NEJM paper: NA-ACCORD cohort study on when to start treatment

Nathan Geffen, TAC

In the last issue of HTB we reported Mira Kitahata’s presentation at CROI of an analysis of the NA-ACCORD database to determine when to start treatment. The study has since been published in the NEJM and sheds considerable light on questions that arose from the CROI presentation. [1]

Kitahata’s team conducted two analyses. The first analysed over 8,000 patients with CD4 counts of 350 to 500. Just over 2,000 began treatment immediately and about 6,200 deferred. The relative risk of death in the deferred group was 1.69 (1.26-2.26; p<0.001).

In the second analysis, about 2,200 of 9,100 patients with CD4 counts above 500 initiated treatment and 6,935 deferred. The relative risk of death in the deferred group was 1.94 (1.37-2.79; p<0.001).

The crude death rate in the early-therapy 351-500 CD4 group was 1.6 per 100py. It was 1.3 per 100py in the early therapy group in patients with CD4 counts above 500.

In an accompanying editorial, Paul Sax and Lindsey Baden state that the “study adds to a growing body of data supporting earlier treatment for HIV infection.” They also explain, “Potential additional benefits of earlier therapy for HIV may include a lower rate of drug-specific toxic effects, a greater likelihood of achieving a normal CD4+ count, a reduction in immune activation and inflammation, and a decreased risk of HIV transmission.”[2]

They continue, “Analyses of cost-effectiveness have shown that antiretroviral therapy also compares favourably with other widely adopted medical interventions. Increasing the CD4+ threshold to start therapy at a range of 350 to 500 cells/mm3 would add only a few years of additional therapy onto projected decades of treatment and hence generate a relatively small added lifetime cost.” While this argument is true for wealthy countries, it is not clear that it is applicable to poorer ones.

However Sax and Baden conclude with the following important caution, “The NA-ACCORD data do not provide definitive proof that we should be starting antiretroviral therapy in all patients with HIV infection. Such a conclusion would require data from a randomised, prospective clinical trial, and at least three such studies are either ongoing or planned. However, the supportive evidence for the benefits of earlier therapy continues to increase, making strategies to identify patients with HIV infection before the onset of substantial immunodeficiency all the more compelling.”

The START trial, which has begun, serves this purpose.


1. Kitahata M. et al. Effect of Early versus Deferred Antiretroviral Therapy for HIV on Survival. NEJM. 2009 Apr 30;360(18)

2. Sax P. et al. When to Start Antiretroviral Therapy — Ready When You Are? NEJM. 2009 Apr 30;360(18).

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