Effects of selenium supplementation on pregnancy outcome and disease progression in HIV-infected pregnant women in Lagos, Nigeria: Study protocol for a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Micronutrient deficiencies are common during pregnancy, especially in pregnant women from economically disadvantaged settings where diets with low content of minerals and vitamins are consumed. Selenium is a non-metallic chemical element of great importance to human health. This study will assess the effect of selenium supplementation on major pregnancy outcomes and disease progression among HIV-infected pregnant women in Lagos, Nigeria. METHODS: A randomized, double-blind, placebo-controlled trial involving confirmed HIV-positive pregnant women at the Lagos University Teaching Hospital (LUTH) between September 2018 and February 2019. Eligible participants are HIV-infected pregnant women aged 15 to 49 years and have a singleton gestation at 14 to 27 weeks' gestation. At enrolment, 90 women will be randomly assigned into each intervention arm to receive either a daily tablet of 200 µg elemental selenium or placebo. Relevant participants' data will be collected at enrolment and at delivery. Statistical analyses will be carried out using SPSS version 23.0 for Windows. The associations between any 2 groups of continuous variables will be tested using the t test or the Mann-Whitney U test and that of 2 groups of categorical variables with chi-square or Fishers exact test where appropriate. A series of multivariable analyses will also be carried out to identify and control for several possible confounders of the major pregnancy outcomes and HIV disease progression. Statistical significance will be defined as P < .05. Ethical approval for the study was obtained from the LUTH's Health Research and Ethics Committee (Approval number: ADM/DCST/HREC/APP/2438; 30th August 2018). DISCUSSION: This trial will assess the effect of selenium supplementation on pregnancy outcome and HIV disease progression among HIV-infected pregnant women in Lagos. This will help to determine if routine selenium supplementation in HIV-infected pregnant women will contribute to the improvement in the major adverse pregnancy outcomes such as preterm birth and low birth weight and the HIV disease surrogate markers such as CD4+ cells count and viral load. TRIAL REGISTRATION: PACTR, PACTR201809756724274. Registered on 3rd September 2018, https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=3571.

A randomized, controlled trial of mindfulness-based stress reduction in HIV infection.

OBJECTIVE: Evidence links depression and stress to more rapid progression of HIV-1 disease. We conducted a randomized controlled trial to test whether an intervention aimed at improving stress management and emotion regulation, mindfulness-based stress reduction (MBSR), would improve immunological (i.e. CD4+ T-cell counts) and psychological outcomes in persons with HIV-1 infection. METHODS: We randomly assigned participants with HIV-1 infection and CD4 T-cell counts >350 cells/µl who were not on antiretroviral therapy in a 1:1 ratio to either an MBSR group (n = 89) or an HIV disease self-management skills group (n = 88). The study was conducted at the University of California at San Francisco. We assessed immunologic (CD4, c-reactive protein, IL-6, and d-dimer) and psychological measures (Beck Depression Inventory for depression, modified Differential Emotions Scale for positive and negative affect, Perceived stress-scale, and mindfulness) at 3, 6 and 12 months after initiation of the intervention; we used multiple imputation to address missing values. RESULTS: We observed statistically significant improvements from baseline to 3-months within the MBSR group in depression, positive and negative affect, perceived stress, and mindfulness; between group differences in change were significantly greater in the MBSR group only for positive affect (per item difference on DES-positive 0.25, 95% CI 0.049, 0.44, p = .015). By 12 months the between group difference in positive affect was not statistically significant, although both groups had trends toward improvements compared to baseline in several psychological outcomes that were maintained at 12-months; these improvements were only statistically significant for depression and negative affect in the MBSR group and perceived stress for the control group. The groups did not differ significantly on rates of antiretroviral therapy initiation (MBSR = 39%, control = 29%, p = .22). After 12 months, the mean decrease in CD4+ T-cell count was 49.6 cells/µl in participants in the MBSR arm, compared to 54.2 cells/µl in the control group, a difference of 4.6 cells favoring the MBSR group (95% CI, -44.6, 53.7, p = .85). The between group differences in other immunologic-related outcomes (c-reactive protein, IL-6, HIV-1 viral load, and d-dimer) were not statistically significant at any time point. CONCLUSIONS: MBSR improved positive affect more than an active control arm in the 3 months following the start of the intervention. However, this difference was not maintained over the 12-month follow-up and there were no significant differences in immunologic outcomes between intervention groups. These results emphasize the need for further carefully designed research if we are to translate evidence linking psychological states to immunological outcomes into evidence-based clinical practices.

