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Effect of Micronutrient on HIV Infected Patients Receiving Highly Active Antiretroviral Therapy and Its Implication on Markers of Renal Disease

Research Article                                          Vol:1,Issue:2

Raphael Avidime Attah, Catherine Ojebbah Attah, Mustapha Jibril Muhammed

Abstract 

As patients infected with human immunodeficiency virus (HIV) live longer while on highly active antiretroviral therapy (HAART), kidney diseases have emerge as significant cause of morbidity and mortality among them. The effect of micronutrient in HIV infected patients on highly active antiretroviral therapy and its implication on markers of renal disease was evaluated. A randomized control trial where serum vitamins A, C, & E, Creatinine, urea, sodium, potassium, chloride, bicarbonate, CD4+Count, BMI, Zinc and Selenium were measured in 120 (randomly selected) HIV infected patients already on HAART at S. S. Walli virology center in Aminu Kano Teaching Hospital (AKTH). After their baseline assessment, 60 of these patients were randomly selected and placed on micronutrient supplementation for three (3) months and the remaining 60 were not given micronutrient supplement for the same period. There was significant increase (p< 0.05) in vitamin A, C, E, CD4 count, BMI, selenium, and GFR of supplemented group compared to their corresponding baseline. While there was significant decrease in zinc, Creatinine, and urea of supplemented group compared to
their corresponding baseline. Significant difference (p>0.05) was not found in sodium, potassium, chloride, bicarbonate of supplemented group compared to their corresponding baseline. There was significant increase (p <0.05) in serum vitamin A, E, CD4 count, zinc, selenium, creatinine, urea of non-supplemented group compared to their baseline. While there as significant decrease in serum BMI and GFR of the non-supplemented group compared to their baseline. Significant difference (p>0.05) was not found in serum vitamin C, sodium, potassium, chloride and bicarbonate of non-supplemented group compared to their baseline. There was significant increase (p<0.05) in serum vitamin A, C, E, zinc, selenium, BMI, CD4 count and GFR of supplemented group compared to the nonsupplemented group. While there was significant decrease (P<0.05) in serum creatinine and urea in supplemented group compared to the non-supplemented group. 
This study shows that micronutrient supplementation may be a beneficial adjunct to HAART and may also improve renal function in HIV infection.

SAJMED.2016; 1(2):22-28                                                          PDF Download

Introduction

Over 40 million people worldwide are believed to be living with HIV or AIDS (1). HIV/AIDS remains a global problem despite all the effort and measures taken to control its spread in the last two decades. HIV is a Lentivirus, a subgroup of retroviruses. This family of viruses is known for latency, persistent viremia, infection of the nervous system, and weak host immune responses. HIV has high affinity for CD4 T lymphocytes and monocytes(2). CD4 cells are a type of white blood cell that fights infection. Another name for them is Thelper cells. CD4 cells are made in the spleen, lymph nodes, and thymus gland, which are part of the lymph or infection-fighting system. CD4 cells move throughout the body, helping to identify and destroy germs such as bacteria and viruses. The CD4 count measures the number of CD4 cells in a sample of blood drawn by a needle from a vein in the arm. Along with other tests, the CD4 count helps tell how strong the immune system is, indicates the stage of HIV disease, guides treatment, and predicts how the disease may progress. Keeping the CD4 count high can reduce complications of HIV disease and extend life(3). The relationship between immune function and nutritional supplementation is a well-described phenomenon(4, 5). Numerous studies have reported a high prevalence of nutrient deficiencies early in the course of HIV infection(6, 7). These deficiencies have been shown to be associated with more frequent
opportunistic infections, faster disease progression, and a greater incidence of HIV related mortality. (8, 9) Possible mechanisms include increased intracellular oxidative stress, enhanced viral replication, and a reduction in the number of circulating CD4 lymphocytes associated with individual or accumulated nutrient deficiencies(10, 11). These mechanisms, alone or in part, may contribute to the increased morbidity, more rapid disease progression, and the higher mortality seen in HIV-infected patients with nutrient deficiencies(12, 8). The positive effect of micronutrient supplements in HIV patients goes beyond their positive effect on the immune system, they improve mood, depression, quality of life, energy levels, capacity to exercise, and [illnesses] among other factors of daily living. The supplements in the studies contain micronutrients, which are vitamins and minerals that the body needs in very small amounts to produce enzymes, hormones, and other substances necessary for growth and development(13). To determine the effect of micronutrient in HIV infected patients on highly active antiretroviral therapy and to determine its implication on marker of renal disease. This was achieved by the following objectives: Taking a baseline data of the recruited patients. This involves assaying for
micronutrients such as vitamin A, vitamin C, vitamin E and some trace elements such as zinc and selenium. This will be repeated three months after supplementing these patients. The effect of the above will be determined on markers of renal disease. Assessing the nutritional status of the patients using anthropometric indices of weight, height to determine the BMI of the patients before and after supplementation. GFR (Glomerular filtration rate) was used to dictate the state of their kidney using Cockcroft & Gault equation (14).

