CROI 2016 Abstract eBook

Abstract Listing

Poster Abstracts

474

Effect of Immediate ART on Risk of Severe Bacterial Infections: The START Trial Jemma L. O’Connor 1 ; Fred Gordin 2 ; Andrew N. Phillips 1 ; Brian Angus 3 ; David Cooper 4 ; Beatriz Grinsztejn 5 ; Gustavo Lopardo 6 ; Satyajit Das 7 ; AimeeWilkin 8 ; Jens D. Lundgren 9 ; for the INSIGHT START Study Group 1 Univ Coll London, London, UK; 2 VA Med Cntr, Washington, DC, USA; 3 John Radcliffe Hosp, Oxford, UK; 4 Kirby Inst, Sydney, Australia; 5 Inst de Pesquisa Clínica Evandro Chagas (IPEC)/Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, Brazil; 6 La Fundación del Centro de Estudios Infectológicos, Buenos Aires, Argentina; 7 Coventry and Warwickshire NHS Partnership Trust, Coventry, UK; 8 Wake Forest Univ, Winston Salem, NC, USA; 9 Rigshospitalet, Univ of Copenhagen, Copenhagen, Denmark Background: The START trial conducted amongst HIV+ people with CD4 count >500/mm 3 showed that risk of bacterial infectious disorder (BID) was reduced in those randomized to immediate ART compared with those randomized to defer ART until CD4 count <350/mm 3 . We expand on this finding by including additional bacterial infection events and we investigate whether the effect is due to the increase in CD4 and neutrophil counts that occurred in the immediate ART arm. Methods: All START participants were included in analyses. Cox proportional hazards regression was used to model the time to serious bacterial infection (SBI). SBI was defined as a composite of bacterial pneumonia (BP) (confirmed by the endpoint review committee) or any BID (as reported in the START paper) which satisfied at least one of the following three criteria: grade 4 severity, requiring unscheduled hospitalisations or causing death. We estimated the effect of randomized assignment, on the risk of SBI. We considered two models: model (i) single factors adjusted for age and sex; model (ii) multivariable adjustment for all factors (See Table 1). Models were stratified by geographic region. Results: Of 4,685 participants included in analyses 94 experienced at least one SBI during a median follow-up of 2.8 years. The median baseline neutrophil count (interquartile range) was 2810.0/mm 3 (2176.2, 3678.2). Latest average neutrophil count over follow-up was 231/mm 3 higher, and latest average CD4 count was 194/mm 3 higher, in the immediate ART arm (p<.0001). Immediate ART was associated with a reduced risk of SBI [Hazard Ratio (HR), 0.42; 95% CI, 0.27-0.65, p=0.0001; consistent for two main components of SBI (BID HR=0.38, BP HR=0.42)] in model (i), but not after adjustment for time-updated factors in model (ii) [HR, 0.72; 95% CI, 0.41-1.27,p=0.25]. Higher latest BMI [HR per 5kg/m 2 , 1.33; 95% CI, 1.11–1.59, p=0.0017] was associated with an increased risk of SBI. Higher latest CD4 count [HR per 100 cells/mm 3 , 0.83; 95% CI, 0.74–0.92, p=0.0006] was associated with a reduced risk of SBI. Latest neutrophil count was not associated with SBI [HR per 100 cells/mm 3 , 0.90; 95% CI, 0.19–4.16, p=0.89]. Conclusions: Immediate ART reduces the risk of SBI among HIV+ persons with high CD4 count and normal neutrophil count. This benefit is partly explained by ART-induced increases in CD4 count but not by increases in neutrophil count. Our study demonstrates the protective effect of immediate ART in reducing the risk of a broad spectrum of serious infections.

Poster Abstracts

475 Increased Quality of LifeWith Immediate ART Initiation: Results From the START Trial Alan Lifson ; Birgit Grund; for the INSIGHT START Quality of Life Study Group Univ of Minnesota, Minneapolis, MN, USA

Background: With HIV managed as a chronic illness, quality of life (QOL) is one important outcome in assessing HIV treatment strategies. Development of HIV-related illnesses or medication side effects can both affect QOL. The Strategic Timing of Antiretroviral Therapy (START) study randomized antiretroviral therapy (ART) naive participants with CD4 counts >500 cells/mm3 to starting ART immediately vs. deferring ART until CD4 counts declined to 350 cells or clinical disease required ART. We compared immediate vs. deferred ART groups for changes in QOL. Methods: At baseline, Month 4, 12 and then annually, participants completed a visual analogue scale (VAS) for self-assessment of overall current health and the Short-Form 12-Item Health Survey version 2 (SF-12v2) with 4 week recall. We computed three QOL outcomes from SF-12v2: (1) General health perception (GHP); (2) Physical component summary (PCS), and (3) Mental component summary (MCS). All QOL outcomes are scaled 0-100 (higher score=better QOL). PCS and MCS scores are standardized to a mean=50 in a U.S. reference population. We compared immediate and deferred ART groups for QOL changes from baseline using longitudinal mixed models adjusted for visit and baseline QOL. Results: Of 4684 START participants, 4561 had both baseline and follow-up QOL data: median baseline CD4=651 cells, median age=36 years, 27%were female, and 46% from high-income countries. Mean QOL baseline scores (with standard deviation) were VAS=80.9 (15.7), GHP=72.5 (21.5), PCS=53.7 (7.2), MCS=48.2 (10.5). Mean follow-up time was 2.6 years. The immediate group spent 95% of follow-up time on ART vs. 28% for the deferred group. Throughout follow-up, all changes in QOL favored the immediate group;

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