|Year : 2016 | Volume
| Issue : 4 | Page : 157-161
Serum pyridoxine levels in HIV-positive patients and its association with tuberculosis and neuropsychiatric manifestations
MR Prabha Adhikari1, Sahana Devadasa Acharya2, John T Ramapuram1, Satish B Rao1, Kiran Vadapalli1, Mukta N Chowta2, Sheetal D Ullal2
1 Department of Medicine, Kasturba Medical College, Mangalore, Manipal University, Karnataka, India
2 Department of Pharmacology, Kasturba Medical College, Mangalore, Manipal University, Karnataka, India
|Date of Submission||14-Jul-2016|
|Date of Acceptance||12-Sep-2016|
|Date of Web Publication||7-Oct-2016|
Sahana Devadasa Acharya
Department of Pharmacology, Kasturba Medical College, Light House Hill Road, Hampankatta, Mangalore - 575 001, Karnataka
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Studies have shown the prevalence of micronutrient insufficiency in HIV patients. Decreased plasma levels of pyridoxine, Vitamins B12, A, and E, and zinc have been correlated with significant alterations in immune response and cognitive functions. Serum pyridoxine levels in different subgroup of HIV patients are not well studied.
Objective: To study the proportion of pyridoxine deficiency in different subgroups of HIV-positive patients (HIV with tuberculosis - Group I, HIV with neuropsychiatric manifestations - Group II, and HIV-positive patients without neuropsychiatric symptoms or tuberculosis - Group III) and the comparison of mini mental state examination (MMSE) score, Hamilton depression rating scale (HAM-D), and Hamilton anxiety rating scale (HAM-A) in them.
Methodology: One hundred and fifty HIV patients were divided into three groups. MMSE, HAM-D, HAM-A, hemoglobin levels, pyridoxine levels, waist-hip ratio, and body mass index were noted.
Results: The proportion of patients with pyridoxine deficiency was 18.8% in Group I and 28.3% in Group II. The percentage of pyridoxine deficiency between Group II and Group III significantly differ (P = 0.048). Patients in Group II showed an association with abnormal neuropsychiatric assessment using MMSE/HAM-D/HAM-A (χ2 = 7.843; P = 0.005). There was a significant correlation between CD4 count and pyridoxine in Group I (r = 0.391, P = 0.006) only.
Interpretation and Conclusions: Increased proportion of pyridoxine deficiency is seen in individuals with HIV. Proportion of pyridoxine deficiency is also higher in HIV patients with neuropsychiatric manifestations. HIV patients with neuropsychiatric symptoms and tuberculosis have a low CD4 count and pyridoxine levels as compared to HIV-positive patients without neuropsychiatric symptoms or tuberculosis.
Keywords: Anxiety, CD4 lymphocyte count, depression, HIV infection, pyridoxine, tuberculosis, Vitamin B6 deficiency
|How to cite this article:|
Prabha Adhikari M R, Acharya SD, Ramapuram JT, Rao SB, Vadapalli K, Chowta MN, Ullal SD. Serum pyridoxine levels in HIV-positive patients and its association with tuberculosis and neuropsychiatric manifestations. Int J Nutr Pharmacol Neurol Dis 2016;6:157-61
|How to cite this URL:|
Prabha Adhikari M R, Acharya SD, Ramapuram JT, Rao SB, Vadapalli K, Chowta MN, Ullal SD. Serum pyridoxine levels in HIV-positive patients and its association with tuberculosis and neuropsychiatric manifestations. Int J Nutr Pharmacol Neurol Dis [serial online] 2016 [cited 2019 Oct 23];6:157-61. Available from: http://www.ijnpnd.com/text.asp?2016/6/4/157/191678
| Introduction|| |
Insufficiencies of micronutrients are common in those infected with HIV. This is due to malabsorption, abnormal metabolism, infection, and change in gastrointestinal (GI) barrier function. Several nutrient deficiencies occur quite early during HIV infection. , Decreased plasma levels of Vitamin B6, B12, A, and E and zinc have been correlated with significant alterations in immune response and cognitive functions. , Many studies have documented the role of micronutrient insufficiencies in HIV-infected individuals with the quicker progression of disease ,,,,,,, and raise the possibility that micronutrient supplementation might increase the period of symptom-free survival. HIV-positive patients appear to require an intake of these nutrients in a higher range of recommended dietary allowances when compared to normal individuals. 
