Page last updated: 2024-10-18

kynurenine and Acquired Immune Deficiency Syndrome

kynurenine has been researched along with Acquired Immune Deficiency Syndrome in 14 studies

Kynurenine: A metabolite of the essential amino acid tryptophan metabolized via the tryptophan-kynurenine pathway.
kynurenine : A ketone that is alanine in which one of the methyl hydrogens is substituted by a 2-aminobenzoyl group.

Research Excerpts

ExcerptRelevanceReference
"In these symptoms, AIDS resembles classical pellagra due to dietary deficiency of Trp and niacin."6.38Implications of interferon-induced tryptophan catabolism in cancer, auto-immune diseases and AIDS. ( Borden, EC; Brown, RR; Datta, SP; Malone, DG; Ozaki, Y; Sondel, PM, 1991)
"In participants with intermediate-stage AMD at enrollment in the Longitudinal Study of the Ocular Complications of AIDS (LSOCA) and 2:1 controls matched for age and sex, cryopreserved baseline plasma specimens were assayed for biomarkers of inflammation, including high-sensitivity C-reactive protein (CRP), interleukin (IL)-6, interferon-γ inducible protein (IP)-10, soluble CD14 (sCD14), soluble CD163 (sCD163), kynurenine/tryptophan (KT) ratio, and intestinal fatty acid binding protein (I-FABP)."3.91Association of Age-related Macular Degeneration With Mortality in Patients With Acquired Immunodeficiency Syndrome; Role of Systemic Inflammation. ( Cheu, R; Danis, RP; Hunt, PW; Jabs, DA; Jones, NG; Klatt, NR; Milush, JM; Trang, G; Van Natta, ML, 2019)
"In these symptoms, AIDS resembles classical pellagra due to dietary deficiency of Trp and niacin."2.38Implications of interferon-induced tryptophan catabolism in cancer, auto-immune diseases and AIDS. ( Borden, EC; Brown, RR; Datta, SP; Malone, DG; Ozaki, Y; Sondel, PM, 1991)
"Disease progression was monitored by determination of viral load (VL), CD4(+) cell counts, haemoglobin and urinary/plasma neopterin, tryptophan and kynurenine concentrations."1.35Quality of life and immune activation in patients with HIV-infection. ( Fuchs, D; Kemmler, G; Mumelter, B; Sarcletti, M; Schroecksnadel, K; Weiss, G; Winkler, C; Zangerle, R, 2008)
"Quinolinic acid (QUIN) is a neurotoxic tryptophan metabolite produced by macrophages in response to stimulation with cytokines or infection with HIV-1."1.30Kynurenine pathway inhibition reduces neurotoxicity of HIV-1-infected macrophages. ( Armati, PJ; Brew, BJ; Kerr, SJ; Pemberton, LA; Smythe, G; Tattam, B, 1997)
"CSF quinolinic acid levels were also elevated in all infected macaques, but particularly those with retrovirus-induced encephalitis."1.30Sources of the neurotoxin quinolinic acid in the brain of HIV-1-infected patients and retrovirus-infected macaques. ( Achim, CL; Heyes, MP; Lackner, A; Markey, SP; Saito, K; Wiley, CA, 1998)
"Quinolinic acid (QUIN) is an neurotoxic N-methyl-D-aspartate receptor agonist and an L-tryptophan metabolite of the kynurenine pathway."1.28Inter-relationships between quinolinic acid, neuroactive kynurenines, neopterin and beta 2-microglobulin in cerebrospinal fluid and serum of HIV-1-infected patients. ( Bhalla, RB; Brew, BJ; Der, M; Heyes, MP; Lee, K; Markey, SP; Price, RW; Quearry, BJ; Saito, K, 1992)

Research

Studies (14)

TimeframeStudies, this research(%)All Research%
pre-19901 (7.14)18.7374
1990's7 (50.00)18.2507
2000's2 (14.29)29.6817
2010's4 (28.57)24.3611
2020's0 (0.00)2.80

