Major clinical outcomes in patients not treated with antiretroviral therapy (ART) at baseline in SMART; a rationale for a trial to examine early treatment of HIV disease
Objectives: SMART randomized 5472 HIV infected patients with CD4+ cell counts > 350/mL to intermittent ART based on CD4+ cell count <250 cells/mL or > 350 cells/mL versus continuous ART (DC and VS arms respectively). Follow-up of patients not on ART at entry informs discussions on the optimal time to commence ART.
Methods: ART naïve (n=251) or patients who had not taken ART for > 6 months (n=227) were included. Categories of clinical outcome that comprised i) opportunistic disease (OD) and all cause mortality, ii) OD (fatal and non-fatal), iii) serious non-AIDS (cardiovascular, renal and hepatic disease, non-AIDS defining cancers, and deaths from non-OD causes), and iv) the composite of ii and iii, were assessed. Events were compared between the DC and VS arms using Cox models and summarized with hazard ratios (HR) and 95% confidence intervals (CI).
Results: 229 and 249 patients were randomized to the DC and VS arms. Median CD4+ cell count and plasma HIV RNA were 447 cells/mL and 4.5 log copies/mL. Duration of ARV exposure was 17.6% and 90.0% for DC and VS patients respectively. Clinical events and HR (95%CI) are summarized below for an average 18 months follow-up. Results were similar for events in ART naïve patients.
|Events||DC (rate)||VS (rate)||HR (DC/VS)||95%CI||p-value|
|OD/death||15 (4.8)||4 (1.1)||4.36||1.44, 13.1||0.01|
|OD||11 (3.5)||3 (0.8)||4.40||1.20, 15.7||0.02|
|Serious non-AIDS||12 (3.9)||2 (0.5)||7.04||1.58, 31.5||0.01|
|Composite||21 (7.0)||5 (1.3)||5.00||1.90, 13.4||0.001|
Conclusions: These data indicate ART may reduce AIDS and non-AIDS morbidity and mortality in patients with early HIV disease. Along with observational studies, these results support the conduct of a randomized, controlled trial to determine the risks/benefits of commencing ART with CD4+ cell counts > 350/mL.
4th IAS Conference on HIV Pathogenesis, Treatment and Prevention
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Major clinical outcomes in patients not treated with antiretroviral therapy (ART) at baseline in SMART; a rationale for a trial to examine early treatment of HIV disease.
4th IAS Conference on HIV Pathogenesis, Treatment and Prevention: