Lodi, S;
Sharma, S;
Lundgren, JD;
Phillips, AN;
Cole, SR;
Logan, R;
Agan, BK;
... INSIGHT Strategic Timing of AntiRetroviral Treatment study group, .; + view all
(2016)
The per-protocol effect of immediate versus deferred antiretroviral therapy initiation.
AIDS
, 30
(17)
10.1097/QAD.0000000000001243.
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Lodi et al 2016 The per-protocol effect of immediate vs. deferred ART initiation in the START.pdf Download (278kB) | Preview |
Abstract
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.
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