An 84-month observational study of the changes in CD4 T-lymphocyte cell count of 110 HIV/AIDS patients treated with traditional Chinese medicine.

This study aimed to evaluate the therapeutic effect of traditional Chinese medicine (TCM) by observing the changes in CD4 T-lymphocyte cell count of 110 cases with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) treated continuously with TCM for 84 months. Information of 110 HIV/AIDS patients from 19 provinces and cities treated with TCM from 2004 to 2013 was collected. Changes in the indexes of CD4 counts ( ≤ 200, 201-350, 351-500 and > 500 cells/mm(3)) at five time points (0, 12, 36, 60 and 84 months) and different treatments [TCM and TCM plus antiretroviral therapy (ART)] were compared. Repeated measures test indicated no interaction between group and time (P > 0.05). Degrees of increasing and decreasing CD4 count of the two groups at four different frames were statistically significant compared with the baseline. The CD4 count between the two groups was not statistically significant. For CD4 count of ≤ 200 cells/mm(3), the mean CD4 count changes were 21 and 28 cells/mm(3) per year for the TCM group and TCM plus ART group, respectively. For CD4 count of 201-350 cells/mm(3), the mean CD4 count changes were 6 and 25 cells/mm(3) per year for the TCM group and TCM plus ART group, respectively. For CD4 count of 351-500 cells/mm(3), the mean CD4 count changes were -13 and -7 cells/mm(3) per year for the TCM group and TCM plus ART group, respectively. For CD4 count of > 500 cells/mm(3), the mean CD4 count changes were -34 and -17 cells/mm(3) per year for the TCM group and TCM plus ART group, respectively. Long-term use of TCM could maintain or slow the pace of declining CD4 counts in patients with HIV/AIDS, and may achieve lasting effectiveness.

Validation of a single-platform, volumetric, flow cytometry for CD4 T cell count monitoring in therapeutic mobile unit.

BACKGROUND: A mobile health unit may be useful to follow up adult and pediatric patients on antiretroviral treatment and living in remote areas devoid of laboratory facilities. The study evaluated the use of the simplified, robust, single-plateform, volumetric, pan-leucogating Auto40 flow cytometer (Apogee Flow Systems Ltd, Hemel Hempstead, UK) for CD4 T cell numeration in a mobile unit, compared against a reference flow cytometry method. METHODS: The therapeutic mobile unit of the Laboratoire National de Santé Hygiène Mobile, Yaoundé, Cameroon, was equipped with the Auto40. A FACSCalibur flow cytometer (Becton Dickinson Immuno-cytometry System, San Jose, CA, USA) was used as reference method. EDTA-blood samples from volunteers were first subjected to CD4 T cell count in the mobile unit, and an aliquot was sent within 4 hours to Centre International de Référence Chantal Biya, Yaoundé, for FACSCalibur assay. RESULTS: Two HIV screening campaigns with the mobile unit were organised in December 2009 and January 2010. The campaign in the suburb of Yaoundé which was 20 km from the reference laboratory included 188 volunteers comprising 93 children less than 5 years old. The campaign in Ambang Bikok (53 km far from Yaoundé) included 69 adult volunteers. In Yaoundé suburb, mean ± standard deviation (SD) CD4 T cell count was 996 ± 874 cells/µl by Auto40, and 989 ± 883 cells/µl by FACSCalibur; in Ambang Bikok, mean ± SD CD4 T cell count was 1041 ± 317 cells/µl by Auto40, and 1032 ± 294 cells/µl by FACSCalibur. Results by Auto40 and FACSCalibur were highly correlated in Yaoundé (r(2) = 0.982) as in Ambang Bikok (r(2) = 0.921). Bland-Altman analysis showed a close agreement between Auto40 and FACSCalibur results expressed in absolute count as in percentage in Yaoundé and Ambang Bikok. When pooling the 257 CD4 T cell count measurements, the Auto40 yielded a mean difference of +7.6 CD4 T cells/µl higher than by reference flow cytometry; and the sensitivity and specificity of Auto40 in enumerating absolute CD4 T cell counts of less than 200 cells/µl were 87% and 99%, respectively, and in enumerating absolute CD4 T cell counts of less than 350 cells/µl were 87% and 98%, respectively. The intrarun and interun precisions of the Auto40 assay assessed in the mobile unit were 5.5% and 7.9%, respectively. CONCLUSIONS: The Auto40 flow cytometer installed in a therapeutic mobile unit and operated far from its reference laboratory gave a perfect correlation with the reference method, and could be useful in carrying out immunological monitoring of HIV-infected patients living in areas without access to laboratory facilities.