Authors

AuthorsStudies
Jabs, DA1
Van Natta, ML1
Trang, G1
Jones, NG1
Milush, JM1
Cheu, R1
Klatt, NR1
Danis, RP1
Hunt, PW1
Nzowa, LK1
Teponno, RB1
Tapondjou, LA1
Verotta, L1
Liao, Z1
Graham, D2
Zink, MC2
Barboni, L1
Sacktor, N1
Miyahara, S1
Evans, S1
Schifitto, G1
Cohen, B1
Haughey, N1
Drewes, JL1
Anderson, C1
Nath, A1
Pardo, CA1
McCarthy, S1
Hosey, L1
Clifford, D1
Bipath, P1
Levay, PF1
Viljoen, M1
Zangerle, R2
Widner, B1
Quirchmair, G1
Neurauter, G1
Sarcletti, M2
Fuchs, D4
Schroecksnadel, K1
Winkler, C1
Mumelter, B1
Weiss, G1
Kemmler, G1
Kerr, SJ1
Armati, PJ1
Pemberton, LA1
Smythe, G1
Tattam, B1
Brew, BJ2
Huengsberg, M1
Winer, JB1
Gompels, M1
Round, R1
Ross, J1
Shahmanesh, M1
Heyes, MP3
Saito, K2
Lackner, A1
Wiley, CA1
Achim, CL1
Markey, SP2
Quearry, BJ2
Price, RW1
Lee, K1
Bhalla, RB1
Der, M1
Brown, RR1
Ozaki, Y1
Datta, SP1
Borden, EC1
Sondel, PM1
Malone, DG1
Möller, AA1
Reibnegger, G2
Stöckle, E1
Werner, ER2
Wachter, H2
Hausen, A1
Jaeger, H1
Werner-Felmayer, G1
Dierich, MP1

Clinical Trials (1)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
Phase II, Randomized, Placebo-Controlled, Double-Blind Study of Minocycline in the Treatment of HIV-Associated Cognitive Impairment[NCT00361257]Phase 2107 participants (Actual)Interventional2007-03-31Terminated (stopped due to This study was terminated early due to futility.)
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

Change in Cognitive Gross Motor Function Domain Z-Score

The cognitive gross motor function is a age and education adjusted z score of Timed Gait (TIG). The outcome is the 24 week change of cognitive gross motor function domain z-scores (week 24-baseline). (NCT00361257)
Timeframe: At baseline and week 24

Interventionz-score (Mean)
Minocycline0.22
Matching Placebo0.08

Change in Cognitive Performance Compared to Baseline

"Th cognitive performance is measured by NPZ-8. NPZ-8 is defined as the average of age and education adjusted z-scores of eight neuropsychological tests subcomponents in the neuropsychological test battery. These eight tests are:~Grooved Pegboard Dominant Hand (GPD)~Grooved Pegboard Non-dominant hand (GPN)~Choice Reaction Time (CRT)~Sequential Reaction Time (QRT)~Timed Gait (TIG)~Trail Making Part A (TMA)~Trail Making Part B (TMB)~Symbol Digit (SYD) The primary outcome is NPZ-8 score at week24 - NPZ-8 score at baseline." (NCT00361257)
Timeframe: At baseline and week 24

Interventionz-score (Mean)
Minocycline0.12
Matching Placebo0.17

Change in Fine Motor Function Domain Z-Score

The fine motor function domain score is an average of age, sex, education, and African-American ethnicity adjusted z scores of Grooved Pegboard Dominant Hand (GPD) and Grooved Pegboard Non-dominant hand (GPN). The outcome is a 24 week change of the fine motor function domain z-score (week 24-baseline). (NCT00361257)
Timeframe: At baseline and week 24

Interventionz-score (Mean)
Minocycline0.27
Matching Placebo0.05

Change in Fine Motor/Nonverbal Function Domain Z-Score

The fine motor/nonverbal function domain score is a age and education adjusted z score of Symbol Digit Test (SYD) The outcome is the 24 change of fine motor/nonverbal function domain z-score (week 24-baseline). (NCT00361257)
Timeframe: At baseline and week 24

