The per-protocol effect of immediate versus deferred antiretroviral therapy initiation. (13th November 2016)

• Record Type: Journal Article
• Authors: Lodi, Sara; Sharma, Shweta; Lundgren, Jens D.; Phillips, Andrew N.; Cole, Stephen R.; Logan, Roger; Agan, Brian K.; Babiker, Abdel; Klinker, Hartwig; Chu, Haitao; Law, Matthew; Neaton, James D.; Hernán, Miguel A.
• Is Part Of: AIDS. Volume 30:Number 17(2016)
• Publication Date: 2016-11-13
• Subjects: antiretroviral treatment -- g-formula -- HIV -- per-protocol effect; AIDS (Disease) -- Periodicals; Acquired Immunodeficiency Syndrome; AIDS (Disease); Periodicals; Periodicals; 616.9792005
• DOI: 10.1097/QAD.0000000000001243
• Languages: English
• ISSNs: 0269-9370

Abstract

Abstract : Objective: The Strategic Timing of AntiRetroviral Treatment (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 (ITT) 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 + cell counts more than 500 cells/μl to start ART immediately after randomization (immediate initiation group) or to wait until the CD4 + cell count dropped below 350 cells/μl 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 initiation group, 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 ITT effect estimate of 3.1%, corresponding to a difference in effect estimates of 0.72% (−0.35, 2.35). Conclusion: The ITT 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. Abstract : Supplemental Digital Content is available in the text