scholarly journals A Randomized Controlled Trial of Isoniazid to Prevent Mycobacterium tuberculosis Infection in Kenyan Human Immunodeficiency Virus–Exposed Uninfected Infants

2020 ◽  
Author(s):  
Sylvia M LaCourse ◽  
Barbra A Richardson ◽  
John Kinuthia ◽  
A J Warr ◽  
Elizabeth Maleche-Obimbo ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Mycobacterium Tuberculosis ◽  
High Risk ◽  
Adverse Events ◽  
Controlled Trial ◽  
Preventive Therapy ◽  
Infection Prevalence ◽  
Mycobacterium Tuberculosis Infection ◽  
Immunodeficiency Virus ◽  
Exposed Uninfected

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.

scholarly journals Vesatolimod, a Toll-like Receptor 7 Agonist, Induces Immune Activation in Virally Suppressed Adults Living With Human Immunodeficiency Virus–1

2020 ◽  
Author(s):  
Sharon A Riddler ◽  
Michael Para ◽  
Constance A Benson ◽  
Anthony Mills ◽  
Moti Ramgopal ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Adverse Events ◽  
Controlled Trial ◽  
Study Drug ◽  
Primary Study ◽  
Drug Discontinuation ◽  
People Living With Hiv ◽  
Toll Like Receptor ◽  
Immunodeficiency Virus ◽  
Hiv 1

Abstract Background Treatment with vesatolimod, an investigational, oral, toll-like receptor 7 (TLR7) agonist, leads to sustained viral remission in some non-human primates when combined with anti-envelope antibodies or therapeutic vaccines. We report results of a Phase Ib study evaluating safety, pharmacokinetics, and pharmacodynamics of vesatolimod in adults living with human immunodeficiency virus (HIV)–1. Methods In this double-blind, multicenter, placebo-controlled trial, participants on antiretroviral therapy with screening plasma HIV-1 RNA levels <50 copies/mL were randomized (6:2) to receive 6–10 doses of vesatolimod (1–12 mg) or matching placebo orally every other week in sequential dose-escalation cohorts. The primary study objectives included establishing the safety and virologic effects of vesatolimod (change from baseline in plasma HIV-1 RNA). Pharmacokinetics and pharmacodynamic/immunologic activity were assessed as secondary objectives. Results A total of 48 individuals were randomly assigned to vesatolimod (n = 36) or placebo (n = 12). Vesatolimod was generally well tolerated, with no study drug–related serious adverse events or adverse events leading to study drug discontinuation. There were no statistically significant changes from baseline in plasma HIV-1 RNA in the vesatolimod groups, compared to placebo. Vesatolimod plasma exposures increased dose proportionally; consistent responses in cytokines, interferon-stimulated gene expression, and lymphocyte activation were observed with increasing dose levels above 4 mg. Peak elevations 24 hours after receipt of a 6 mg dose were >3.9-fold higher for interferon gamma-induced protein 10 (IP-10), interleukin-1 receptor antagonist (IL-1RA), interferon–inducible T-cell alpha chemoattractant (ITAC) when compared to baseline values. Conclusions Vesatolimod was well tolerated at doses ranging from 1 to 12 mg. Immune stimulation was observed at doses above 4 mg, providing rationale for future combination trials in people living with HIV. Clinical Trials Registration NCT02858401.

scholarly journals Antigens of Mycobacterium tuberculosis Recognized by Antibodies during Incipient, Subclinical Tuberculosis

2005 ◽  
Vol 12 (2) ◽  
pp. 354-358 ◽  
Author(s):  
Krishna K. Singh ◽  
Yuxin Dong ◽  
John T. Belisle ◽  
Jeffrey Harder ◽  
Vijay K. Arora ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Mycobacterium Tuberculosis ◽  
High Risk ◽  
Culture Filtrate ◽  
Diagnostic Tests ◽  
Malate Synthase ◽  
Hiv Positive ◽  
Serum Samples ◽  
Immunodeficiency Virus ◽  
Culture Filtrate Proteins

ABSTRACT Serum samples obtained from human immunodeficiency virus (HIV)-infected tuberculosis (TB) patients months prior to clinical TB were used to delineate the profile of Mycobacterium tuberculosis culture filtrate proteins recognized during subclinical TB. A subset of ∼12 antigens was recognized by antibodies in these serum samples. Antibodies to two of these antigens (81 [88]-kDa malate synthase [GlcB] and MPT51) were present in serum samples obtained during incipient subclinical TB in 19 (∼90%) of the 21 HIV-infected TB patients tested. These antigens will be useful for devising diagnostic tests that can identify HIV-positive individuals who are at a high risk for developing clinical TB.