Interventionz-score (Mean)
Minocycline-0.15
Matching Placebo-0.07

Change in Frontal Systems Function Domain Z-Score

The frontal systems function domain score is the average of age and education adjusted z scores of Stroop Color Interference Test (CTP) and interference task (STP). The outcome is the 24 week change of frontal systems function domain z-score (week 24-baseline). (NCT00361257)
Timeframe: At baseline and week 24

Interventionz-score (Mean)
Minocycline-0.04
Matching Placebo0.21

Change in Global Deficit Z-Score (GDS)

GDS on the test battery is the simple average of all 14 individual deficit scores in the test battery, including Time Gait, Grooved Pegboard Test for the dominant and non-dominant hands, Trail Making Test parts A and B, Symbol Digit Test, simple and sequential reaction time - CalCAP, Hopkins Verbal Learning Test (Revised)- Learning, Delayed Recall and Recognition trials, and Stroop Color Interference Test-color, word, and interference tasks. The outcome is the 24 week change of GDS Z-score (24 week-baseline). (NCT00361257)
Timeframe: At baseline and week 24

Interventionz-score (Mean)
Minocycline0.11
Matching Placebo0.09

Change in Information Processing Function Domain Z-Score

The information processing function domain score is the average of age and education adjusted z scores of simple and sequential reaction time - CalCAP. The outcome is the 24 week change of information processing function domain z-scores (week 24-baseline). (NCT00361257)
Timeframe: At baseline and week 24

Interventionz-score (Mean)
Minocycline0.14
Matching Placebo0.20

Change in Psychomotor Function Domain Z-Score

The psychomotor function domain score us the average of age, sex, education, and African-American ethnicity adjusted z scores of Trail Making Part A (TMA) and Trail Making Part B (TMB). The outcome is the 24 week change of psychomotor function domain z-scores (week24-baseline). (NCT00361257)
Timeframe: At baseline and week 24

Interventionz-score (Mean)
Minocycline0.07
Matching Placebo0.15

Change in Verbal Memory Domain Z-Score

The verbal memory domain score is the average of age and education adjusted z scores of Hopkins Verbal Learning Test- Revised, Learning and Delayed Recall. The outcome is the 24 week change of verbal memory domain z-scores (week 24-baseline). (NCT00361257)
Timeframe: At baseline and week 24

Interventionz-score (Mean)
Minocycline0.18
Matching Placebo0.02

Changes in Alternate Frontal Systems Z-Score

The alternate frontal systems was defined as a mean of age and education adjusted z score of Interference task, and age, sex, education, and African-American ethnicity adjusted z score of Trail Making Part B. The outcome was the 24 week change in alternate frontal systems z-score (week 24-baseline). (NCT00361257)
Timeframe: At baseline and week 24

Interventionz-score (Mean)
Minocycline0.03
Matching Placebo-0.07

Changes in Alternate Psychomotor Function Z-Score

The alternate psychomotor function is defined as the mean of age, sex, education, and African-American ethnicity adjusted z scores of Trail Making Part A (TMA), and age and education adjusted z score of Symbol Digit (SYD). The outcome is the 24 week change in alternate psychomotor function z-score (week 24-baseline). (NCT00361257)
Timeframe: At baseline and week 24

Interventionz-score (Mean)
Minocycline-0.03
Matching Placebo0.05

Changes in Alternate Verbal Memory Z-Score

The alternate verbal memory was defined as a mean of age and education adjusted z score of trials 1 to 3 and delayed recall tests. The outcome is the 24 week change in alternate verbal memory z-score (week 24-baseline). (NCT00361257)
Timeframe: At baseline and week 24

Interventionz-score (Mean)
Minocycline0.18
Matching Placebo0.02

Changes in Cluster of Differentiation 4 (CD4) Cell Counts (24 Weeks)

