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arXiv · 2311.15410

A Comprehensive Analysis of HIV Treatment Efficacy in the ACTG 175 Trial Through Multiple-Endpoint Approaches

María Paula Cantarini·Florencia Ayelén Hernández
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Abstract

In the realm of medical research, the intricate interplay of epidemiological risk, genomic activity, adverse events, and clinical response necessitates a nuanced consideration of multiple variables. Clinical trials, designed to meticulously assess the efficacy and safety of interventions, routinely incorporate a diverse array of endpoints. While a primary endpoint is customary, supplemented by key secondary endpoints, the statistical significance is typically evaluated independently for each. To address the inherent challenges in studying multiple endpoints, diverse strategies, including composite endpoints and global testing, have been proposed. This work stands apart by focusing on the evaluation of a clinical trial, deviating from the conventional approach to underscore the efficacy of a multiple-endpoint procedure. A double-blind study was conducted to gauge the treatment efficacy in adults infected with human immunodeficiency virus type 1 (HIV-1), featuring CD4 cell counts ranging from 200 to 500 per cubic millimeter. A total of 2467 HIV-1-infected patients (43 percent without prior antiretroviral treatment) were randomly assigned to one of four daily regimens: 600 mg of zidovudine; 600 mg of zidovudine plus 400 mg of didanosine; 600 mg of zidovudine plus 2.25 mg of zalcitabine; or 400 mg of didanosine. The primary endpoint comprised a >50 percent decline in CD4 cell count, development of acquired immunodeficiency syndrome (AIDS), or death. This study sought to determine the efficacy and safety of zidovudine (AZT) versus didanosine (ddI), AZT plus ddI, and AZT plus zalcitabine (ddC) in preventing disease progression in HIV-infected patients with CD4 counts of 200-500 cells/mm3. By jointly considering all endpoints, the multiple-endpoints approach yields results of greater significance than a single-endpoint approach.

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María Paula Cantarini, Florencia Ayelén Hernández. 2023-11-26. A Comprehensive Analysis of HIV Treatment Efficacy in the ACTG 175 Trial Through Multiple-Endpoint Approaches. https://arxiv.org/abs/2311.15410

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