Impact of early versus deferred antiretroviral therapy on estimated glomerular filtration rate in HIV-positive individuals in the START trial. International Journal of Antimicrobial Agents
The START trial is a randomised controlled clinical trial of immediate initiation of antiretroviral therapy (ART) (‘immediate’ arm) versus deferral of ART initiation until CD4+ counts decline to <350 cells/mm3 or clinical symptoms develop (‘deferred’ arm) among participants naïve to ART with CD4+ counts >500 cells/mm3.
In this study, Achhra et al. on behalf of the INSIGHT START Study Group aimed to assess the effect of early ART upon kidney function among persons with relative immune preservation and low risk for acquired immune deficiency syndrome (AIDS) complications. Serum creatinine and urine dipstick protein were longitudinally measured and the two arms were compared for changes in eGFR (mL/min/1.73m2).
Of 4’685 START participants, 4’629 (2’294 in immediate and 2’335 deferred arm) were included. Median baseline CD4+ and eGFR were 651 and 111.5, respectively. ART was initiated in 99.0% in the immediate and 48.3% in the deferred arm, accounting for >94% and >19% of follow-up time, respectively. Overall, 89% started ART using a tenofovir-based regimen. Over 2.1 years median follow-up, mean eGFR was 0.56 higher in the immediate versus deferred arm, which was more prominent after adjustment for current tenofovir or boosted protease inhibitor use (1.85) and in Black participants (3.90) versus non-Blacks (1.05). Relative risk for proteinuria in the immediate versus deferred arm was 0.74.
In summary, this study suggests modest short-term benefit on kidney function from the immediate initiation of ART in HIV-positive individuals with high CD4+ cell count. This benefit was especially prominent in individuals of Black race and in the absence of tenofovir or boosted protease inhibitor use.