Abstract
Background. The SMART study randomized 5472 human immunodeficiency virus (HIV)-infected patients with CD4+ cell counts >350 cells/μL to intermittent antiretroviral therapy (ART; the drug conservation [DC] group) versus continuous ART (the viral supression [VS] group). In the DC group, participants started ART when the CD4+ cell count was <250 cells/μL. Clinical outcomes in participants not receiving ART at entry inform the early use of ART. Methods. Patients who were either ART naive (n = 249) or who had not been receiving ART for ≤6 months (n = 228) were analyzed. The following clinical outcomes were assessed: (i) opportunistic disease (OD) or death from any cause (OD/death); (ii) OD (fatal or nonfatal); (iii) serious non-AIDS events (cardiovascular, renal, and hepatic disease plus non-AIDS-defining cancers) and non-OD deaths; and (iv) the composite of outcomes (ii) and (iii). Results. A total of 477 participants (228 in the DC group and 249 in the VS group) were followed (mean, 18 months). For outcome (iv), 21 and 6 events occurred in the DC (7 in ART-naive participants and 14 in those who had not received ART for ≤6 months) and VS (2 in ART-naive participants and 4 in those who had not received ART for ≤6 months) groups, respectively. Hazard ratios for DC vs. VS by outcome category were as follows: outcome (i), 3.47 (95% confidence interval [CI], 1.26-9.56; P = .02); outcome (ii), 3.26 (95% CI, 1.04-10.25; P = .04); outcome (iii), 7.02 (95% CI, 1.57-31.38; P = .01); and outcome (iv), 4.19 (95% CI, 1.69-10.39; P = .002). Conclusions. Initiation of ART at CD4+ cell counts >350 cells/μL compared with <250 cells/μL may reduce both OD and serious non-AIDS events. These findings require validation in a large, randomized clinical trial. Trial registration. ClinicalTrials.gov identifier: NCT00027352.
| Original language | English |
|---|---|
| Pages (from-to) | 1133-1144 |
| Number of pages | 12 |
| Journal | Journal of Infectious Diseases |
| Volume | 197 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - 15 Apr 2008 |
Bibliographical note
Funding Information:Potential conflicts of interest. S.E. has received honoraria, consultancies, and research grants from Abbott, Boehringer In-gelheim (BI), Bristol-Myers Squibb (BMS), Chiron, Gilead Sciences, GlaxoSmithKline (GSK), Merck Sharp and Dohme, Roche, Sanofi-Aventis, Tibotec, and Virax Holdings and reports no stock or stock option holdings; A.N.P. has received honoraria, consultancies, and research grants from Roche, BMS, GSK, BI, Gilead, Tibotec, and Oxxon Therapeutics and reports no stock or stock option holdings; A.B. has received honoraria, con- sultancies, and research grants from BI, Cipla, GSK, Gilead Sciences, Virco, Chiron, Abbott, Indevus, and Sanofi-Pasteur and reports no stock or stock option holdings; C.J.C. has received honoraria, consultancies, and research grants from Abbott, BI, Merck, GSK, Gilead Sciences, Pfizer, and Tibotec and reports no stock or stock option holdings; P.-M. Girard has received honoraria, consultancies, and research grants from Abbott, BI, BMS, Gilead Sciences, Merck, and Tibotec and reports no stock or stock option holdings; M.L. has received honoraria, consultancies, and research grants from GSK, Janssen-Cilag, Johnson and Johnson Research, and Roche and reports no stock or stock option holdings; M.H.L. has received honoraria, consultancies, and research grants from Abbott, Tibotec, BI, Gilead Sciences, Chiron, Roche, and Pfizer and reports no stock or stock option holdings; and A.P. has received honoraria, consultancies, and research grants from Gilead Sciences and BMS and reports no stock or stock option holdings. All other authors report no potential conflicts.
Funding Information:
Financial support: SMART was supported by grants from the National Institute of Allergy and Infectious Diseases (U01AI68641, U01AI042170, and U01AI46362). The National Centre in HIV Epidemiology and Clinical Research is funded by the Australian Federal Department of Health and Ageing and is affiliated through the Faculty of Medicine with The University of New South Wales.
