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Duration of ART and Specific Antiretrovirals Tied to Hypophosphatemia and Albuminuria
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2nd International Workshop on HIV and Aging, October 27-28, 2011, Baltimore, Maryland
Mark Mascolini
One quarter of antiretroviral-treated people in the Vancouver HIV cohort has albuminuria, and hypophosphatemia developed at a rate of 6 cases per 100 person-years on antiretroviral therapy (ART) [1]. Longer treatment with atazanavir raised the risk of albuminuria, while shorter time on abacavir, emtricitabine, or zidovudine lowered the risk of hypophosphatemia.
Albuminuria and hypophosphatemia both signal poor kidney function and may result from individual antiretrovirals or duration of combination therapy. To assess prevalence and incidence of these abnormalities in antiretroviral-treated adults, researchers at Vancouver's British Columbia Centre for Excellence in HIV/AIDS analyzed both measures in adults who started ART between August 1, 1996 and August 31, 2009. Both lab values are routinely monitored in British Columbia.
The researchers defined hypophosphatemia as more than two consecutive phosphate measurements below 0.8 mmol/L with at least one of them during antiretroviral therapy. Among 499 people with phosphate measured before they started ART, 21 (4%) had mild hypophosphatemia (between 0.65 and 0.80 mmol/L) and 5 (1%) had moderate hypophosphatemia (between 0.32 and 0.65 mmol/L).
Among 473 people with normal phosphate levels when they started ART, 97 (20.5%) had confirmed hypophosphatemia during ART after a median 29.5 months of follow-up to yield an incidence of 6.0 events per 100 person-years (95% confidence interval 4.8 to 7.2). In these 473 people regression analysis for time to hypophosphatemia determined that every 10 years of age boosted the risk 34% (adjusted hazard ratio [AHR] 1.34, 95% CI 1.11 to 1.62).
Every lower 10% of total antiretroviral treatment time spent taking zidovudine, abacavir, or emtricitabine was independently associated with lower risk of hypophosphatemia:
-- Each 10% less time on zidovudine: 13% lower risk (AHR 0.87, 95% CI 0.78 to 0.99)
-- Each 10% less time on abacavir: 17% lower risk (AHR 0.83, 95% CI 0.75 to 0.91)
-- Each 10% less time on emtricitabine: 11% lower risk (AHR 0.89, 95% CI 0.83 to 0.96)
The Vancouver team defined albuminuria as a urine albumin-to-creatinine ratio above 2.0 mg/mmol for men and above 2.8 mg/mmol for women. Of 782 people studied, 161 (21%) had microalbuminuria and 25 (3%) had macroalbuminuria. Every 10 years of age raised the risk of prevalent albuminuria 37% (AHR 1.37, 95% CI 1.13 to 1.66). Every 10 mL/min higher estimated glomerular filtration rate lowered the risk of albuminuria more than 10% (AHR 0.88, 95% CI 0.80 to 0.96).
Two antiretroviral factors independently raised the risk of albuminuria: Each additional year of ART inflated the risk 8% (AHR 1.08, 95% CI 1.02 to 1.14), and each lower 10% of antiretroviral treatment time on atazanavir inflated the risk 6% (AHR 1.06, 95% CI 1.02 to 1.11).
The Vancouver investigators cautioned that longer-term implications of these findings require further study.
Reference
1. Harris M, Hull M, Yip B, et al. Hypophosphatemia and albuminuria are associated with older age in HIV+ adults receiving antiretroviral therapy (ART). 2nd International Workshop on HIV and Aging, October 27-28, 2011. Baltimore, Maryland. Abstract P_01.
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