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Open Access Debate

When to start antiretroviral therapy: as soon as possible

Ricardo A Franco1 and Michael S Saag2*

Author Affiliations

1 Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, 1900 University Boulevard, THT 229, Birmingham, AL, 35294, USA

2 Jim Straley Chair in AIDS Research, Center for AIDS Research, University of Alabama at Birmingham, 845 19th Street South, BBRB 256, Birmingham, AL 35294-2170, USA

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BMC Medicine 2013, 11:147  doi:10.1186/1741-7015-11-147

Published: 14 June 2013

Abstract

Background

The debate regarding ‘When to Start’ antiretroviral therapy has raged since the introduction of zidovudine in 1987. Based on the entry criteria for the original Burroughs Wellcome 002 study, the field has been anchored to CD4 cell counts as the prime metric to indicate treatment initiation for asymptomatic individuals infected with Human Immunodeficiency Virus. The pendulum has swung back and forth based mostly on the relative efficacy, toxicity and convenience of available regimens.

Discussion

In today’s world, several factors have converged that compel us to initiate therapy as soon as possible: 1) The biology of viral replication (1 to 10 billion viruses per day) strongly suggests that we should be starting early. 2) Resultant inflammation from unchecked replication is associated with earlier onset of multiple co-morbid conditions. 3) The medications available today are more efficacious and less toxic than years past. 4) Clinical trials have demonstrated benefits for all but the highest CD4 strata (>500 cells/μl). 5) Some cohort studies have demonstrated the clear benefit of antiretroviral therapy at any CD4 count and no cohort studies have demonstrated that early therapy is more detrimental than late therapy at the population level. 6) In addition to the demonstrated and inferred benefits to the individual patient, we now have evidence of a Public Health benefit from earlier intervention: treatment is prevention.

Summary

From a practical, common sense perspective we are talking about life-long therapy. Whether we start at a CD4 count of 732 cells/μl or 493 cells/μl, the patient will be on therapy for over 40 to 50 years. There does not seem to be much benefit in waiting and there likely is significant long-term harm. Do not wait. Treat early.

The counter-argument to this debate topic can be freely accessed here: http://www.biomedcentral.com/1741-7015/11/148 webcite.

Keywords:
HIV infection; CD4 lymphocyte count; When to start; Antiretroviral therapy; Early treatment