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Interrupted Antiretrovirals Raise Chronic Kidney Disease Risk 50% in SMART
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18th Conference on Retroviruses and Opportunistic Infections, February 27-March 2, 2011, Boston
Mark Mascolini
People who interrupted their antiretroviral therapy during the SMART trial had a 50% higher risk of chronic kidney disease (CKD) than people who stayed on steady therapy [1]. Black study participants did not run a higher risk of CKD than whites, but they had a higher risk of end-stage renal disease or death.
An earlier SMART analysis suggested that treatment interruption raises the risk of declining kidney function, indicated by higher levels of cystatin C, but creatinine-based measures did not differ between the interruption group and the steady-therapy group through the first 12 months of follow-up [2]. The new analysis aimed to determine whether treatment interruption is associated with new or progressive CKD and to identify risk factors.
This study included 2114 people who interrupted therapy based on CD4 count and 2103 people who stayed on continuous therapy through the end of follow-up in July 2007. The SMART team recorded new or progressive CKD events that reflect significant loss of kidney function, defined as at least a 25% decline in estimated glomerular filtration rate (eGFR) if baseline eGFR was 60 mL/min/1.73m(2) or less, or at least a 25% drop in eGFR to below 60 if the baseline eGFR lay above 60.
The interruption group had 1.8 CKD events per 100 person-years, compared with 1.2 per 100 person-years in the steady-therapy arm. Those rates translated into a 50% higher risk of CKD in treatment interrupters (hazard ratio [HR] 1.5, 95% confidence interval [CI] 1.1 to 2.1, P = 0.01). Cumulative estimates of progression at 12, 24, and 36 months were 1.6%, 3.4%, and 5.4% in the antiretroviral interruption arm and 0.8%, 2.2%, and 3.4% in people on continuous therapy. Higher progression risk in interrupters was greatest in the first year of follow-up (HR 2.1, 95% CI 1.2 to 3.9, P = 0.01) and was not significant with continued follow-up (HR 1.3, 95% CI 0.8 to 1.9, P = 0.24).
Several factors independently predicted shorter time to a CKD endpoint, at the following hazard ratios (and 95% CI):
-- Off treatment versus on with a viral load below 400 copies: HR 2.42 (1.08 to 5.38), P = 0.030
-- Every 10 years of age: HR 1.91 (1.38 to 2.65), P < 0.001
-- Hepatitis coinfection: HR 1.92 (1.00 to 3.68), P = 0.049
-- Diabetes: HR 2.50 (1.26 to 4.97), P = 0.009
-- Hypertension: HR 2.41 (1.31 to 4.46), P = 0.005
Next the SMART investigators compared baseline traits in trial participants who did or did not progress to end-stage renal disease or renal death during follow-up. Predictive variables were black race (P < 0.001), older age (P < 0.001), HCV coinfection (P < 0.001), diabetes (P < 0.001), hypertension (P < 0.001), prior cardiovascular disease (P = 0.003), higher low-density lipoprotein cholesterol (P = 0.002), lower high-density lipoprotein cholesterol (P = 0.01), higher body mass index (P = 0.04), lower eGFR (P < 0.001), and eGFR below 60 (P < 0.001).
The investigators cautioned that the low number of progression cases or death (18) may have affected these associations. However, 13 of the 18 people (72%) who had progressive renal disease or died of kidney failure were black. This robust association, the SMART researchers observed, reflects recent findings that black race is a strong risk factor for end-stage renal disease but not for CKD incidence in people with HIV [3]. The investigators added that only further research can determine whether changing modifiable risk factors will lower the risk of progressive kidney disease in people with HIV.
References
1. Neuhaus J, Mocroft A, Wyatt C, Ross M, INSIGHT SMART Study Group. Predictors of chronic kidney disease: SMART trial. 18th Conference on Retroviruses and Opportunistic Infections. February 27-March 2, 2011. Boston. Abstract 837.
2. Mocroft A, Wyatt C, Szczech L, et al. Interruption of antiretroviral therapy is associated with increased plasma cystatin C. AIDS. 2009;23:71-82.
3. Lucas GM, Lau B, Atta MG, Fine DM, Keruly J, Moore RD. Chronic kidney disease incidence, and progression to end-stage renal disease, in HIV-infected individuals: a tale of two races. J Infect Dis. 2008;197:1548-1557.
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