methods:A total of 727 HIV-infected Uygur patients who visited Kuche Infectious Diseases Hospital during May 2016 to March 2017 were include in this study. The other 390 healthy people were enrolled as controls. Serum antinuclear antibodies (ANA) and ANA Profile, anti-cyclic citrullinated peptide (CCP) antibody, and HLA-B27 molecule were tested.Results:Among 727 HIV-infected Uygur patients, 317 were males and 410 were females with mean age (35.52±13.44) years old. The mean duration of disease was (6.34±3.05)years. There were 697(95.87%) patients receiving Highly active antiretroviral therapy (HAART) with mean duration of treatment (6.34±3.05)years. Rheumatic manifestations were recorded in 238 (32.74%) HIV-infected Uygur patients, mainly with dry mouth and dry eye (15.41%), alopecia (9.90%), arthralgia (8.94%), ect. Compared with the health controls, positive ANA was more common in HIV infected Uygur patients (33.42%vs.17.43%,P< 0.001) with low titers (ANA titer:1:100). HIV-infected Uygur patients had higher positive anti-u1-RNP antibodies positive rate (1.10%), but lower anti-SSA antibodies positive rate (0.14%) and anti-CCP antibodies positive rate (0.28%). Patients with positive ANA in HAART group were significantly less than that in non-treatment group (38.72%vs.50.00%,P=0.049).Only one female patient was HLA-B27 positive (0.14%), which was significantly lower than that in healthy controls (3.08%) (P<0.001). Also, only one patient was diagnosed with rheumatoid arthritis (RA).Conclusion:Rheumatic manifestations are common in HIV-infected Uygur patients. Several autoantibodies are positive, but the coincidence of rheumatic diseases is rare. It’s noted that patients with Rheumatic manifestations and low titre positive ANA should be considered as a differential diagnosis of HIV infection.Disclosure of Interests:None declared


Sign in / Sign up

Export Citation Format

Share Document