A comparison of measured and estimated glomerular filtration rate in successfully treated HIV-patients with preserved renal function.

BACKGROUND: Monitoring of renal function becomes increasingly important in the aging population of HIV-1 infected patients. We compared Cockroft & Gault (C&G), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Modification of Diet in Renal Disease (MDRD), Cystatin C- and 24 h urine-based estimated GFR (eGFR) with the gold standard, measured GFR (mGFR) using [125I]-iothalamate. METHODS: Substudy within a randomized, multinational trial comparing continuing zidovudine/ lamivudine with switching to tenofovir/ emtricitabine in patients with suppressed HIV-1 infection. Accuracy (defined as the mean difference between eGFR and mGFR) and precision (defined as standard deviation (SD) of the mean difference between eGFR and mGFR) of the eGFRs were calculated using linear regression and Bland & Altman analysis. RESULTS: We included 19 patients, 18 men, 15 Caucasian, mean (SD) age 46.0 y (± 8.9) and BMI 23.9 kg/m2 (± 3.0). Mean (SD) mGFR was 102 ml/min/1.73 m2 (± 19), 4 patients had mild renal dysfunction. All eGFRs tended to underestimate true GFR, with best accuracy for C&G (-1 ml/min/1.73 m2), CKD-EPI (-1 ml/min/1.73 m2), 24 hcreatinine clearance (-2 ml/min/1.73 m2) and MDRD-6 (0 ml/min/1.73 m2), and worst for cystatin C-based (-9 ml/min/1.73 m2) and MDRD-4 estimations (-10 ml/min/1.73 m2). Accuracy worsened at higher mGFR, but was not significantly influenced by age. C&G tended to overestimate at higher BMI. Precision was comparable for all GFR estimations. CONCLUSIONS: In this limited number of patients with preserved renal function and suppressed HIV-infection C&G and CKD-EPI appeared to be the best reflection of real GFR and most practical tool for monitoring GFR.

Pharmacokinetics and short-term efficacy of a double-boosted protease inhibitor regimen in treatment-naive HIV-1-infected adults.

OBJECTIVES: To study the pharmacokinetics and short-term efficacy of low and standard dose lopinavir/ritonavir and saquinavir combinations in Thai, human immunodeficiency virus (HIV)-infected, treatment-naive patients. METHODS: In this open-label, 24-week, prospective study, 48 treatment-naive patients were randomized to lopinavir/ritonavir 400/100 mg+saquinavir 1000 mg twice daily (arm A), lopinavir/ritonavir 400/100 mg+saquinavir 600 mg twice daily (arm B), lopinavir/ritonavir 266/66 mg+saquinavir 1000 mg twice daily (arm C), or lopinavir/ritonavir 266/66 mg+saquinavir 600 mg twice daily (arm D). A 12 h. pharmacokinetic profile in all patients was performed. Plasma concentrations of saquinavir and lopinavir were determined using an HPLC technique. HIV-1 RNA was measured over 24 weeks. RESULTS: Forty-three subjects were included in the pharmacokinetic analysis. The total exposure differed significantly for the different arms. Median values for lopinavir area under the curve at 0-12 h were 128.2, 119.2, 66.1 and 68.5 mg.h/L for arms A-D, respectively. For saquinavir, the median values were 36.9, 19.2, 25.3 and 12.4 mg.h/L for arms A-D, respectively. The proportion of patients having a viral load below 50 copies/mL at week 24 was 39% for arm A, 63% for arm B, 55.0% for arm C, and 69% for arm D. CONCLUSIONS: The pharmacokinetic parameters for the different treatment arms were adequate. However, the proportion of subjects with an undectable viral load at week 24 was lower than anticipated.

Persistent decline in estimated but not measured glomerular filtration rate on tenofovir may reflect tubular rather than glomerular toxicity.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) has been associated with proximal renal tubulopathy and reduction in estimated glomerular filtration rate (eGFR), without accounting for the tubular secretion of creatinine. METHODS: A substudy was performed among 19 participants of a randomized 48-week trial, comparing continuing first-line zidovudine/lamivudine (ZDV/3TC) with switching to TDF/emtricitabine (FTC). GFR was measured with [(125)I]-iothalamate (mGFR) and effective renal plasma flow (ERPF) with [(131)I]-hippuran. eGFR and tubular effects were assessed using plasma and urine samples. RESULTS: Of the 19 patients, 18 were men, 15 whites, mean (SD) age 46.0 (8.9) years, plasma HIV-1 RNA less than 50 copies/ml in all. After 48 weeks, eGFR using Cockcroft-Gault equation and ERPF, but not mGFR, had significantly decreased, and urinary α1-microglobulin/creatinine and microalbumin/creatinine significantly increased in patients on TDF. Although phosphate metabolism on TDF was affected at week 4, differences between groups disappeared during follow-up. CONCLUSION: Replacing ZDV/3TC with TDF/FTC in this limited sample of virologically suppressed HIV-1-infected adults was associated with mild persistent tubular but not glomerular dysfunction over 48 weeks. The observed persistent decrease in Cockcroft-Gault-based eGFR, but not mGFR, rather than being indicative of glomerular dysfunction may be explained by TDF inhibiting tubular creatinine excretion.

Transient lowering of the viral set point after temporary antiretroviral therapy of primary HIV type 1 infection.

Whether temporary antiretroviral treatment during primary HIV infection (PHI) lowers the viral set point or affects the subsequent CD4 count decline remains unclear. The objectives of this study were to analyze the clinical, viral, and immunological effects of temporary early HAART during PHI. This is a cohort study of patients with laboratory evidence of PHI. Independent predictors of early HAART and the viral set point were analyzed using multiple regression analysis. Plasma HIV-1 RNA (pVL) and CD4 trajectories were analyzed using linear mixed models. A total of 332 patients were included in the analysis. Sixty-four patients started HAART within 180 days of seroconversion. A higher baseline pVL was independently predictive of the start of early HAART (OR: 2.69/log10pVL, p = 0.001). Thirty-two patients who interrupted early HAART were compared with 250 patients who remained untreated for more than 180 days after seroconversion. Temporary early HAART was not significantly associated with a longer AIDS-free survival but did result in an initial, but transient lowering of the viral set point. The viral set point was initially 0.6 log copies/ml lower after interruption of early HAART (p < 0.001) and remained lower during 83 weeks of follow-up. No significant difference in the slopes of CD4 decline was detected between the groups. Temporary HAART in PHI is started more frequently in patients with a higher pVL and can transiently lower the viral set point compared to never treated patients.