Serum Levels of Micronutrients, Magnesium, and Markers of Immunity (CD4+ ) in Antiretroviral-naïve HIV-infected Individuals: Relationships and Predictors.

BACKGROUND: HIV/AIDS may lead to micronutrient deficiencies and low CD4+ count. OBJECTIVES: We assessed the correlation of CD4+ count in antiretroviral-naïve patients with the serum levels of micronutrients as measures of the relationship between immunity and nutrition/malnutrition. METHODS: A case-control study of ninety consecutive newly diagnosed HIV/AIDS patients and ninety blood donors. Blood collected from controls and patients before HAART treatment were assayed for serum zinc, selenium, copper, manganese, and magnesium. RESULTS: The participants had non-significantly lower zinc (14.25±2.93µmol/l versus 14.58±3.69µmol/l, p=0.493), significantly lower selenium (0.38±0.08µmol/l versus 0.78±0.22µmol/l, p<0.001), manganese (7.06±0.87µmol/l versus 11.23±3.27µmol/l, p<0.001), and magnesium (1.02±0.21mmol/l versus 1.21±0.28mmol/l, p<0.001) when compared with the controls. The mean copper level was similar in both groups (18.88±3.1µmol/l and 18.82±5.12µmol/l, p=0.921). There was no correlation between the micronutrients and CD4+ count; however, there were strong positive correlations between the levels of zinc and copper, selenium, magnesium; copper and magnesium (p<0.001 respectively). Multivariate regression showed that all micronutrients were independent predictors of one another (p<0.001). CONCLUSION: HIV/AIDS results in serum micronutrient depletion with strong positive correlations between their levels; all micronutrients were independent predictors of one another. This significant positive relationships between the micronutrients, and magnesium; and all other micronutrients being independent predictors of each other signifies a synergistic or supportive relationship between micronutrient deficiencies and HIV/AIDS disease morbidity and progression. Serum micronutrients may not be qualified as direct markers or surrogates for CD4+ count in antiretroviral-naïve HIV-infected patients.

Effects of Highly Active Antiretroviral Therapy on Renal Function and Renal Phosphate Handling in African Adults with Advanced HIV and CKD.

BACKGROUND: Highly Active Antiretroviral Therapy (HAART) has been implicated in renal dysfunction with hypophosphataemia. OBJECTIVE: We prospectively evaluated renal phosphate excretion during HAART use. METHOD: Newly diagnosed human immunodeficiency virus (HIV)-infected individuals were treated with Tenofovir disoproxil fumarate/Emtricitabine/Efavirenz (TDF/FTC/EFV), n=33; Zidovudine/Lamivudine/Nevirapine (ZDV/3TC/NVP), n=53; and Zidovudine/Lamivudine/Efavirenz (ZDV/3TC/EFV), n=16. Creatinine and phosphate were assayed in blood and urine simultaneously at baseline, 1, 3, 6 and 9 months. Glomerular filtration rate (eGFR), fractional phosphate excretion and reabsorption (FEPi % and TRP), and the ratio of tubular maximum reabsorption of phosphate (TmP) to GFR (TmP/GFR) were estimated. RESULTS: At baseline, eGFR showed moderate chronic kidney disease (mean: 35.50 ± 2.02, 33.14 ± 1.63, and 39.97±1.84 ml/min/1.73m2 in the 3 groups respectively); 54 (52.9%) patients had hyperphosphataemia (>1.4mmo/L); 43 (42.2%) had normophosphataemia (0.6-1.4mmol/L); 5 (4.9%) had hypophosphataemia (<0.6mmol/L). eGFR improved significantly from 1 month (≥60, 58.65 ± 1.11, and 51.76 ±1.59 ml/min/1.73m2; p=0.04, <0.001, 0.67 respectively), with a relapse at 9 months in TDFtreated subjects (50.10 ± 1.89 ml/min/1.73m2). TDF/FTC/EFV resulted in significantly greater reduction in plasma phosphate than ZDV/3TC/NVP (p=0.031), but not significantly different from ZDV/3TC/EFV (p=0.968). Similarly, ZDV/3TC/EFV resulted in significantly greater reduction in plasma phosphate than ZDV/3TC/NVP (p=0.036). FEP% progressively increased with HAART duration, more in TDF-treated and ZDV/3TC/EFV-treated groups than ZDV/3TC/NVP (p=0.014); TRP was elevated (>0.86), implying non-maximal phosphate reabsorption. TmP/GFR values were elevated, (>1.35mmol/l). CONCLUSION: HIV causes kidney dysfunction with reduced phosphate excretion resulting in hyperphosphataemia but HAART improves renal function. Prolonged use of TDF can cause renal toxicity with hypophosphataemia as fractional excretion progressively increased with duration of therapy unlike ZDV/3TC/NVP. The use of different third agents (either NVP or EFV) in zidovudine-based therapy results in significantly different plasma phosphate levels; ZDV/3TC/EFV, like TDF/FTC/EFV, resulted in significantly greater decline in plasma phosphate than ZDV/3TC/NVP. Thus, Evafirenz (EVF) may have similar or synergistic adverse effects with tenofovir disoproxil fumarate (TDF).

Prevalence and Pattern of Chronic Kidney Disease in Antiretroviral-Naïve Patients with HIV/AIDS.

BACKGROUND: Chronic renal failure and HIV/AIDS are both prevalent in Nigeria. We performed a cross-sectional analysis of renal function in newly diagnosed, treatment-naive HIV-infected patients before initiating highly active antiretroviral therapy. METHODS: Treatment-inexperienced individuals were recruited. Patients with diabetes mellitus and hypertension were excluded. Plasma creatinine level was used to measure the estimated glomerular filtration rate ([eGFR] by Modification of Diet in Renal Disease equation). Predictors of creatinine and eGFR were determined by univariate and multivariate analyses. RESULTS: We evaluated 183 patients. In all, 44 (24%) patients had a GFR <60 mL/min/1.73 m(2), implying moderate chronic kidney disease (CKD). Considering the eGFR, 22 (12%) patients had stage 1, 117 (63.9%) stage 2, 13 (7.1%) stage 3, 27 (14.8%) stage 4, and 4 (2.2%) stage 5 CKD. Creatinine inversely correlated with CD4 (r = -.228, P = .025). CD4 predicts creatinine (odds ratio 1.6, 95% confidence interval 1.0-1.8, P = .003). CONCLUSION: In ART-naive patients, CKD is common, and low eGFR was associated with lower CD4 counts.