Nutritional Contributions to the CNS Pathophysiology of HIV-1 Infection and Implications for Treatment

Baldewicz, Teri; Brouwers, Pirn; Goodkin, Karl; Kumar, Adarsh; Kumar, Mahendra

doi:10.1017/s1092852900013122

Cited by 8 publications

(5 citation statements)

References 124 publications

(97 reference statements)

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“…Nutritional deficiencies including micronutrients can be a primary causative factor in HIV disease progression, thereby contributing to cognitive dysfunction. 23 The population in this study, however, was mostly observed to be adequately nourished.…”

Section: Resultsmentioning

confidence: 84%

Randomized trial of minocycline in the treatment of HIV-associated cognitive impairment

et al. 2013

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Objective: To evaluate the efficacy and safety of minocycline in the management of HIV-associated cognitive impairment. Methods:We enrolled HIV-positive participants with a CD4 count of 250 to 500 cells/mL in a randomized, double-blind, placebo-controlled study. They received 100 mg of minocycline or matching placebo orally every 12 hours for 24 weeks. Cognitive function was measured using the Uganda Neuropsychological Test Battery Summary Measure (U NP Sum) and the Memorial Sloan-Kettering (MSK) scale. The primary efficacy measure was the 24-week change in an average of 9 standardized U NP Sum z scores.Results: Seventy-three participants were enrolled. Of these, 90% were female, 49% were between the ages 30 and 39 years, and 74% had 6 or more years of education. One participant had MSK score of stage 1 (i.e., mild HIV dementia), and 72 participants had MSK stage 0.5 (i.e., equivocal or subclinical dementia) at the baseline evaluation. The minocycline effect on the 24-week change of the U NP Sum compared with placebo was 0.03 (95% confidence interval 20.51, 0.46; p 5 0.37).

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Section: Resultsmentioning

confidence: 84%

Randomized trial of minocycline in the treatment of HIV-associated cognitive impairment

et al. 2013

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“…The role of other factors including that of low levels of vitamin B6 reported in HIV-1 infection [52,53] may also contribute to a decrease in CSF 5-HT levels, since vitamin B6 is an important cofactor for the activity of 5-hydroxytryptophan decarboxylase, the enzyme used during the last step in 5-HT synthesis.…”

Section: Discussionmentioning

confidence: 99%

Cerebrospinal Fluid 5-Hydroxytryptamine and 5-Hydroxyindoleacetic Acid in HIV-1 Infection

Kumar¹,

Berger²,

Eisdorfer³

et al. 2001

Neuropsychobiology

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Reduced level of serotonin (5-hydroxytryptamine, 5-HT) in humans has been associated with a number of mental health and behavioral problems including depression, aggression, violence, sexual dysfunctions, sleep and eating disorders. Even though among HIV-1-infected individuals, prevalence of mental health and behavioral problems are common, their relationship with central nervous system serotonin functions is not clearly understood. This investigation was carried out to study the status of CSF 5-HT in HIV-1+ subjects (n = 21), in the early stage of infection, and HIV-1– control subjects (n = 24). Samples of CSF were obtained by lumbar puncture and were analyzed for 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA), using high-performance liquid chromatography equipped with electrochemical detector. Levels of CSF 5-HT were significantly lower in the HIV-1+ group compared to the HIV-1– group. There was no significant difference in the CSF 5-HIAA levels between the two groups. In both groups, however, there was a significant correlation between CSF 5-HT and 5-HIAA. In the HIV-1 + group, although CSF 5-HT level was significantly negatively correlated with serostatus, there was no correlation between either CSF 5-HT or 5-HIAA levels and CD4 cell number or any behavioral measures evaluated in this study, including Beck’s Depression Inventory and state/trait anxiety scores. These data suggest that HIV-1 infection affects the CNS 5-HT status with no significant association with measures of depression and anxiety, at least in the early stage of infection.

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“…Inflammatory disorders are characterized by oxidative stress conditions, which lead to low plasma levels of antioxidants, thus also of vitamins. Nutritional imbalances and deficiencies may contribute to neuropsychiatric disturbances and immune dysregulation associated with HIV-1 infection ( 68 ).…”

Section: Vitamin Status Nutrition and Inflammatory Stressmentioning

confidence: 99%

“…Otherwise, more complex dietary interventions might bear a great potential to increase the clinical benefits of HIV patients. Certainly, nutritional and metabolic parameters play an important role in the pathophysiology of HIV infection and might have therapeutic implications ( 13 , 68 ), which is particularly relevant for individuals suffering from severe nutritional deficiencies ( 80 ). For example, in a study cohort of 504 HIV-infected patients undergoing first ART, low protein nutrition was associated with severity of depression ( 35 ).…”

Section: Vitamin Status Nutrition and Inflammatory Stressmentioning

confidence: 99%

Disturbed Amino Acid Metabolism in HIV: Association with Neuropsychiatric Symptoms

et al. 2015

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Blood levels of the amino acid phenylalanine, as well as of the tryptophan breakdown product kynurenine, are found to be elevated in human immunodeficiency virus type 1 (HIV-1)-infected patients. Both essential amino acids, tryptophan and phenylalanine, are important precursor molecules for neurotransmitter biosynthesis. Thus, dysregulated amino acid metabolism may be related to disease-associated neuropsychiatric symptoms, such as development of depression, fatigue, and cognitive impairment. Increased phenylalanine/tyrosine and kynurenine/tryptophan ratios are associated with immune activation in patients with HIV-1 infection and decrease upon effective antiretroviral therapy. Recent large-scale metabolic studies have confirmed the crucial involvement of tryptophan and phenylalanine metabolism in HIV-associated disease. Herein, we summarize the current status of the role of tryptophan and phenylalanine metabolism in HIV disease and discuss how inflammatory stress-associated dysregulation of amino acid metabolism may be part of the pathophysiology of common HIV-associated neuropsychiatric conditions.

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Nutritional Contributions to the CNS Pathophysiology of HIV-1 Infection and Implications for Treatment

Cited by 8 publications

References 124 publications

Randomized trial of minocycline in the treatment of HIV-associated cognitive impairment

Randomized trial of minocycline in the treatment of HIV-associated cognitive impairment

Cerebrospinal Fluid 5-Hydroxytryptamine and 5-Hydroxyindoleacetic Acid in HIV-1 Infection

Disturbed Amino Acid Metabolism in HIV: Association with Neuropsychiatric Symptoms

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