Hematologic, Hepatic, Renal, and Lipid Monitoring After ART
Hematologic, Hepatic, Renal, and Lipid Monitoring After ART
This observational clinical cohort included antiretroviral-naive patients participating in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) who initiated a first modern cART regimen between 2000 and 2010 and had at least 1 laboratory test of any type after cART initiation. We defined modern cART as a regimen containing a ritonavir-boosted protease inhibitor (PI), nonnucleoside reverse transcriptase inhibitor (NNRTI), or integrase inhibitor plus ≥2 nucleoside/nucleotide reverse transcriptase inhibitors. Patients were excluded if their regimen included stavudine, didanosine, or unboosted PIs, or if they had an abnormal value for the laboratory test being investigated before cART initiation. CNICS is a collaboration of 8 US HIV clinical cohorts. Ethical approval was obtained for CNICS from each site's Institutional Review Board.
We analyzed hematologic, hepatic, renal, and lipid indices after cART initiation. Hematologic measures included hemoglobin, absolute neutrophil count, or platelet count. Hepatic measures included ALT or AST. We assessed creatinine and non-high-density lipoprotein (HDL) cholesterol (calculated by subtracting HDL from total cholesterol) for renal and lipid assessments, respectively. Abnormal values were defined as hematologic = hemoglobin ≤10 g/dL, neutrophil count ≤750 cells per cubic millimeter, or platelet count ≤50 × 10/L; hepatic = ALT or AST ≥3 times the upper limit of normal; renal = estimated glomerular filtration rate <50 mL·min·1.73m; and lipid = non-HDL cholesterol ≥160 mg/dL. All analyses were stratified by laboratory category.
Patients contributed time from cART initiation to the first of: switch/discontinuation of any antiretroviral for >14 days, loss-to-follow-up (>12 months without a clinic visit), last clinic visit before December 31, 2010, or 3 years post-cART initiation because <15% of patients remained. Post-cART initiation, if an abnormality occurred for the laboratory category being assessed, patient–time was censored immediately after the abnormality (eg, patient with hepatic abnormality was censored when assessing hepatic monitoring but not other laboratory indices). The initial abnormal test was counted as an event.
We calculated median time-to-first test, and the cumulative number of tests through 3, 6, 12, 18, and 24 months of cART use. Poisson regression was used to estimate overall testing rates and rates by time interval after cART initiation. Bivariable and multivariable Cox regression was used to estimate hazard ratios and 95% confidence intervals to evaluate demographic and clinical characteristics at cART initiation as predictors of time-to-first-laboratory-test. Repeated events analyses were conducted to evaluate predictors of time-to-laboratory test incorporating all tests an individual had during follow-up, using the Anderson–Gill model and a robust covariance estimator. Multivariable models included study site and all variables predictive in bivariable analysis (P < 0.10). All analyses were conducted in SAS.
Methods
This observational clinical cohort included antiretroviral-naive patients participating in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) who initiated a first modern cART regimen between 2000 and 2010 and had at least 1 laboratory test of any type after cART initiation. We defined modern cART as a regimen containing a ritonavir-boosted protease inhibitor (PI), nonnucleoside reverse transcriptase inhibitor (NNRTI), or integrase inhibitor plus ≥2 nucleoside/nucleotide reverse transcriptase inhibitors. Patients were excluded if their regimen included stavudine, didanosine, or unboosted PIs, or if they had an abnormal value for the laboratory test being investigated before cART initiation. CNICS is a collaboration of 8 US HIV clinical cohorts. Ethical approval was obtained for CNICS from each site's Institutional Review Board.
We analyzed hematologic, hepatic, renal, and lipid indices after cART initiation. Hematologic measures included hemoglobin, absolute neutrophil count, or platelet count. Hepatic measures included ALT or AST. We assessed creatinine and non-high-density lipoprotein (HDL) cholesterol (calculated by subtracting HDL from total cholesterol) for renal and lipid assessments, respectively. Abnormal values were defined as hematologic = hemoglobin ≤10 g/dL, neutrophil count ≤750 cells per cubic millimeter, or platelet count ≤50 × 10/L; hepatic = ALT or AST ≥3 times the upper limit of normal; renal = estimated glomerular filtration rate <50 mL·min·1.73m; and lipid = non-HDL cholesterol ≥160 mg/dL. All analyses were stratified by laboratory category.
Patients contributed time from cART initiation to the first of: switch/discontinuation of any antiretroviral for >14 days, loss-to-follow-up (>12 months without a clinic visit), last clinic visit before December 31, 2010, or 3 years post-cART initiation because <15% of patients remained. Post-cART initiation, if an abnormality occurred for the laboratory category being assessed, patient–time was censored immediately after the abnormality (eg, patient with hepatic abnormality was censored when assessing hepatic monitoring but not other laboratory indices). The initial abnormal test was counted as an event.
We calculated median time-to-first test, and the cumulative number of tests through 3, 6, 12, 18, and 24 months of cART use. Poisson regression was used to estimate overall testing rates and rates by time interval after cART initiation. Bivariable and multivariable Cox regression was used to estimate hazard ratios and 95% confidence intervals to evaluate demographic and clinical characteristics at cART initiation as predictors of time-to-first-laboratory-test. Repeated events analyses were conducted to evaluate predictors of time-to-laboratory test incorporating all tests an individual had during follow-up, using the Anderson–Gill model and a robust covariance estimator. Multivariable models included study site and all variables predictive in bivariable analysis (P < 0.10). All analyses were conducted in SAS.
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