INSIGHT START
Trial question
What is the role of initiation of antiretroviral therapy in patients with early asymptomatic HIV infection?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
27.0% female
73.0% male
N = 4685
4685 patients (1257 female, 3428 male).
Inclusion criteria: HIV-positive adult patients who had a CD4+ count > 500 cells/mm².
Key exclusion criteria: pregnancy or lactation; prior use of ART or immunomodulatory therapy; history of any AIDS-defining condition; presence of symptoms consistent with HIV disease progression; history of MI, angioplasty, or bypass surgery; stroke; dialysis or renal transplantation; decompensated liver disease; non-AIDS-defining cancer within 6 months before randomization.
Interventions
N=2326 immediate-initiation (CD4+ count > 500 cells/mm³).
N=2359 deferred-initiation (CD4+ count < 350 cells/mm³ or until the development of the AIDS or another condition that dictated the use of antiretroviral therapy).
Primary outcome
Any serious acquired immunodeficiency syndrome-related event, serious non-acquired immunodeficiency syndrome-related event, or death
1.8%
4.1%
4.1 %
3.1 %
2.0 %
1.0 %
0.0 %
Immediate-initiation
Deferred-initiation
Significant
decrease ▼
NNT = 43
Significant decrease in any serious AIDS-related event, serious non-AIDS-related event, or death (1.8% vs. 4.1%; HR 0.43, 95% CI 0.3 to 0.62).
Secondary outcomes
Significant decrease in serious AIDS-related events (100-person yr) (0.2 vs. 0.7; HR 0.28, 95% CI 0.15 to 0.5).
Significant decrease in serious non-AIDS-related events (0.42 vs. 0.67; HR 0.61, 95% CI 0.38 to 0.97).
No significant difference in death from any cause (0.17 vs. 0.3; HR 0.58, 95% CI 0.28 to 1.17).
Safety outcomes
No significant differences in grade 4 event (HR 1.01, 95% CI 0.73-1.39, p=0.97) and unscheduled hospitalization (HR 0.91, 95% CI 0.77-1.08, p=0.28).
Conclusion
In HIV-positive adult patients who had a CD4+ count > 500 cells/mm², immediate-initiation was superior to deferred-initiation with respect to any serious AIDS-related event, serious non-AIDS-related event, or death.
Reference
INSIGHT START Study Group, Lundgren JD, Babiker AG et al. Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection. N Engl J Med. 2015 Aug 27;373(9):795-807.
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