UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

The per-protocol effect of immediate versus deferred antiretroviral therapy initiation

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. Green open access

[img]
Preview
Text
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.

Type: Article
Title: The per-protocol effect of immediate versus deferred antiretroviral therapy initiation
Open access status: An open access version is available from UCL Discovery
DOI: 10.1097/QAD.0000000000001243
Publisher version: http://dx.doi.org/10.1097/QAD.0000000000001243
Language: English
Additional information: Copyright © 2016 Wolters Kluwer Health, Inc.
Keywords: per-protocol effect, g-formula, antiretroviral treatment, HIV
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Global Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Global Health > Infection and Population Health
URI: https://discovery.ucl.ac.uk/id/eprint/1514933
Downloads since deposit
64Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item