Prevalence of pyridoxine deficiency has been reported to be about 53% among HIV-infected individuals in CDC Stage III.  Pyridoxine deficiency is associated with neuropsychiatric manifestations and depressed immune function, including cell-mediated immunity.
Hence, we decided to study the proportion of pyridoxine deficiency in different subgroups of HIV positive patients (HIV with TB, HIV with neuropsychiatric manifestation, and HIV alone), its association with each of these subgroups and the comparison of mini mental state examination (MMSE) score, Hamilton depression rating scale (HAM-D), and Hamilton anxiety rating scale (HAM-A) in these subgroups of HIV-positive patients.
| Methodology|| |
The study was conducted in Kasturba Medical College, Mangalore, a tertiary care hospital with an Infectious Diseases Cell with a database of around 2000 HIV-positive patients, out of which more than 500 are on regular follow-up during the year 2008-2012. This work was conducted in compliance with the Institutional Ethics Committee requirements; informed consent regulations and ICH/GCP guidelines. This cross-sectional study included 150 participants, distributed equally into three groups, after obtaining written informed consent:
HIV-positive patients with coexistent tuberculous infection.
HIV-positive patients with neuropsychiatric symptoms.
HIV-positive patients without neuropsychiatric symptoms or tuberculosis.
Diagnosis of HIV infection was made by two HIV ELISA tests and a mono spot test using three different antigens (or) three mono spot tests positive using three different antigens by Voluntary Counseling and Testing Centre established by the National AIDS Control Organisation, India. 
Coexistent tuberculosis was confirmed by any one of the following: sputum analysis, radiological evidence, molecular diagnosis of extrapulmonary tuberculosis by polymerase chain reaction positivity for tubercular antigen, Mantoux positive >5 mm in patients having CD4 count <200 with clinical symptoms, suggestive of tuberculosis. Absolute CD4 count was done at the time of enrollment by flow cytometry, and its normal reference range was 380-1200 cells/μL. Vitamin B6 estimation was done by high-performance liquid chromatography for all patients in all groups (reference taken for this study was 5-30 ng/mL). A detailed clinical examination was performed which included neurological assessment using MMSE, HAM-D, and HAM-A. A detailed nutritional assessment for anemia, vitamin deficiencies, and waist-hip ratio was performed.
Analysis of data was done using statistical package SPSS 11.0 version (SPSS Inc., Chicago, IL). All the continuous variables were expressed as mean ± standard deviation or median. Proportion of pyridoxine deficiency was expressed as percentage of the particular group. Chi-square test was done to analyze the association between pyridoxine deficiency and the different groups of HIV patients and the neuropsychiatric manifestations. P < 0.05 was considered statistically significant.
| Results|| |
In this study, a total of 150 patients were enrolled. The three groups (I, II, III) consisted of a total of 150 HIV-positive participants with fifty in each group. The demographic features and details of other parameters for all participants are summarized in [Table 1].
The mean age of Groups I, II, and III was 36.28 ± 5.93, 39.22 ± 9.02, and 38.57 ± 8.84 years, respectively. The ratio of male and female patients among the groups was 40:10, 35:15, and 33:17, respectively [Table 2]. The body mass index (BMI) of Groups I-III (in kg/m 2 ) was 17.42 ± 2.84, 17.46 ± 2.99, and 18.82 ± 3.17, respectively. Among the three groups, the BMI was more in Group III and least in Group I. The mean waist circumferences in centimeter of Groups I-III were 69.93 ± 7.84, 68.71 ± 9.84, and 72.61 ± 10.97, respectively. Group III had a greater mean waist circumference of 72.61 compared to the rest of HIV patients. The mean hemoglobin of Groups I, II, and III was 9.86 ± 2.34, 9.81 ± 2.69, and 11.65 ± 2.18, respectively. Mean hemoglobin values were significantly lower in Group I and II compared to Group III (P = 0.001).
