Early treatment with antiretroviral therapy (ART) was found to be safe for patients with HIV (PWH), according to a study published in Kidney International. 1 This finding addresses concerns that long-term exposure to nephrotoxic ART may outweigh the benefits of the drug.
Acute kidney injury and chronic kidney disease (CKD) are at increased risk in PWH due to the influence of HIV, traditional risk factors, and the potential for nephrotoxicity on ART. In the START trial, estimated glomerular filtration rate (eGFR) was found to decrease over 2 years of follow-up in patients who deferred ART or immediately received ART; after longer follow-up, he His eGFR trajectories converged in the two groups. 2 This study compares changes in eGFR in START participants after 5.5 years of follow-up and describes CKD events that occurred during 9.3 years of follow-up.
START includes participants who are not on ART treatment, diagnosed with HIV, and have a CD4 cell count <500 cells/mm3. All participants were randomly assigned to either immediate ART or deferred ART until evidence of disease progression. Participants receiving dialysis were excluded, but there were no other restrictions based on renal function. All her ART regimens were from the list of approved regimens. Data were unblinded after patients crossed the monitoring boundary and after a median follow-up of 2.8 years.
Kidney | Image credit: Crystal Light – Stock.adobe.com
The outcome for combined renal disease was renal failure or death from renal failure. The date of randomization was used as the baseline. At baseline he measured UACR and participants who had at least one follow-up visit were included in his eGFR analysis. Serum creatinine was measured at baseline and after his 1, 4, and 8 months before being measured annually. Urinary albumin and creatinine were collected at baseline and then at months 24 and 48. The annual percentage change in his eGFR from baseline between the two arms constituted his eGFR analysis. The UACR analysis compared the annual percentage change in his UACR from baseline.
Between 2009 and 2013, 4,684 participants were randomly assigned to two groups. By 2015, he was one of only three participants overall to have had a CKD event, of which he was in the ART group with two deferred. This increased to 9 CKD events in 8 participants at the end of 2021 after a median follow-up of 9.3 years (IQR, 8.5-10.4 years). Baseline eGFR for 6 of 8 participants was 60 to 90 mL/min/1.73m.2.
The eGFR analysis included 4,284 participants, median age at study entry was 36 years, and 30.4% reported their race as Black. Median baseline eGFR was 111 mL/min/1.73m.2.
The eGFR decline rate was 1.19 mL/min/1.73m2 per year over a median of 5 (IQR, 4-6) years. This rate of decline was similar in both groups. After adjusting for UACR, the difference in points between treatment groups was not significant. The annual rate of decrease in eGFR in the deferred group was 0.26 mL/min/1.73m2 (95% CI, 0.06-0.46) after adjusting for time-update variables. In participants aged 45 years and older, the annual rate of eGFR decline was 0.62 mL/min/1.73 m2 (95% CI, 0.21-1.04) faster in the delayed group compared with the immediate group. Men in the deferred group had a faster decline in eGFR compared to the immediate group, 0.39 mL/min/1.73 m2 (95% CI, 0.16-0.63).
A total of 9.8% of participants had a decrease in eGFR of 30% or more. There was no significant difference between treatment groups (incidence rate ratio) [IRR], 1.15; 95% CI, 0.95-1.38). Baseline UACR >30 mg/g increases the likelihood of a confirmed event.
This study had several limitations. Both the immediate and deferred treatment groups included participants who used drugs that affected tubular secretion of creatinine. Measurement of serum creatinine was not standardized. The 2021 CKD-EPI equation was used in this study but has not been evaluated for use in PWH. It was difficult to directly compare the incidence of progressive CKD with the previous START trial in PWH.
Researchers concluded that starting ART early is safe for PWH in terms of kidney health, as potential nephrotoxicity of ART does not outweigh the benefits of ART, such as viral suppression and immune reconstitution. I attached it.
References
Pelchen-Matthews A, Mocroft A, Ryom L, et al. Long-term effects of immediate versus deferred antiretroviral therapy on renal health in HIV-infected individuals. Nephrology Published online on April 30, 2024. doi:10.1016/j.kint.2024.04.010Achhra AC, Mocroft A, Ross M, et al. Effect of early versus deferred antiretroviral therapy on estimated glomerular filtration rate in HIV-positive individuals in the START trial. Int J Antibacterial agents. 2017 Sep;50(3):453-460. doi:10.1016/j.ijantimicag.2017.04.021
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