Materials And Methods

This Study is mainly a prospective study involving 120 HIV-infected patients that were managed at the Outpatient Unit of S.S. Wali virology Center Aminu Kano Teaching Hospital (AKTH) Kano, over a period of six (6) months. All participants were above 13 years of age. Exclusion criteria include children below 13 years of age and pregnant women. A 24hr recall form was provided for both quantitative and qualitative dietary assessment of each patient so as to draw conclusions on the nutritional status of each patient. In addition, micronutrients such as vitamin A, vitamin C, and E, zinc and selenium were administered and assayed, as well as: The demographic and social characteristics of the patient with HIV. Relationship with sexual orientation. Complication of renal disease and treatment as measured by its markers. BMI as a measure of response to treatment.

Results

Table 1 presents the mean serum vitamin A, C and E, Zinc and Selenium, Body Mass Index (BMI), CD4+ count, Creatinine, GFR, Urea, and electrolytes in the supplemented group and their corresponding baseline. There is significant difference between the mean serum vitamin A, C and E, of supplemented group 41.40µg/dL, 4.22mg/dL, 26.91µg/dL compare with that of their corresponding baseline 21.46µg/dl, 0.47mg/dl, 0.17µg/dl respectively (P < 0.05). There is also a significant difference in mean serum selenium, BMI, CD4+ count in the supplemented group 23.99µg/dL, 26.63Kg/m2, 442.74cell/mm3 when compared to their corresponding baseline 22.61 µg/dL, 24.99 Kg/m2, 321.96 cell/mm3 respectively. No significant difference (P <0.05) in mean serum of Zinc, sodium, potassium, chloride and bicarbonate in the supplemented group 64.78 µg/dL, 138.40 mmol/L, 4.88 mmol/L, 102 mmol/L, 22.00 mmol/L compared to their corresponding baseline 65.07 µg/dL, 135 mmol/L, 5.04 mmol/L, 99.50 mmol/L, and 23.16 respectively. Significant difference is observed in Creatinine, GFR and urea of supplemented group 72.27 mmol/L, 93.82mL/min/1.73, 4.17mmol/L compare with that of their corresponding baseline 97.64 mmol/L, 53.63mL/min/1.73, and 3.08 mmol/L. Table 2 compare serum vitamin A, C, and E, Zinc and Selenium, BMI, CD4+ count, creatinine, GFR, urea and electrolytes of supplemented and non-supplemented group. There is significant difference p<0.05 in the mean serum of vitamin A, C and E, Zinc, Selenium, BMI and CD4count of supplemented
group 41.40µg/dL, 4.22mg/dL, 26.91 µg/dL, 64.78 µg/dL, 23.99 µg/dL, 26.63kg/m2, 442.74cell/mm3 compare to the nonsupplemented group 35.33 µg/dL, 0.71mg/dL, 1.38 µg/d, 66.30 µg/dL, 25.63 µg/dL, 22.96 kg/m2 , 296.00cell/mmol. There is also significant difference in the serum level of Creatinine, GFR and urea of the supplemented group 72.27mmol/L, 93.82 mL/min/1.73, and 4.17mmol/L as compare to their nonsupplemented counterpart 97.64mmol/L, 53.63 mL/min/1.73 and 3.08mmol/L. There is no statistical significant change in the serum level of electrolyte sodium, potassium, chloride and bicarbonate of the supplemented group 138.40 mmol/L, 4.88 mmol/L, 102mmol/L, 22.00 mmol/L compare to their non- supplemented counterpart 137.20 mmol/L, 4.96 mmol/L, 98.40 mmol/L, 23.88 mmol/L respectively. Table 3 presents the approximate values of the daily macronutrients, micronutrients and energy intake of patients under the study. This was obtained from the 24 hours food recalls recorded in part 2 of the questionnaire used for the study. Observation from the table shows that, 26.7% of the studied subjects meet up with the Recommended Daily Intake (RDI) of carbohydrate (130g/day), 25.8% takes the RDI of lipids (52g/day for males and 46g/day for females), while only 8.3% of the studied patients takes the RDI of protein (52g/day). This indicates that less than 30% of the studied patients take the RDI of the macronutrients. About 10.8% takes the RDI of vitamin C (75mg/day), 22.5% takes the RDI of vitamin E, while none of the patients takes the RDI of vitamin A (900 μg/day). Only 15% of these subjects takes the RDI of zinc while, none of
the patients takes the RDI of selenium. This also predicts that less than 30% of the studied subjects take the RDI of the studied micronutrients.

