6/28/23, 11:35 PM INSIGHT START Pathway Feedback Search Clinical Topics Home Studies INSIGHT START INSIGHT START Disease Human immunodeficiency virus i 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 N = 4685 73.0% male 4685 patients (1257 female, 3428 male) Inclusion criteria: HIV-positive adults who had a CD4+ count > 500 cells/mm Key exclusion criteria: pregnant or breastfeeding women, prior use of ART, or any prior immunomodulatory therapy, history of any AIDS-defining condition; presence of symptoms consistent with HIV disease progression; or a history of myocardial infarction, angioplasty or bypass surgery, stroke, dialysis, renal transplantation, decompensated liver disease, or non- AIDS-defining cancer within 6 months before randomization Interventions N=2326 immediate-initiation (CD4+ count > 500 cells/mm ) N=2359 deferred-initiation (CD4+ count < 350 cells/mm or until the development of the AIDS or another condition that dictated the use of antiretroviral therapy) Primary outcome https://web.pathway.md/studies/recBrLFOMYMdZap8Z 1/2 6/28/23, 11:35 PM INSIGHT START Pathway Any serious AIDS-related event, serious non-AIDS-related event, or death 4.1 % 4.1 3.1 % 2.0 % 1.8 Significant decrease 1.0 % NNT = 43 0.0 % Immediate-initiation Deferred-initiation 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 adults who had a CD4+ count > 500 cells/mm , 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. Open reference URL https://web.pathway.md/studies/recBrLFOMYMdZap8Z 2/2