The outcome was the 24 week change in CD4 cell count (week 24-baseline). (NCT00361257)
Timeframe: At baseline and weeks 24

Interventioncells/mm^3 (Mean)
Minocycline24.10
Matching Placebo8.24

Changes in Cluster of Differentiation 8 (CD8) Cell Counts (24 Weeks)

The outcome was the 24 week change of CD8 cell counts (week 24-baseline). (NCT00361257)
Timeframe: At baseline and week 24

Interventioncells/mm^3 (Mean)
Minocycline43.90
Matching Placebo0.00

Changes in Markers of Oxidative Stress (Unit = Pixels/mm2 Only)

Protein marker of oxidative stress (Neurofilament heavy polypeptide). The outcome is the 24 week change (week 24-baseline). (NCT00361257)
Timeframe: At pre-entry and Week 24

InterventionPixels/mm^2 (Median)
Arm 1: Minocycline-59.3
Arm 2: Matching Placebo-3.04

Changes in Medication Management Test (Modified)

The medication management test (modified) is designed to assess participants' medication management ability and their own medications and management. It's the number of how many times participants correctly answered 16 questions. The score ranges between 0 and 16, and higher score indicates better medication management. (NCT00361257)
Timeframe: At baseline and weeks 24

Interventionscores on a scale (Mean)
Minocycline0.16
Matching Placebo0.48

Change in Investigator's Clinical Global Impression Score (ICGIS)

"Clinicians were asked to rate their overall impression about the clinical improvement or worsening of his/her study participants. They can choose from the following 7 levels: (0) No Change, (1) Mild Improvement, (2) Moderate Improvement, (3) Marked Improvement, (4) Mild Worsening, (5) Moderate Worsening, and (6) Marked Worsening.~For the analysis, we simplified the outcome into the following 3 levels: (0) worsened, (1) No Change, and (2) Improved." (NCT00361257)
Timeframe: At week 24

,
Interventionparticipants (Number)
WorsenedNo ChangeImproved
Matching Placebo23112
Minocycline4289

Change in Karnofsky Performance Score

"The original Karnofsky performance score is 11 level score which ranges between 0 to 100. The score 100 means normal and 0 means death; therefore, higher score means higher ability to perform daily tasks.~For the analysis, a new dichotomous variable (no change/worse vs. better at 24 weeks compared to baseline) was created." (NCT00361257)
Timeframe: At baseline and week 24

,
Interventionparticipants (Number)
No Change/WorseBetter
Matching Placebo423
Minocycline336

Change of HIV Plasma RiboNucleic Acid (RNA) Viral Load

The original scale of HIV RNA viral load is between 30 copies/mL to infinitive. The minimum score of 30 is the lowest detectable value. The summary table categorized this continuous value to a dichotomous variable (<30 copies/mL and >= 30 copies/mL). (NCT00361257)
Timeframe: At baseline and week 24

,
Interventionparticipants (Number)
>= 30 copies/mL at base, >= 30 at week 24>= 30 copies/mL at base, < 30 at week 24< 30 copies/mL at base, >= 30 at week 24< 30 copies/mL at base, < 30 at week 24
Matching Placebo02019
Minocycline10217

Changes in Instrumental Activities of Daily Living Questionnaire

The Instrumental Activities of Daily Living (IADL) questionnaire is designed to learn more about how subjects are able to perform common tasks. There are 16 common tasks. For each task, if the score at the time of evaluation is worse than the best in the past, an indicator of 1 is given. Otherwise, the indicator is 0. The overall IADL score is a sum of 16 indicators divided by 16; therefore, the range is between 0 and 1 and the lower score is better. The 24-week change of IADL score was changed into a categorical variable (no change/worse vs. better) at week 24 compare to baseline. (NCT00361257)
Timeframe: At baseline and week 24

,
Interventionparticipants (Number)
No Change/WorseBetter
Matching Placebo3211
Minocycline3012