Role of certain trace minerals in oxidative stress, inflammation, CD4/CD8 lymphocyte ratios and lung function in asthmatic patients.

BACKGROUND: Asthma is associated with increased inflammation, oxidative stress and abnormal immune system function. We determined the distributions of several essential trace minerals and assessed their relationships to factors that are associated with the pathophysiological status of patients with mild/moderate asthma. METHODS: We enrolled 25 asthmatic patients and 25 healthy subjects. We measured: blood trace minerals, zinc (Zn), copper (Cu) and selenium (Se); oxidative stress markers thiobarbituric acid reactive substances (TBARS); antioxidant enzyme activities; percentages of CD4 and CD8 lymphocyte subsets; high-sensitivity C-reactive protein (hs-CRP); and a lung function index (FEV1/FVC%). RESULTS: Compared with healthy subjects, asthmatics had lower concentrations of Zn and Se; higher Cu concentrations, and Cu/Zn and Cu/Se ratios; and lower antioxidant enzyme glutathione peroxidase (GPx), glutathione reductase (GR) and catalase activities. Significantly increased concentrations of hs-CRP, TBARS and CD4/CD8 lymphocyte ratios were also observed. Furthermore, plasma TBARS or hs-CRP concentrations were negatively associated with Se concentrations, but were positively associated with Cu/Se ratios. CD4/CD8 lymphocyte ratios were inversely correlated with Se, while it was positively correlated with Cu/Se ratio. FEV1/FVC% was also significantly correlated with Se concentrations, and Cu/Se and Cu/Zn ratios. CONCLUSIONS: Abnormal distributions of these trace minerals may aggravate oxidative damage and inflammation, increased CD4/CD8 lymphocyte ratios and decreased lung function in asthma.

Reduction of CD4 positive T cells and improvement of pathological changes of collagen-induced arthritis by FTY720.

FTY720 belongs to a new class of immunosuppressants. Little is known about its influence on T cell subtypes and pathological changes in arthritis. Here we illustrated the effect of FTY720 on peripheral T cell subsets and joint damage of collagen-induced arthritis rats. Rats were administered FTY720 or prednisone daily from day 0 to day 28. Body weight, hind paw swelling and arthritis index were measured. Bone destruction was determined by micro-computed tomography and histopathology, and T cell subsets were analyzed by flow cytometry and immunohistochemistry. The results showed that FTY720 inhibited the development of arthritis. Radiological analysis revealed that FTY720 treated collagen-induced arthritic rats had much less joint damage in comparison to untreated collagen-induced arthritic rats. Histological study showed that collagen-induced arthritic rats suffered from inflammatory cell infiltration and synovial hyperplasia in their joints, and FTY720 treatment clearly reduced these pathological changes. Immunohistochemical analysis showed that FTY720 treatment significantly decreased the number of CD4(+) T cells in the synovium of collagen-induced arthritic rats. Collagen-induced arthritic rats appeared to have more CD4(+), but not CD8(+) T cells in their peripheral blood than normal control rats. Following FTY720 treatment, peripheral blood CD3(+) and CD4(+) T cells in collagen-induced arthritic rats were significantly decreased. In conclusion, FTY720 is an effective compound in the treatment of collagen-induced arthritic rats and in reducing CD4(+) T cells in collagen-induced arthritic rats.

Relación entre la ingesta de ácidos grasos omega 3 y los valores de CD4 en pacientes con infección por VIH: un estudio transversal / Relation between intake of omeda 3 fatty acids and CD4 count in patients with Hiv infection: a transversal study

