Long-Term Benefits from Early Antiretroviral Therapy Initiation in HIV Infection

Jens D Lundgren*, Abdel G Babiker, Shweta Sharma, Birgit Grund, Andrew N Phillips, Gail Matthews, Virginia L Kan, Bitten Aagaard, Inka Abo, Beverly Alston, Alejandro Arenas-Pinto, Anchalee Avihingsanon, Sharlaa Badal-Faesen, Carlos Brites, Cate Carey, Jorge Casseb, Amanda Clarke, Simon Collins, Giulio Maria Corbelli, Sounkalo DaoEileen T Denning, Sean Emery, Nnakelu Eriobu, Eric Florence, Hansjakob Furrer, Gerd Fätkenheuer, Jan Gerstoft, Magnus Gisslén, Katharine Goodall, Keith Henry, Andrzej Horban, Jennifer Hoy, Fleur Hudson, Raja Iskandar Shah Raja Azwa, Eynat Kedem, Anthony Kelleher, Cissy Kityo, Karin Klingman, Alberto La Rosa, Nicolas Leturque, Alan R Lifson, Marcelo Losso, Joseph Lutaakome, Juan Sierra Madero, Patrick Mallon, Kamal Mansinho, Kamal Marhoum El Filali, Jean-Michel Molina, Daniel D Murray, Dorthe Raben, INSIGHT Strategic Timing of AntiRetroviral Treatment (START) study group

*Corresponding author af dette arbejde

Abstract

BACKGROUND: For people with HIV and CD4+ counts >500 cells/mm3, early initiation of antiretroviral therapy (ART) reduces serious AIDS and serious non-AIDS (SNA) risk compared with deferral of treatment until CD4+ counts are <350 cells/mm3. Whether excess risk of AIDS and SNA persists once ART is initiated for those who defer treatment is uncertain.

METHODS: The Strategic Timing of AntiRetroviral Treatment (START) trial, as previously reported, randomly assigned 4684 ART-naive HIV-positive adults with CD4+ counts .500 cells/mm3 to immediate treatment initiation after random assignment (n = 2325) or deferred treatment (n= 2359). In 2015, a 57% lower risk of the primary end point (AIDS, SNA, or death) for the immediate group was reported, and the deferred group was offered ART. This article reports the follow-up that continued to December 31, 2021. Cox proportional-hazards models were used to compare hazard ratios for the primary end point from randomization through December 31, 2015, versus January 1, 2016, through December 31, 2021.

RESULTS: Through December 31, 2015, approximately 7 months after the cutoff date from the previous report, the median CD4+ count was 648 and 460 cells/mm3 in the immediate and deferred groups, respectively, at treatment initiation. The percentage of follow-up time spent taking ART was 95% and 36% for the immediate and deferred groups, respectively, and the time-averaged CD4+ difference was 199 cells/mm3. After January 1, 2016, the percentage of follow-up time on treatment was 97.2% and 94.1% for the immediate and deferred groups, respectively, and the CD4+ count difference was 155 cells/mm3. After January 1, 2016, a total of 89 immediate and 113 deferred group participants experienced a primary end point (hazard ratio of 0.79 [95% confidence interval, 0.60 to 1.04] versus hazard ratio of 0.47 [95% confidence interval, 0.34 to 0.65; P<0.001]) before 2016 (P=0.02 for hazard ratio difference).

CONCLUSIONS: Among adults with CD4+ counts >500 cells/mm3, excess risk of AIDS and SNA associated with delaying treatment initiation was diminished after ART initiation, but persistent excess risk remained. (Funded by the National Institute of Allergy and Infectious Diseases and others.).

OriginalsprogEngelsk
TidsskriftNEJM evidence
Vol/bind2
Udgave nummer3
ISSN2766-5526
DOI
StatusUdgivet - mar. 2023

Fingeraftryk

Dyk ned i forskningsemnerne om 'Long-Term Benefits from Early Antiretroviral Therapy Initiation in HIV Infection'. Sammen danner de et unikt fingeraftryk.

Citationsformater