The median (interquartile range) serum pyridoxine levels in Groups I, II, III were 8.23 (6.14, 12.06); 8.56 (4.18, 12.82); and 11.13 (8.04, 14.01) ng/mL, respectively [Table 2]. The median pyridoxine level was lowest in Group I, but there was no statistically significant difference between the groups. The proportion of patients with Vitamin B6 deficiency in the Group I was 18.8%, Group II was 28.3%, and Group III was 10%. The proportion of patients with Vitamin B6 deficiency was higher in HIV patients with neuropsychiatric symptoms than any other HIV group. The percentage of B6 deficiency between Group II and Group III significantly differed (P = 0.048). There was no significant difference in proportion of B6 deficiency between the other groups. There was no association between pyridoxine deficiency and HIV patients with tuberculosis, but there was an association between pyridoxine deficiency and HIV patients with neuropsychiatric manifestation (χ2 = 4.013; P = 0.045).
The mean MMSE scores in Groups I-III were 26.98 ± 2.64, 24.72 ± 4.49, 27.96 ± 2.02, respectively. HIV patients with neuropsychiatric manifestations (Group II) were noted to have the lowest MMSE score when compared to Group I and III. There was a significant difference in the mean MMSE score of Group I versus Group II (P = 0.012) and of Group III versus Group II (P < 0.001). The median HAM-A scale values were 4 (3, 8), 4 (4, 8) and 4 (2, 6) in Groups I-III, respectively. The baseline median HAM-D scores were 8 (5.75, 10), 8 (6, 14), and 6 (4, 10) in Groups I-III, respectively. HIV groups with neuropsychiatric symptoms and tuberculosis had higher score compared to asymptomatic HIV patients. Patients in Group II showed an association with abnormal neuropsychiatric assessment using MMSE/HAM-D/HAM-A (χ2 = 7.843; P = 0.005).
Median CD4 count (in cells/μL) in the HIV cohort in Groups I, II, III was 125.5 (62.25, 271.25); 89 (46.75, 175.75); 282 (135.50, 611.75), respectively. Statistically, significant difference in the median CD4 counts existed between Groups I and III (P < 0.001) and also between Groups II and III (P < 0.001). Pearson's correlation between CD4 count and Vitamin B6 revealed that there exists a weak positive correlation between the CD4 count and Vitamin B6 (r = 0.181, P = 0.03). After subgroup analysis, it was found that there was a significant correlation between CD4 count and Vitamin B6 [Figure 1] in Group I (r = 0.391, P = 0.006), but there was no significant correlation between CD4 count and Vitamin B6 in Group II (P = 0.135) and Group III (P = 0.537).
