Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection

Jens D Lundgren, Abdel G Babiker, Fred Gordin, Sean Emery, Birgit Grund, Shweta Sharma, Anchalee Avihingsanon, David A Cooper, Gerd Fätkenheuer, Josep M Llibre, Jean-Michel Molina, Paula Munderi, Mauro Schechter, Robin Wood, Karin L Klingman, Simon Collins, H Clifford Lane, Andrew N Phillips, James D Neaton, INSIGHT START Study GroupCourt Pedersen

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

BACKGROUND: Data from randomized trials are lacking on the benefits and risks of initiating antiretroviral therapy in patients with asymptomatic human immunodeficiency virus (HIV) infection who have a CD4+ count of more than 350 cells per cubic millimeter.

METHODS: We randomly assigned HIV-positive adults who had a CD4+ count of more than 500 cells per cubic millimeter to start antiretroviral therapy immediately (immediate-initiation group) or to defer it until the CD4+ count decreased to 350 cells per cubic millimeter or until the development of the acquired immunodeficiency syndrome (AIDS) or another condition that dictated the use of antiretroviral therapy (deferred-initiation group). The primary composite end point was any serious AIDS-related event, serious non-AIDS-related event, or death from any cause.

RESULTS: A total of 4685 patients were followed for a mean of 3.0 years. At study entry, the median HIV viral load was 12,759 copies per milliliter, and the median CD4+ count was 651 cells per cubic millimeter. On May 15, 2015, on the basis of an interim analysis, the data and safety monitoring board determined that the study question had been answered and recommended that patients in the deferred-initiation group be offered antiretroviral therapy. The primary end point occurred in 42 patients in the immediate-initiation group (1.8%; 0.60 events per 100 person-years), as compared with 96 patients in the deferred-initiation group (4.1%; 1.38 events per 100 person-years), for a hazard ratio of 0.43 (95% confidence interval [CI], 0.30 to 0.62; P<0.001). Hazard ratios for serious AIDS-related and serious non-AIDS-related events were 0.28 (95% CI, 0.15 to 0.50; P<0.001) and 0.61 (95% CI, 0.38 to 0.97; P=0.04), respectively. More than two thirds of the primary end points (68%) occurred in patients with a CD4+ count of more than 500 cells per cubic millimeter. The risks of a grade 4 event were similar in the two groups, as were the risks of unscheduled hospital admissions.

CONCLUSIONS: The initiation of antiretroviral therapy in HIV-positive adults with a CD4+ count of more than 500 cells per cubic millimeter provided net benefits over starting such therapy in patients after the CD4+ count had declined to 350 cells per cubic millimeter. (Funded by the National Institute of Allergy and Infectious Diseases and others; START ClinicalTrials.gov number, NCT00867048.).

OriginalsprogEngelsk
TidsskriftThe New England Journal of Medicine
Vol/bind373
Udgave nummer9
Sider (fra-til)795-807
Antal sider13
ISSN0028-4793
DOI
StatusUdgivet - 27. aug. 2015

Fingeraftryk

Virus Diseases
HIV
Acquired Immunodeficiency Syndrome
Confidence Intervals
Clinical Trials Data Monitoring Committees
Viral Load
Cause of Death

Emneord

  • Adult
  • Anti-Retroviral Agents
  • Asymptomatic Diseases
  • CD4 Lymphocyte Count
  • Female
  • Follow-Up Studies
  • HIV
  • HIV Seropositivity
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • RNA, Viral
  • Time-to-Treatment
  • Viral Load