Changes in Markers of Oxidative Stress and Immune Activation (Unit=pg/mL Only)

Protein markers of oxidative stress (Protein carbonyls) and markers of immune activation (TNF-a, IL-6,CXCL8, Hepatocyte growth factor, Osteopontin, sFAS, sFAS ligand, and CXCL12). For all markers, the outcome is the 24 week change (week 24-baseline). (NCT00361257)
Timeframe: At pre-entry and Week 24

,
Interventionpg/mL (Median)
Protein carbonyls (pg/ml)TNF-α (pg/mL)IL-6 (pg/mL)CXCL8 (pg/mL)Hepatocyte growth factor (pg/mL)Osteopontin (pg/mL)sFAS (pg/mL)sFAS ligand (pg/mL)CXCL12 (pg/mL)
Arm 1: Minocycline4.00.04-0.290.3416.09-5208.940.68-0.27204.39
Arm 2: Matching Placebo13.20.140.95-6.1390.48673.55134.10.111,071.84

Changes in Neurotransmitter Levels (Unit = uM Only)

Neurotransmitter levels (Glutamate, Tryptophan, Anthranilic Acid, Quinolinic Acid, Kynurenin, and 3-Hydroxykynurenine). The outcome is the 24 week change (week 24-baseline). (NCT00361257)
Timeframe: At pre-entry and Week 24

,
InterventionuM (Median)
Glutamate (uM)Tryptophan (uM)Anthranilic Acid (uM)Quinolinic Acid (uM)Kynurenin (uM)3-Hydroxykynurenine (uM)
Arm 1: Minocycline5.09-0.210.0-0.556.85-4.09
Arm 2: Matching Placebo-1.080.070.00.06.97-0.83

Changes in Protein Markers of Oxidative Stress (Unit = Counts Per Second Only)

Protein marker of oxidative stress (Ceramides, Monohexosylceramides, Dihydro Glycosyl Galceramides, and Dihexosylceramides). For all markers, the outcome is the 24 week change (week 24-baseline). (NCT00361257)
Timeframe: At pre-entry and Week 24

,
Interventioncounts per second (Median)
Ceramides (counts per second)Monohexosylceramides (counts per second)Dihydro Glycosyl Galceramides (counts per second)Dihexosylceramides (counts per second)
Arm 1: Minocycline0.00070.00130.02010.0005
Arm 2: Matching Placebo-0.0051-0.0066-0.0048-0.0043

Number of Participants With Grade 2 or Higher Toxicity and/or Signs and Symptoms

Grade or higher means that adverse events were moderate, severe, or life-threatening, or death. Grade 2 or higher adverse events are lised in the Adverse Event section. (NCT00361257)
Timeframe: Throughout study up to week 48

,
Interventionparticipants with an event (Number)
0 - 4 weeks4.01 - 12 weeks12.01 - 24 weeks24.01 - 48 weeks
Matching Placebo32312
Minocycline29521

Reviews

1 review available for kynurenine and Acquired Immune Deficiency Syndrome

ArticleYear
Implications of interferon-induced tryptophan catabolism in cancer, auto-immune diseases and AIDS.
    Advances in experimental medicine and biology, 1991, Volume: 294

    Topics: Acquired Immunodeficiency Syndrome; Autoimmune Diseases; Enzyme Induction; Female; Humans; Indoleami

1991

Trials

1 trial available for kynurenine and Acquired Immune Deficiency Syndrome

ArticleYear
Impact of minocycline on cerebrospinal fluid markers of oxidative stress, neuronal injury, and inflammation in HIV-seropositive individuals with cognitive impairment.
    Journal of neurovirology, 2014, Volume: 20, Issue:6

    Topics: Acquired Immunodeficiency Syndrome; Administration, Oral; Adult; AIDS Dementia Complex; Anti-HIV Age

2014

Other Studies

12 other studies available for kynurenine and Acquired Immune Deficiency Syndrome