|Figure 1: Correlation between CD4 count and Vitamin B6 in HIV patients with tuberculosis|
Click here to view
| Discussion|| |
In this study, 150 HIV-positive patients were enrolled and categorized into groups as mentioned in the methodology. Among them, 72% were males and 28% were females, while in a study conducted by Jam et al.,  the percentage of males in the study was 87% and females only 13%. The mean age was comparable between the three HIV groups. In the study conducted by Jiamton et al.  , the median age was 32 years. The mean hemoglobin level was statistically low in Groups I and II compared to Group III, signifying that advanced HIV disease may result in low hemoglobin. The prevalence of anemia in this study was 50% and the hemoglobin levels ranged from 4.2 to 17 g/dL. Anemia is a common finding in HIV-infected patients and is associated with serious implications.  MMSE score was lowest in Group II as they had specific neuropsychiatric problems. HAM-D scores were higher in Groups I and II compared to Group III because of the advanced nature of the disease in both groups and specific central nervous system involvement in Group II. Neurological disorder is due to neuronal loss as a result of HIV infection and may also be associated with Vitamin B6 deficiency. Active form of pyridoxine, pyridoxyl-5'- phosphate, is an essential cofactor for metabolism of tryptophan and synthesis of neurotransmitters such as serotonin which plays a role in regulation of mood, specifically depression.  The median Vitamin B6 levels were least in Group I, i.e., HIV patients with tuberculosis, which was 8.23 ng/ml compared to Groups II and III whose median Vitamin B6 values were 8.5 ng/ml and 11.12 ng/ml, respectively, as these patients were manifesting a coexistent tubercular infection which leads to increased oxidative stress. In addition, a few of the subjects were already on isoniazid at the time of enrollment, which would have led to pyridoxine deficiency. These patients may require high dose of Vitamin B6 supplementation to counteract the toxic effects of INH. The prevalence of Vitamin B6 deficiency was highest in Group II, i.e., HIV with neuropsychiatric manifestations with 28.3% of the individuals manifesting pyridoxine deficiency compared to 18.8% in Group I and 10% in Group II. We found a positive association of pyridoxine deficiency with Group II. A few studies have shown a significant correlation of lower level of serum pyridoxal-5'- phosphate level, with increased severity of depression in patients with depression. , In patients living with HIV, neuropsychiatric manifestations could be due to the disease itself or some peripheral triggers;  could it be pyridoxine deficiency? This suggests that pyridoxine supplementation is necessary for all HIV patients regardless of coinfection such as tuberculosis. On clinical assessment, abnormal neuropsychiatric score had a positive association with Group II; hence, early screening for depression, cognitive impairment, and anxiety is necessary for improving the quality of life and for better outcome in the patients on treatment. Individuals in Group II had advanced illness with low CD4 counts compared to other groups leading to increased incidence of various opportunistic infections mostly GI infections causing deficiency of micronutrients due to malabsorption. Furthermore, because of high viral load, the oxidative stress may be high and patients develop vitamin deficiencies. Prevalence of Vitamin B6 deficiency in HIV-positive homosexual men is around 10%-30% while it is 20% in this study. 
Baum et al. have commented on the role of Vitamin B6 though not as a primary etiological factor in the immune dysregulation seen in the early stage of HIV.  In our study, there was a weak positive correlation between CD4 count and pyridoxine levels. With the increase in the severity of the disease, there could be increased catabolism and increased turnover of the micronutrients leading to a precipitous fall in their levels. Hence, with increasing severity of the illness, the incidence of pyridoxine deficiency increases. This finding warrants the supplementation of pyridoxine even in all HIV patients. The limitation of the study was that the other confounding factors for pyridoxine deficiency were not matched between the groups . Further research to study whether supplementation of pyridoxine and other micronutrients in HIV-positive patients increases the period of symptom-free survival is required.
| Conclusion|| |
Increased proportion of pyridoxine deficiency is seen in individuals with HIV. Proportion of pyridoxine deficiency is also higher in HIV patients with neuropsychiatric manifestations. HIV patients with neuropsychiatric symptoms and tuberculosis have a low CD4 count and Vitamin B6 levels compared to HIV patients without neuropsychiatric symptoms or tuberculosis. A weak correlation was seen between pyridoxine levels and immune status of the patients.
We thank ICMR for the financial support for conducting the study.
Financial support and sponsorship
The study was funded by the ICMR.
Conflicts of interest
There are no conflicts of interest.
| References|| |
Beach RS, Mantero-Atienza E, Shor-Posner G, Javier JJ, Szapocznik J, Morgan R, et al
. Specific nutrient abnormalities in asymptomatic HIV-1 infection. AIDS 1992;6:701-8.
Semba RD, Tang AM. Micronutrients and the pathogenesis of human immunodeficiency virus infection. Br J Nutr 1999;81:181-9.