Discussion

The present study shows that micronutrient supplementation has beneficial effect on HIV seropositive patients both on HAART and
HAART naive and an improvement of renal function. This is seen in table 3 of this study,
when comparing group on supplementation and group not on supplementation and also group on supplementation and its baseline (table 1). This is in line with (15, 16). In an observational study comparing HIV positive person, it was observed that HIV infected person have lower or deficient serum concentration of several micronutrients and more commonly thiamine, selenium, zinc and vitamin A, B-3, B-6, B-12, C, D, and E to be individually associated with low CD4 cell count, advance HIV related disease and faster disease progression or HIV related
mortality.(17) also in a placebo control of HIV infected adults placed on a daily supplement of vitamin A, C, E for 6 months. At baseline, concentration of vitamin A, C and E were significantly lower compared with a small group of HIV negative healthy volunteers. At follow up, concentrations of vitamin A, C and E increased significantly in supplemented group than the placebo group. Observation from the result of the study shows an increase in level of selenium in the supplemented group. This finding agrees with (18). In a placebo control trial, 186 HIVpositive adult placed on selenium for 2 years, 85 of them on HAART. The 2 groups had similar level of selenium at baseline. At followup, the supplemented group had a higher serum selenium level, less risk of decrease CD4 cell count and decrease hospital admission in the patients.
The result also shows an increase in the level of CD4 cell count, decrease in creatinine and
subsequently increases the GFR (glomerular filtration rate) and decrease in urea in the supplemented group and its corresponding
baseline and also comparing supplemented group and non-supplemented group. This agrees with (19). In a randomized controlled
trial conducted in 40 HIV infected adults found that comprehensive micronutrients supplementation for 12 weeks significantly
increased the CD4 cell count. The decrease observe in creatinine and urea could be as a result of the physiologic role played by the micronutrients supplementation that increased the CD4 count which then led to increase in the glomerular filtration rate, as observe in table 1 and 2. This is consistent with (20). A CD4 count <200 cells/kl, remained an independent predictor of experiencing AKI and
the most important predictor of HIV-1-related morbidity and mortality. There is no statistically significant difference in the electrolyte (sodium, potassium, chloride, bicarbonate) measured between the supplemented group and the corresponding baseline as indicated in table 1. The result of the present study indicates increase in BMI in the supplemented group compare with its corresponding baseline.
HIV infection increases the oxidative stress process, which is further increased by the use of antiretroviral therapy (ART) (21, 22). This is evidenced by the elevation in the level of creatinine and urea observed in the nonsupplemented subjects.