AIDS_24(11)1667#1678_RCI1AL4152 - (Page 1671)

eGFR, CKD and antiretroviral drug use in HIV-positive patients Mocroft et al. 1671 4.5 5 3.5 4 2.5 3 1.5 2 0.5 1 0 0 N = 6843 6 12 6598 18 24 30 Months from baseline 5323 36 3789 42 48 2298 Fig. 1. Progression to chronic kidney disease.CKDdefined as confirmed (persisting for3 months) decrease to eGFR to 60ml/min per 1.73m2 or less if eGFR at baseline above 60ml/min per 1.73m2 or confirmed 25% decrease in eGFR if baseline eGFR 60ml/ min per 1.73m2 or less. CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate. P<0.0001]. No other antiretroviral drugs or type of cART regimen was associated with CKD. For example, after adjustment, each additional year of exposure to abacavir was associated with a 4% increased incidence of CKD (IRR 1.04, 95% CI 0.98–1.09, P¼0.16), with efavirenz was 5% (IRR 1.05, 95% CI 0.98–1.10, P¼0.12), with zidovudine was 0% (IRR 1.00, 95% CI 0.96–1.04, P¼0.97) and with stavudine was 3% (IRR 1.03, 95% CI 0.98–1.08, P¼0.28). Whenusing theMDRDformula [15], 9162 patientswere included in analyses and 277 developed CKD during 39 250.3 PYFU, an incidence of 0.95 per 100 PYFU (95% CI 0.84–1.06). Using the CKD Epidemiology Collaboration formula [34], there were 258 patients who developed CKD (incidence of 0.88 per 100 PYFU, 95% CI 0.77–0.99). Therewere 129 events (incidence of 0.60 per 100 PYFU, 95% CI 0.49–0.70) using the INSIGHT when baseline eGFR 60 ml/min per 1.73m2). In all cases, the results were completely consistent with each other (Fig. 3), as was CKD defined solely as confirmed eGFR of 60 ml/min per 1.73m2 or less when baseline eGFR above 60 ml/min per 1.73m2 (203 events). definition (confirmed 25% decline in eGFR to 60 ml/ min per 1.73m2 or confirmed 25% decline in eGFR atazanavir. Similarly, the association with atazanavir and lopinavir/r was unaffected by censoring follow-up at starting tenofovir, although the marked reduction in power (40% of follow-up timewas removed) reduced the statistical significance. Finally, the adjusted IRR for tenofovir per additional year of exposure was maintained when the analysis was censored at initiation of a boostedprotease inhibitor-containing regimen (60% of follow-up time was removed). Antiretroviral drugs are often taken together; therefore, we performed additional analyses censoring patient follow-up, using the Cockcroft–Gault formula (Fig. 3). Censoring patient follow-up at starting, atazanavir reduced the follow-up time by 19%. Figure 3 can then be interpreted as the adjusted IRR per additional year of exposure to tenofovir or lopinavir/r in patients who have not started atazanavir. The adjusted IRR per additional year of exposure to tenofovir and lopinavir/r were very similar, which suggests that the increased incidence of CKDin patients taking lopinavir/r or tenofovir cannot be explained by the fact that the patientwas also treated with In addition to assessing the effect of continuous exposure to antiretroviral drugs for their possible association with CKD, other ways of assessing the effect of antiretroviral drugs was explored, as shown in Web Fig. 1(a) (Supplemental Digital Content 1, http://links.lww.com/QAD/ A38, stratifying by years of exposure) and Web Fig. 1(b) (Supplemental Digital Content 1, http://links.lww.com/ QAD/A39, current and previous use of antiretroviral drugs). Of note, the power of these analyses is reduced compared with our main analysis. After adjustment, there was an increasing trend ofCKDassociated with increasing exposure to atazanavir or indinavir(Web Fig. 1a); therewas little additional increase in the incidence of CKD after 24 months exposure to tenofovir, whereas the increased incidence of CKD for lopinavir/r was only seen (with marginal significance) in patients with more than 36months of exposure. Patientswho had started atazanavir or lopinavir/r but were not currently taking the drug did not have an increased incidence of CKD compared with those who had never started the drug (Web Fig. 1b), whereas for indinavir and tenofovir, patients who had stopped the drug continued to have a significantly increased incidence of CKD. Thiswas further investigated for tenofovir. After adjustment, compared with patients who had never started tenofovir, those who had started tenofovir but stopped within the last 12months had a fourfold increased incidence ofCKD(adjusted IRR4.05, 95% CI 2.51–6.53, P<0.0001). Patients who had stopped for % progressed http://links.lww.com/QAD/A38 http://links.lww.com/QAD/A38 http://links.lww.com/QAD/A39 http://links.lww.com/QAD/A39

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AIDS_24(11)1667#1678_RCI1AL4152