The Effect of Interrupted/Deferred Antiretroviral Therapy on Disease Risk: A SMART and START Combined Analysis

Álvaro H. Borges, Jacqueline A Nordwall, Shweta S Mistry, Jim Neaton, Keith Henry, Olga Anagnostou, Teresa Staub, Sean Emery, Jens D. Lundgren

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Background Pooled data from the SMART and START trials were used to compare deferred/intermittent versus immediate/continuous antiretroviral therapy (ART) on disease risk. Methods Endpoints assessed were AIDS, serious non-AIDS (SNA), cardiovascular disease (CVD), cancer, and death. Pooled (stratified by study) hazard ratios (HRs) from Cox models were obtained for deferred/intermittent ART versus immediate/continuous ART; analyses were conducted to assess consistency of HRs across baseline-defined subgroups. Results Among 10156 participants, there were 124 AIDS, 247 SNA, 117 cancers, 103 CVD, and 120 deaths. Interventions in each trial led to similar differences in CD4 count and viral suppression. Pooled HRs (95% confidence interval) of deferred/intermittent ART versus immediate/continuous ART were for AIDS 3.63 (2.37-5.56); SNA 1.62 (1.25-2.09); CVD 1.59 (1.07-2.37); cancer 1.93 (1.32-2.83); and death 1.80 (1.24-2.61). Underlying risk was greater in SMART than START. Given the similar HRs for each trial, absolute risk differences between treatment groups were greater in SMART than START. Pooled HRs were similar across subgroups. Conclusions Treatment group differences in CD4 count and viral suppression were similar in SMART and START. Likely as a consequence, relative differences in risk of AIDS and SNA between immediate/continuous ART and deferred/intermittent ART were similar. Clinical Trials Registration NCT00027352 and NCT00867048.

Original languageEnglish (US)
Pages (from-to)254-263
Number of pages10
JournalJournal of Infectious Diseases
Volume219
Issue number2
DOIs
StatePublished - Jan 7 2019

Bibliographical note

Funding Information:
Disclaimer. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of this manuscript. Financial support. This work was supported by National Institutes of Health (grant numbers U01AI068641, U01AI042170, and U01AI46362 [SMART]; UM1-AI068641 and UM1-AI120197 [START]). START was supported by the National Institute of Allergy and Infectious Diseases (United States), Agence Nationale de Recherches sur le SIDA et les Hipatites Virales (France), National Health and Medical Research Council (Australia), Danish National Research Foundation (Denmark), Bundes ministerium für Bildung und Forschung (Germany), European AIDS Treatment Network, Medical Research Council (United Kingdom), National Institute for Health Research, National Health Service (United Kingdom), and the University of Minnesota. Antiretroviral drugs were donated to the central drug repository by AbbVie, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline/ ViiV Healthcare, Janssen Scientific Affairs, and Merck. The present study was also supported by the Research Council at Rigshospitalet, Danish National Research Foundation (grant number DNRF126), and Lundbeckfonden (grant number R219-2016-762 to A. H. B.). Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Keywords

  • AIDS
  • HIV
  • antiretroviral therapy
  • cancer
  • cardiovascular disease

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