The per-protocol effect of immediate vs. deferred ART initiation in the START randomized trial

Sara Lodi, Shweta Sharma, Jens D Lundgren, Andrew N Phillips, Stephen R Cole, Roger Logan, Brian K Agan, Abdel Babiker, Hartwig Klinker, Haitao Chu, Matthew Law, James D Neaton, Miguel A Hernán, INSIGHT Strategic Timing of AntiRetroviral Treatment (START) study group

    18 Citationer (Scopus)


    OBJECTIVE: The START trial found a lower risk of a composite clinical outcome in HIV-positive individuals assigned to immediate initiation of antiretroviral therapy (ART) compared with those assigned to deferred initiation. However, 30% of those assigned to deferred initiation started ART earlier than the protocol specified. To supplement the published intention-to-treat effect estimates, here we estimate the per-protocol effect of immediate versus deferred ART initiation in START.

    DESIGN: The START trial randomized 4685 HIV-positive participants with CD4 counts > 500 /mm to start ART immediately after randomization (immediate initiation group) or to wait until the CD4 count dropped below 350 cells/mm or an AIDS diagnosis (deferred initiation group).

    METHODS: We used the parametric g-formula to estimate and compare the cumulative 5-year risk of the composite clinical outcome in the immediate and deferred initiation groups had all the trial participants adhered to the protocol.

    RESULTS: We estimated that the 5-year risk of the composite outcome would have been 3.2% under immediate ART initiation and 7.0% under deferred initiation. The difference of 3.8% (95% confidence interval 1.5,6.5) was larger than the intention-to-treat effect estimate of 3.1%, corresponding to a difference in effect estimates of 0.72% (-0.35,2.35).

    CONCLUSIONS: The intention-to-treat effect estimate may underestimate the benefit of immediate ART initiation by 23%. This estimate can be used by patients and policy makers who need to understand the full extent of the benefit of changes in ART initiation policies.

    Udgave nummer17
    Sider (fra-til)2659-2663
    StatusUdgivet - 2016


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