TY - JOUR
T1 - Long-Term Benefits from Early Antiretroviral Therapy Initiation in HIV Infection
AU - Lundgren, Jens D
AU - Babiker, Abdel G
AU - Sharma, Shweta
AU - Grund, Birgit
AU - Phillips, Andrew N
AU - Matthews, Gail
AU - Kan, Virginia L
AU - Aagaard, Bitten
AU - Abo, Inka
AU - Alston, Beverly
AU - Arenas-Pinto, Alejandro
AU - Avihingsanon, Anchalee
AU - Badal-Faesen, Sharlaa
AU - Brites, Carlos
AU - Carey, Cate
AU - Casseb, Jorge
AU - Clarke, Amanda
AU - Collins, Simon
AU - Corbelli, Giulio Maria
AU - Dao, Sounkalo
AU - Denning, Eileen T
AU - Emery, Sean
AU - Eriobu, Nnakelu
AU - Florence, Eric
AU - Furrer, Hansjakob
AU - Fätkenheuer, Gerd
AU - Gerstoft, Jan
AU - Gisslén, Magnus
AU - Goodall, Katharine
AU - Henry, Keith
AU - Horban, Andrzej
AU - Hoy, Jennifer
AU - Hudson, Fleur
AU - Azwa, Raja Iskandar Shah Raja
AU - Kedem, Eynat
AU - Kelleher, Anthony
AU - Kityo, Cissy
AU - Klingman, Karin
AU - Rosa, Alberto La
AU - Leturque, Nicolas
AU - Lifson, Alan R
AU - Losso, Marcelo
AU - Lutaakome, Joseph
AU - Madero, Juan Sierra
AU - Mallon, Patrick
AU - Mansinho, Kamal
AU - Filali, Kamal Marhoum El
AU - Molina, Jean-Michel
AU - Murray, Daniel D
AU - Raben, Dorthe
AU - INSIGHT Strategic Timing of AntiRetroviral Treatment (START) study group
PY - 2023/3
Y1 - 2023/3
N2 - 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.).
AB - 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.).
U2 - 10.1056/evidoa2200302
DO - 10.1056/evidoa2200302
M3 - Journal article
C2 - 37213438
SN - 2766-5526
VL - 2
JO - NEJM evidence
JF - NEJM evidence
IS - 3
ER -