scholarly journals SAT0078 SAFETY OF LOW DOSE METHOTREXATE (MTX) IN HUMAN IMMUNODEFICIENCY VIRUS (HIV) INFECTION

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 974.2-974
Author(s):  
A. Gunay ◽  
A. Davidson ◽  
I. Colmegna ◽  
D. Lacaille ◽  
H. Loewen ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Adverse Events ◽  
Low Dose ◽  
Opportunistic Infections ◽  
Case Reports ◽  
Cross Sectional Study ◽  
Study Quality ◽  
Sectional Study ◽  
Cross Sectional ◽  
Immunodeficiency Virus

Background:Increased awareness of the efficacy of MTX in rheumatic disease is leading to more MTX use in patients from HIV endemic areas. While HIV related immunosuppression may contribute to improvement of some rheumatic diseases, immune reconstitution from highly active antiretroviral therapy (HAART) may lead to exacerbation or presentation of autoimmune disorders for which MTX therapy may be warranted. Most management guidelines for rheumatic disease do not address MTX use in the context of HIV.Objectives:To systematically review the published literature on the safety of using MTX ≤30 mg per week in HIV.Methods:We searched CINAHL, Embase, Global, MEDLINE and World of Science databases (Jan 1990 to May 2018) for terms including ‘methotrexate’ and ‘human immunodeficiency virus’. We also searched citations from review articles. Titles, abstracts or full manuscripts were screened independently by 2 reviewers to identify studies reporting HIV in patients taking MTX. Study quality was assessed using the McGill Mixed Methods Appraisal Tool (MMAT). Data was extracted on MTX and HIV adverse events (MTX toxicity, HIV viral load, CD4 count). Descriptive summaries are presented for studies providing outcomes in patients taking MTX ≤30 mg per week.Results:After removing duplicates and studies not meeting criteria or not providing sufficient information, 42 of the 2714 identified reports were included (1 clinical trial, 2 cohort, 1 cross-sectional study, 38 case reports/case series). Most reports (81%) originated from USA or Europe. Study quality was generally good with most studies fulfilling 50-100% of MMAT criteria. The randomized controlled trial (USA) assessing MTX on atherosclerotic disease in HIV showed that adverse events were more common in MTX versus placebo (12.8% vs 5.6%, p non-inferiority <0.05) and included infection, transient CD4 and CD8 drop, pulmonary toxicity, and death (1 attributed to MTX/HIV, 1 unrelated). One cohort study (South Africa) reported 43 RA patients on MTX who acquired HIV. In this cohort, RA generally improved despite only 5 individuals continuing MTX. No data on MTX adverse event rates was reported. One cohort study (USA) reported 13 HIV patients with myositis. One received MTX (with other immunosuppression) without MTX adverse effects but died due to AIDS. A cross-sectional study (France) of 43 HIV pts with autoimmune disease reported one patient on MTX (and other immunosuppression) developed an adverse event (cytopenia) compared to 5/33 patients not on MTX (cytopenia). The 38 case reports/series described 54 individuals with HIV receiving MTX. Of these studies, 27 (describing 42 subjects) reported on MTX adverse events and 35 (describing 46 subjects) reported on HIV adverse events. MTX adverse events developed in 29 subjects (hematologic 13, renal/hepatic 1, opportunistic infections 10, other events 2). HIV adverse events were noted in 23 subjects (Kaposi’s sarcoma 4, CD4 decrease 16, HIV viral titer increase 4). Five deaths were reported (2 infection, 1 infection and wasting, 2 HIV related deaths). Most subjects also received corticosteroids or other immunosuppressants including biologics.Conclusion:There remains limited data on the safety of low dose MTX in HIV. Surveillance for HIV is warranted for individuals on MTX who are at risk for acquiring HIV. Caution and careful monitoring for MTX toxicity, opportunistic infections and HIV state is suggested if MTX is used in the setting of HIV particularly if combined with other immunosuppression.References:[1] Clin Infectious Disease 2019:68[2] J Rheumatology 2014:41[3] Arthritis and Rheumatism 2003:49[4] Medicine 2017:96Acknowledgments :Funding from International League Against RheumatismMcGill University Global Health Scholar AwardsDisclosure of Interests:Alize Gunay: None declared, Anna Davidson: None declared, Ines Colmegna: None declared, Diane Lacaille: None declared, Hal Loewen: None declared, Michele Meltzer: None declared, Yewondwossen Mengistu: None declared, Rosie Scuccimarri: None declared, Zenebe Yirsaw: None declared, Sasha Bernatsky: None declared, Carol Hitchon Grant/research support from: UCB Canada; Pfizer Canada

Multidrug Resistant Mycobacterium tuberculosis in Patients with Human Immunodeficiency Virus Infection

CHEST Journal ◽  
1992 ◽  
Vol 102 (3) ◽  
pp. 797-801 ◽  
Author(s):  
Christopher P. Busillo ◽  
Klaus-Dieter Lessnou ◽  
Veraaf Sanjana ◽  
Sarantos Soumakis ◽  
Morton Davidson ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Mycobacterium Tuberculosis ◽  
Virus Infection ◽  
Human Immunodeficiency Virus Infection ◽  
Multidrug Resistant ◽  
Immunodeficiency Virus
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