ArticleYear
Association of Age-related Macular Degeneration With Mortality in Patients With Acquired Immunodeficiency Syndrome; Role of Systemic Inflammation.
    American journal of ophthalmology, 2019, Volume: 199

    Topics: Acquired Immunodeficiency Syndrome; Adult; Antigens, CD; Biomarkers; C-Reactive Protein; Case-Contro

2019
Two new tryptophan derivatives from the seed kernels of Entada rheedei: effects on cell viability and HIV infectivity.
    Fitoterapia, 2013, Volume: 87

    Topics: Acquired Immunodeficiency Syndrome; Brain; Cell Line; Cell Survival; Dopamine; Fabaceae; Glutamic Ac

2013
The kynurenine pathway activities in a sub-Saharan HIV/AIDS population.
    BMC infectious diseases, 2015, Aug-19, Volume: 15

    Topics: Acquired Immunodeficiency Syndrome; Adult; Africa South of the Sahara; Antiretroviral Therapy, Highl

2015
Effective antiretroviral therapy reduces degradation of tryptophan in patients with HIV-1 infection.
    Clinical immunology (Orlando, Fla.), 2002, Volume: 104, Issue:3

    Topics: Acquired Immunodeficiency Syndrome; Adult; Anti-HIV Agents; CD4 Lymphocyte Count; Drug Therapy, Comb

2002
Quality of life and immune activation in patients with HIV-infection.
    Brain, behavior, and immunity, 2008, Volume: 22, Issue:6

    Topics: Acquired Immunodeficiency Syndrome; Adult; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; Depress

2008
Kynurenine pathway inhibition reduces neurotoxicity of HIV-1-infected macrophages.
    Neurology, 1997, Volume: 49, Issue:6

    Topics: Acquired Immunodeficiency Syndrome; Brain; Cell Aggregation; Cells, Cultured; Coloring Agents; Fetus

1997
Serum kynurenine-to-tryptophan ratio increases with progressive disease in HIV-infected patients.
    Clinical chemistry, 1998, Volume: 44, Issue:4

    Topics: Acquired Immunodeficiency Syndrome; Adult; Aged; AIDS Dementia Complex; CD4 Lymphocyte Count; Female

1998
Sources of the neurotoxin quinolinic acid in the brain of HIV-1-infected patients and retrovirus-infected macaques.
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 1998, Volume: 12, Issue:10

    Topics: Acquired Immunodeficiency Syndrome; Animals; Brain; Central Nervous System; Cerebral Cortex; HIV-1;

1998
Inter-relationships between quinolinic acid, neuroactive kynurenines, neopterin and beta 2-microglobulin in cerebrospinal fluid and serum of HIV-1-infected patients.
    Journal of neuroimmunology, 1992, Volume: 40, Issue:1

    Topics: Acquired Immunodeficiency Syndrome; AIDS Dementia Complex; beta 2-Microglobulin; Biopterins; Blood-B

1992
Decreased serum tryptophan in patients with HIV-1 infection correlates with increased serum neopterin and with neurologic/psychiatric symptoms.
    Journal of acquired immune deficiency syndromes, 1990, Volume: 3, Issue:9

    Topics: Acquired Immunodeficiency Syndrome; Adult; Biopterins; Dementia; Humans; Kynurenine; Male; Middle Ag

1990
Quantification of kynurenic acid in cerebrospinal fluid: effects of systemic and central L-kynurenine administration.
    Journal of chromatography, 1990, Aug-24, Volume: 530, Issue:1

    Topics: Acquired Immunodeficiency Syndrome; Animals; Chromatography, High Pressure Liquid; Cisterna Magna; H

1990
Tryptophan degradation in patients infected by human immunodeficiency virus.
    Biological chemistry Hoppe-Seyler, 1988, Volume: 369, Issue:5

    Topics: Acquired Immunodeficiency Syndrome; Adult; Biopterins; Humans; Kynurenine; Male; Neopterin; Referenc

1988