1 / 9

HIV Early Treatment Project Groups 1 and 2

HIV Early Treatment Project Groups 1 and 2.

hagen
Download Presentation

HIV Early Treatment Project Groups 1 and 2

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. HIV Early Treatment ProjectGroups 1 and 2 • Among HIV-infected participants in sub-Saharan Africa, does initiation of antiretroviral treatment (ART) at CD4+ counts above 500 cells/mm3 result in a reduction in all-cause mortality compared to deferral of initiation of ART until the CD4+ declines to < 350 cells/mm3?

  2. Reasons for Deferral • In high-income countries, absolute risk differences for AIDS or death are small compared with those at lower CD4+ counts (no good data for sub-Saharan Africa) • Concerns about complications of ART • Fear of waning adherence, resistance accumulation, and exhaustion of drug options • Unknown HIV status

  3. Serious Non-AIDS Outcomes in SMART Hazard Ratio (95% CI) No. of Patients with Events Rate Endpoints DC VS Major CVD, hepatic or renal disease 1041.81.1 1.7 CVD+ 79 1.30.8 1.6 Hepatic (Cirrhosis)17 0.30.2 1.4 Renal (ESRD) 11 0.20.1 4.5 NADM++ 47 0.80.5 1.4 Other non-AIDS death 51 0.90.5 1.8 Any of the above 1863.22.0 1.6 + MI (clinical or silent), stroke, surgery for CAD ++ Except non-melanoma skin Favors DC Favors VS

  4. Rate of AIDS and Non-AIDS Conditions by Current CD4 count AIDS defining illness Non-AIDS defining illness Steeper curve for AIDS than non-AIDS. Incidence per 1000 PYFU (95% CI) <50 51-100 101-200 201-350 351-500 501-700 >700 Current CD4 count (/mm3) Mocroft A et al, J Acquir Immune Defic Syndr 2010

  5. Evidence from Observational Studies for Initiating ART with CD4 > 350 • Comparison • CD4+ count strata HR for death • NA ACCORD <350 vs 350-500 1.7 (1.3 - 2.3) • 350-500 vs > 500 1.9 (1.4 – 2.8) • ART CC 251-350 vs 351-450 1.1 (0.8 - 1.6) • 351-450 vs 451-550 0.9 (0.6 - 1.4) • HIV-Causal 350 vs 500 1.0 (0.8-1.2) Kitahata MM et al, N Engl J Med 2009 When to Start Consortium, Lancet 2009. HIV Causal Collaboration, Annals Int Med, 2011

  6. Limitations of the Observational Studies • Conflicting results • Unmeasured confounders • Modeling assumptions required to adjust for measured confounders • Cohorts largely comprised of patients from resource-rich countries, none from sub Saharan Africa

  7. HPTN 052 Study • Primary endpoint (linked transmission) • 28 endpoints observed • 1 early therapy • 27 delayed therapy • HR=0.04; 0.01-0.27; p<.0001 Cohen MS, N Engl J Med 2011

  8. Strategic Timing of Antiretroviral Treatment (START) Design HIV-infected. 18 years or older, ART-naïve, and CD4+ count > 500 cells/mm3 Early ART Initiate ART immediately following randomization N=2,300 Deferred ART Group Defer ART until the CD4+ count declines to < 350 cells/mm3 or AIDS develops N=2,300 Primary Composite Endpoint: Serious AIDS, serious non-AIDS or all-cause mortality. Event Target = 213 primary events.

  9. Questions To Consider • Target population (e.g., asymptomatic, PMCT) • Definition of deferred ART (e.g., reasons for initiation apart from CD4+ count) • Large, simple trial? • ART regimen to be used - flexible or fixed? • Secondary endpoints • Transmission risk behavior assessment?

More Related