Kidney Function Better Over 2 Years With Immediate ART in START Trial
August 4, 2016
Starting antiretroviral therapy (ART) immediately at a high CD4 count in the international START trial -- rather than delaying therapy -- was associated with a significantly higher estimated glomerular filtration rate (eGFR) over 2.1 years of follow-up. Immediate ART was also linked to lower incidence of ≥1+ proteinuria, according to the study presented at AIDS 2016.
START randomized asymptomatic HIV-positive people to start ART immediately at a CD4 count above 500 cells/mm3 or to defer ART until the CD4 count dropped to 350 cells/mm3 or AIDS developed. After three years of follow-up, risk of AIDS, a serious non-AIDS illness or death was 57% lower in the immediate-ART group (P < .001). Because the impact of ART on renal function in people with a high CD4 count is unknown, START investigators compared eGFR changes in the immediate and deferred arms among trial participants who had a baseline eGFR and at least one follow-up eGFR during the trial.
The analysis included 2294 people in the immediate-ART arm and 2335 in the deferred arm. Median age stood at 36 years in both groups, 27% in both groups were women and 30% in both groups were black. The immediate and deferred groups also matched in baseline CD4 count (651 cells/mm3) and viral load (4.1 log10 copies/mL). Baseline median eGFR by the CKD-EPI equation measured 112 mL/min in the immediate-ART arm and 111 mL/min in the deferred arm. High proportions in the immediate and deferred arms -- 88.6% and 89.3% -- started a regimen containing tenofovir disoproxil fumarate (TDF, Viread), known for its potentially harmful impact on kidney function.
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Throughout follow-up eGFR dropped in both START arms, but the decline proved steeper in the deferred arm. After a median follow-up of 2.1 years, a random effects linear regression model adjusted for baseline eGFR and years since randomization determined that average eGFR was 0.56 mL/min higher (95% confidence interval [CI] 0.003 to 1.11) in the immediate arm, a significant difference (P = .049). Results were nearly identical in a model also adjusted for age, gender, race, proteinuria, smoking status and several other variables. In a third model adjusted for all of these variables plus current TDF or ritonavir-boosted protease inhibitor (PI) use, average eGFR was 1.72 mL/min higher (95% CI 1.11 to 2.34, P < .001) in the immediate-ART arm. The immediate-ART arm also had a 26% lower rate of ≥1+ proteinuria than the deferred arm (incidence rate ratio 0.74, 95% CI 0.55 to 1.00, P = .049).
Among black study participants, follow-up eGFR was an average 2.43 mL/min higher (95% CI 1.43 to 3.42, P < .001) in the immediate arm than the deferred arm. That difference grew after adjustment for current TDF or boosted PI use (3.90 mL/min, 95% CI 2.48 to 4.97, P < .001). In the unadjusted analysis, follow-up eGFR did not differ between the immediate and deferred arms in nonblack participants. But after adjustment for current TDF or boosted PI use, eGFR was significantly higher among nonblacks in the immediate-ART arm than in the deferred arm (1.05 mL/min, 95% CI 0.33 to 1.77, P = .004).
The START investigators concluded that their findings "illustrate the complex relationship between decreasing renal function, genetic disposition for renal decline, the use of renal toxic antiretrovirals and uncontrolled HIV."
Mark Mascolini writes about HIV infection.
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This article was provided by TheBodyPRO. It is a part of the publication The 21st International AIDS Conference (AIDS 2016).
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