Citer dette

Lundgren, Jens D ; Babiker, Abdel G ; Gordin, Fred ; Emery, Sean ; Grund, Birgit ; Sharma, Shweta ; Avihingsanon, Anchalee ; Cooper, David A ; Fätkenheuer, Gerd ; Llibre, Josep M ; Molina, Jean-Michel ; Munderi, Paula ; Schechter, Mauro ; Wood, Robin ; Klingman, Karin L ; Collins, Simon ; Lane, H Clifford ; Phillips, Andrew N ; Neaton, James D ; INSIGHT START Study Group ; Pedersen, Court. / Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection. I: The New England Journal of Medicine. 2015 ; Bind 373, Nr. 9. s. 795-807.
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title = "Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection",
abstract = "BACKGROUND: Data from randomized trials are lacking on the benefits and risks of initiating antiretroviral therapy in patients with asymptomatic human immunodeficiency virus (HIV) infection who have a CD4+ count of more than 350 cells per cubic millimeter.METHODS: We randomly assigned HIV-positive adults who had a CD4+ count of more than 500 cells per cubic millimeter to start antiretroviral therapy immediately (immediate-initiation group) or to defer it until the CD4+ count decreased to 350 cells per cubic millimeter or until the development of the acquired immunodeficiency syndrome (AIDS) or another condition that dictated the use of antiretroviral therapy (deferred-initiation group). The primary composite end point was any serious AIDS-related event, serious non-AIDS-related event, or death from any cause.RESULTS: A total of 4685 patients were followed for a mean of 3.0 years. At study entry, the median HIV viral load was 12,759 copies per milliliter, and the median CD4+ count was 651 cells per cubic millimeter. On May 15, 2015, on the basis of an interim analysis, the data and safety monitoring board determined that the study question had been answered and recommended that patients in the deferred-initiation group be offered antiretroviral therapy. The primary end point occurred in 42 patients in the immediate-initiation group (1.8{\%}; 0.60 events per 100 person-years), as compared with 96 patients in the deferred-initiation group (4.1{\%}; 1.38 events per 100 person-years), for a hazard ratio of 0.43 (95{\%} confidence interval [CI], 0.30 to 0.62; P<0.001). Hazard ratios for serious AIDS-related and serious non-AIDS-related events were 0.28 (95{\%} CI, 0.15 to 0.50; P<0.001) and 0.61 (95{\%} CI, 0.38 to 0.97; P=0.04), respectively. More than two thirds of the primary end points (68{\%}) occurred in patients with a CD4+ count of more than 500 cells per cubic millimeter. The risks of a grade 4 event were similar in the two groups, as were the risks of unscheduled hospital admissions.CONCLUSIONS: The initiation of antiretroviral therapy in HIV-positive adults with a CD4+ count of more than 500 cells per cubic millimeter provided net benefits over starting such therapy in patients after the CD4+ count had declined to 350 cells per cubic millimeter. (Funded by the National Institute of Allergy and Infectious Diseases and others; START ClinicalTrials.gov number, NCT00867048.).",
keywords = "Adult, Anti-Retroviral Agents, Asymptomatic Diseases, CD4 Lymphocyte Count, Female, Follow-Up Studies, HIV, HIV Seropositivity, Humans, Kaplan-Meier Estimate, Male, RNA, Viral, Time-to-Treatment, Viral Load",
author = "Lundgren, {Jens D} and Babiker, {Abdel G} and Fred Gordin and Sean Emery and Birgit Grund and Shweta Sharma and Anchalee Avihingsanon and Cooper, {David A} and Gerd F{\"a}tkenheuer and Llibre, {Josep M} and Jean-Michel Molina and Paula Munderi and Mauro Schechter and Robin Wood and Klingman, {Karin L} and Simon Collins and Lane, {H Clifford} and Phillips, {Andrew N} and Neaton, {James D} and {INSIGHT START Study Group} and Court Pedersen",
year = "2015",
month = "8",
day = "27",
doi = "10.1056/NEJMoa1506816",
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Lundgren, JD, Babiker, AG, Gordin, F, Emery, S, Grund, B, Sharma, S, Avihingsanon, A, Cooper, DA, Fätkenheuer, G, Llibre, JM, Molina, J-M, Munderi, P, Schechter, M, Wood, R, Klingman, KL, Collins, S, Lane, HC, Phillips, AN, Neaton, JD, INSIGHT START Study Group & Pedersen, C 2015, 'Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection', The New England Journal of Medicine, bind 373, nr. 9, s. 795-807. https://doi.org/10.1056/NEJMoa1506816

Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection. / Lundgren, Jens D; Babiker, Abdel G; Gordin, Fred; Emery, Sean; Grund, Birgit; Sharma, Shweta; Avihingsanon, Anchalee; Cooper, David A; Fätkenheuer, Gerd; Llibre, Josep M; Molina, Jean-Michel; Munderi, Paula; Schechter, Mauro; Wood, Robin; Klingman, Karin L; Collins, Simon; Lane, H Clifford; Phillips, Andrew N; Neaton, James D; INSIGHT START Study Group ; Pedersen, Court.

I: The New England Journal of Medicine, Bind 373, Nr. 9, 27.08.2015, s. 795-807.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection

AU - Lundgren, Jens D

AU - Babiker, Abdel G

AU - Gordin, Fred

AU - Emery, Sean

AU - Grund, Birgit

AU - Sharma, Shweta

AU - Avihingsanon, Anchalee

AU - Cooper, David A

AU - Fätkenheuer, Gerd

AU - Llibre, Josep M

AU - Molina, Jean-Michel

AU - Munderi, Paula

AU - Schechter, Mauro

AU - Wood, Robin

AU - Klingman, Karin L

AU - Collins, Simon

AU - Lane, H Clifford

AU - Phillips, Andrew N

AU - Neaton, James D

AU - INSIGHT START Study Group

AU - Pedersen, Court

PY - 2015/8/27

Y1 - 2015/8/27

N2 - BACKGROUND: Data from randomized trials are lacking on the benefits and risks of initiating antiretroviral therapy in patients with asymptomatic human immunodeficiency virus (HIV) infection who have a CD4+ count of more than 350 cells per cubic millimeter.METHODS: We randomly assigned HIV-positive adults who had a CD4+ count of more than 500 cells per cubic millimeter to start antiretroviral therapy immediately (immediate-initiation group) or to defer it until the CD4+ count decreased to 350 cells per cubic millimeter or until the development of the acquired immunodeficiency syndrome (AIDS) or another condition that dictated the use of antiretroviral therapy (deferred-initiation group). The primary composite end point was any serious AIDS-related event, serious non-AIDS-related event, or death from any cause.RESULTS: A total of 4685 patients were followed for a mean of 3.0 years. At study entry, the median HIV viral load was 12,759 copies per milliliter, and the median CD4+ count was 651 cells per cubic millimeter. On May 15, 2015, on the basis of an interim analysis, the data and safety monitoring board determined that the study question had been answered and recommended that patients in the deferred-initiation group be offered antiretroviral therapy. The primary end point occurred in 42 patients in the immediate-initiation group (1.8%; 0.60 events per 100 person-years), as compared with 96 patients in the deferred-initiation group (4.1%; 1.38 events per 100 person-years), for a hazard ratio of 0.43 (95% confidence interval [CI], 0.30 to 0.62; P<0.001). Hazard ratios for serious AIDS-related and serious non-AIDS-related events were 0.28 (95% CI, 0.15 to 0.50; P<0.001) and 0.61 (95% CI, 0.38 to 0.97; P=0.04), respectively. More than two thirds of the primary end points (68%) occurred in patients with a CD4+ count of more than 500 cells per cubic millimeter. The risks of a grade 4 event were similar in the two groups, as were the risks of unscheduled hospital admissions.CONCLUSIONS: The initiation of antiretroviral therapy in HIV-positive adults with a CD4+ count of more than 500 cells per cubic millimeter provided net benefits over starting such therapy in patients after the CD4+ count had declined to 350 cells per cubic millimeter. (Funded by the National Institute of Allergy and Infectious Diseases and others; START ClinicalTrials.gov number, NCT00867048.).

AB - BACKGROUND: Data from randomized trials are lacking on the benefits and risks of initiating antiretroviral therapy in patients with asymptomatic human immunodeficiency virus (HIV) infection who have a CD4+ count of more than 350 cells per cubic millimeter.METHODS: We randomly assigned HIV-positive adults who had a CD4+ count of more than 500 cells per cubic millimeter to start antiretroviral therapy immediately (immediate-initiation group) or to defer it until the CD4+ count decreased to 350 cells per cubic millimeter or until the development of the acquired immunodeficiency syndrome (AIDS) or another condition that dictated the use of antiretroviral therapy (deferred-initiation group). The primary composite end point was any serious AIDS-related event, serious non-AIDS-related event, or death from any cause.RESULTS: A total of 4685 patients were followed for a mean of 3.0 years. At study entry, the median HIV viral load was 12,759 copies per milliliter, and the median CD4+ count was 651 cells per cubic millimeter. On May 15, 2015, on the basis of an interim analysis, the data and safety monitoring board determined that the study question had been answered and recommended that patients in the deferred-initiation group be offered antiretroviral therapy. The primary end point occurred in 42 patients in the immediate-initiation group (1.8%; 0.60 events per 100 person-years), as compared with 96 patients in the deferred-initiation group (4.1%; 1.38 events per 100 person-years), for a hazard ratio of 0.43 (95% confidence interval [CI], 0.30 to 0.62; P<0.001). Hazard ratios for serious AIDS-related and serious non-AIDS-related events were 0.28 (95% CI, 0.15 to 0.50; P<0.001) and 0.61 (95% CI, 0.38 to 0.97; P=0.04), respectively. More than two thirds of the primary end points (68%) occurred in patients with a CD4+ count of more than 500 cells per cubic millimeter. The risks of a grade 4 event were similar in the two groups, as were the risks of unscheduled hospital admissions.CONCLUSIONS: The initiation of antiretroviral therapy in HIV-positive adults with a CD4+ count of more than 500 cells per cubic millimeter provided net benefits over starting such therapy in patients after the CD4+ count had declined to 350 cells per cubic millimeter. (Funded by the National Institute of Allergy and Infectious Diseases and others; START ClinicalTrials.gov number, NCT00867048.).

KW - Adult

KW - Anti-Retroviral Agents

KW - Asymptomatic Diseases

KW - CD4 Lymphocyte Count

KW - Female

KW - Follow-Up Studies

KW - HIV

KW - HIV Seropositivity

KW - Humans

KW - Kaplan-Meier Estimate

KW - Male

KW - RNA, Viral

KW - Time-to-Treatment

KW - Viral Load

U2 - 10.1056/NEJMoa1506816

DO - 10.1056/NEJMoa1506816

M3 - Journal article

C2 - 26192873

VL - 373

SP - 795

EP - 807

JO - The New England Journal of Medicine

JF - The New England Journal of Medicine

SN - 0028-4793

IS - 9

ER -

Lundgren JD, Babiker AG, Gordin F, Emery S, Grund B, Sharma S et al. Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection. The New England Journal of Medicine. 2015 aug 27;373(9):795-807. https://doi.org/10.1056/NEJMoa1506816