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"Timing of Antiretroviral Therapy for HIV-1 Infection and Mortality". The New England Journal of Medicine. 2009. 360:1815-1826. PubMed•Full text•PDF

1 Clinical Question
2 Bottom Line
3 Major Points
4 Guidelines
5 Design
6 Population
6.1 Inclusion Criteria
6.2 Exclusion Criteria
6.3 Baseline Characteristics
7 Interventions
8 Outcomes
8.1 Primary Outcome
8.2 Secondary Outcomes
9 Criticisms
10 Funding
11 Further Reading

Clinical Question

Does early initiation of antiretroviral therapy improve survival in asymptomatic patients with human immunodeficiency virus (HIV) infection compared to deferred therapy?

Bottom Line

Early initiation of antiretroviral therapy before the CD4+ count fell below two prespecified thresholds (351 to 500 cells per cubic millimeter or >500 cells per cubic millimeter) significantly improved survival compared with deferred therapy.

Major Points

A large observational study involving 17,517 asymptomatic HIV-infected patients assessed the timing of initiation of antiretroviral therapy and its impact on survival. Patients were grouped by CD4+ counts at therapy initiation (either 351-500 cells per cubic millimeter or >500 cells per cubic millimeter), and compared with patients who deferred treatment until CD4+ counts fell below these thresholds. In patients with CD4+ counts of 351-500, deferred therapy increased the risk of death by 69% compared with early initiation. For patients with CD4+ counts >500, deferral increased mortality risk by 94%.

Guidelines

Current HIV treatment guidelines recommend initiation of antiretroviral therapy in asymptomatic patients with CD4+ counts less than 350 cells per cubic millimeter, acknowledging the lack of randomized clinical trial data regarding this recommendation.

Design

Two parallel analyses of a multicenter, observational cohort study involving patients from the United States and Canada.

Population

Inclusion Criteria
- Asymptomatic HIV-infected patients
- CD4+ count of 351-500 cells per cubic millimeter or >500 cells per cubic millimeter
- No previous antiretroviral therapy
- No history of AIDS-defining illness

Exclusion Criteria
- Not reported

Baseline Characteristics
- Patients initiating early therapy were slightly older and more likely to be white men.

Interventions

- Patients were classified into two treatment strategies: early initiation of antiretroviral therapy or deferral until CD4+ count decreased below threshold levels.

Outcomes

Primary Outcome
- Risk of death

Secondary Outcomes
- Not reported

Criticisms

- Observational study design does not eliminate possibility of confounding.
- The decision to initiate or defer therapy could have been influenced by factors not measured in this study.

Funding

National Institutes of Health and the Agency for Healthcare Research and Quality.