Baum MK, Shor-Posner G, Lu Y, Rosner B, Sauberlich HE, Fletcher MA, et al
. Micronutrients and HIV-1 disease progression. AIDS 1995;9:1051-6.
Baum MK, Mantero-Atienza E, Shor-Posner G, Fletcher MA, Morgan R, Eisdorfer C, et al
. Association of Vitamin B6 status with parameters of immune function in early HIV-1 infection. J Acquir Immune Defic Syndr 1991;4:1122-32.
Semba RD, Lyles CM, Margolick JB, Caiaffa WT, Farzadegan H, Cohn S, et al
. Vitamin A supplementation and human immunodeficiency virus load in injection drug users. J Infect Dis 1998;177:611-6.
Graham NM, Sorensen D, Odaka N, Brookmeyer R, Chan D, Willett WC, et al
. Relationship of serum copper and zinc levels to HIV-1 seropositivity and progression to AIDS. J Acquir Immune Defic Syndr 1991;4:976-80.
Tang AM, Graham NM, Kirby AJ, McCall LD, Willett WC, Saah AJ. Dietary micronutrient intake and risk of progression to acquired immunodeficiency syndrome (AIDS) in human immunodeficiency virus type 1 (HIV-1)-infected homosexual men. Am J Epidemiol 1993;138:937-51.
Fawzi WW, Msamanga GI, Spiegelman D, Wei R, Kapiga S, Villamor E, et al
. A randomized trial of multivitamin supplements and HIV disease progression and mortality. N Engl J Med 2004;351:23-32.
Kanter AS, Spencer DC, Steinberg MH, Soltysik R, Yarnold PR, Graham NM. Supplemental Vitamin B and progression to AIDS and death in black South African patients infected with HIV. J Acquir Immune Defic Syndr 1999;21:252-3.
Tang AM, Graham NM, Semba RD, Saah AJ. Association between serum Vitamin A and E levels and HIV-1 disease progression. AIDS 1997;11:613-20.
Tang AM, Graham NM, Chandra RK, Saah AJ. Low serum Vitamin B-12 concentrations are associated with faster human immunodeficiency virus type 1 (HIV-1) disease progression. J Nutr 1997;127:345-51.
Jiamton S, Pepin J, Suttent R, Filteau S, Mahakkanukrauh B, Hanshaoworakul W, et al
. A randomized trial of the impact of multiple micronutrient supplementation on mortality among HIV-infected individuals living in Bangkok. AIDS 2003;17:2461-9.
Tang AM, Graham NM, Saah AJ. Effects of micronutrient intake on survival in human immunodeficiency virus type 1 infection. Am J Epidemiol 1996;143:1244-56.
NACO. HIV Testing Manual: Laboratory Diagnosis, Bio-Safety and Quality Control. New Delhi: NACO India Publications; 1999. p. 52-69.
Jam S, Ramezani A, Sabzvari D, Moradmand-Badie B, Seyedalinaghi S, Jabbari H, et al
. A cross-sectional study of anemia in human immunodeficiency virus-infected patients in Iran. Arch Iran Med 2009;12:145-50.
Ferede G, Wondimeneh Y. Prevalence and related factors of anemia in HAART-naive HIV positive patients at Gondar University Hospital, Northwest Ethiopia. BMC Hematol 2013;13:8.
Merete C, Falcon LM, Tucker KL. Vitamin B6 is associated with depressive symptomatology in Massachusetts elders. J Am Coll Nutr 2008;27:421-7.
Hvas AM, Juul S, Bech P, Nexø E. Vitamin B6 level is associated with symptoms of depression. Psychother Psychosom 2004;73:340-3.
Dubé B, Benton T, Cruess DG, Evans DL. Neuropsychiatric manifestations of HIV infection and AIDS. J Psychiatry Neurosci 2005;30:237-46.
[Figure 1], [Table 1], [Table 2]