Objetivos: Los ácidos grasas poliinsaturados, son agentes inmunomoduladores. Estos nutrientes podrían tener un papel relevante en los pacientes con infección por VIR. El objetivo de nuestro trabajo fue analizar la relación entre la ingesta de ácidos grasas poliinsaturados y los niveles de linfocitos CD4 en estos pacientes.Pacientes y métodos: Un total de 40 pacientes con infección por VIR fueron estudiados. En todos los pacientes se registraron las siguientes variables; edad, sexo, tratamiento antiretroviral y se realizó una evaluación antropométrica (peso, pliegue tricipital, circunferencia muscular, índice de masa corporal (IMC», así como una valoración bioquímica (albúmina, prealbúmina, transferrina, proteínas totales, linfocitos totales y recuento de CD4). A todos los pacientes se les realizó una encuesta nutricional de 3 días.Resultados: La edad media de los 40 pacientes (24 varones y 16 mujeres) fue de 37,6 +/- 9,4 años, peso 65,6 +/- 12,2 kg e índice de masa corporal 23,2 +/- 3,25. La evaluación antropométrica mostró un valor medio del pliegue tricipital de 15,1 +/- 5,3 mm, circunferencia muscular del brazo 27,5 +/- 3,1 cm. La ingesta calórica y la distribución de macronutrients fue normal.(carbohidratos 48%, proteínas 18% y lípidos 34%). La ingesta de ácidos grasas poliinsaturados fue la siguiente; ácidos omega 3 (1,22 +/- 3,1 g/día), ácidos omega 6 (5,76 +/- 4,6 g/día) y ácidos omega 9 (31,5 +/- 11 g/día). En el análisis multivariante, con los niveles de CD4 como variable dependiente, mostró como variable independiente los niveles de omega 3 (F = 6,2; p < 0,05), con un incremento de 32 CD4 (IC95%: 9,86-52,14) CD4+ (recuento/uL) por cada 1 g de ácidos omega 3 ajustado por edad, sexo y fármaco s antiretrovirales.Conclusión: En pacientes con infección por VIH, la ingesta de ácidos grasas omega 3 se correlaciona con un incremento de los valores de CD4

Objectives: Polyunsaturated fatty acids are immunomodulatory agents. These agents could develop a main role in patients with HIV infection. The aim of our study was to analyse the relation between polyunsaturated fatty acid intake and CD4 count in HIV infected patients. Patients and methods: Forty patients with HIV infections were enrolled. In all patients, the next variables were recorded; age, sex, drugs, anthropometric evaluation (weight, height, tricipital skinfold, midarm circumference, body mass index) and a biochemical evaluation (albumin, prealbumin, trasferrin, total proteins, total lymphocytes and CD4 count). A 3 day dietary intake questionnaire was performed, too. Results: The mean age was (24 males and 16 females) 37.6 +/- 9.4 years, mean weight 65.6 +/- 12.2 kg and body mass index 23.2 +/- 3.25. Anthropometric evaluation showed a mean tricipital skinfold of 15.1 +/-5.3 mm, midarm circumference 27.5 +/- 3.1 cm. Caloric intake and macronutrient distribution were normal (carbohydrates 48%, proteins 18% and lipids 34%). Dietary intake of polyunsaturated fatty acids was omega 3 (1.22 +/-3.1 g/day) and omega 9 (3.5+/-11 g/day). Multivariante analysis, with CD4 count as a dependent variable, showed omega 3 intake as a independent variable (F = 6.2; p < 0.05), with an increase of 32 (IC95%: 9.86-52.14) CD4+ (count/uL) with each 1 g of omega 3 dietary intake adjusted by age, sex, and drugs. Conclusion: In patients with HIV infection, dietary intake of omega 3 fatty acids increase CD4 count

Korean red ginseng slows depletion of CD4 T cells in human immunodeficiency virus type 1-infected patients.

We have previously showed that long-term intake of Korean red ginseng (KRG) delayed disease progression in human immunodeficiency virus type 1 (HIV-1)-infected patients. In the present study, to investigate whether this slow progression was affected by KRG intake alone or in combination with HLA factor, we analyzed clinical data in 68 HIV-1-infected patients who lived for more than 5 years without antiretroviral therapy. The average KRG intake over 111.9 +/- 31.3 months was 4,082 +/- 3,928 g, and annual decrease in CD4 T cells was 35.0 +/- 28.7/microl. Data analysis showed that there are significant inverse correlations between the HLA prognostic score (0.29 +/- 1.19) and annual decrease in CD4 T cells (r = -0.347; P < 0.01) as well as between the amount of KRG intake and annual decrease in CD4 T cells (r = -0.379; P < 0.01). In addition, KRG intake significantly slowed the decrease in CD4 T cells even when influence of HLA class I was statistically eliminated (repeated-measure analysis of variance; P < 0.05). We also observed significant correlation between KRG intake and a decrease in serum-soluble CD8 antigen level (r = 0.62; P < 0.001). In conclusion, these data show that KRG intake independently and significantly affected the slow depletion of CD4 T cells irrespective of HLA class I.