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

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

Why START? Reflections that led to the conduct of this large long-term strategic HIV trial

Presentes no INSIGHT Strategic Timing of AntiRetroviral Treatment Study Group: Beatriz Grinsztejn; Sandra Wagner Cardoso (Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, Brasil).Submitted by Fábio Marques ([email protected]) on 2018-10-18T16:34:27Z No. of bitstreams: 1 Why START- Reflections that led_Beatriz_Grinsztejn_etal_INI_Lapclin-AIDS_2015.pdf: 229071 bytes, checksum: 8a3f0c4d53357449801497136878104e (MD5)Approved for entry into archive by Regina Costa ([email protected]) on 2018-10-18T18:08:40Z (GMT) No. of bitstreams: 1 Why START- Reflections that led_Beatriz_Grinsztejn_etal_INI_Lapclin-AIDS_2015.pdf: 229071 bytes, checksum: 8a3f0c4d53357449801497136878104e (MD5)Made available in DSpace on 2018-10-18T18:08:40Z (GMT). No. of bitstreams: 1 Why START- Reflections that led_Beatriz_Grinsztejn_etal_INI_Lapclin-AIDS_2015.pdf: 229071 bytes, checksum: 8a3f0c4d53357449801497136878104e (MD5) Previous issue date: 201

Why START? Reflections that led to the conduct of this large long-term strategic HIV trial

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Inflammation associates with impaired small arterial elasticity early in HIV disease

We estimated small arterial elasticity and used linear regression to evaluate its association with inflammatory biomarkers among antiretroviral therapy-naïve, HIV-positive patients with high CD4+ counts. After adjustment, high-sensitivity C-reactive protein and interleukin-6 were inversely associated with small arterial elasticity. These data suggest that systemic inflammation may contribute to vascular dysfunction even in very early HIV disease. © The Author(s) 2018