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INSIGHT START

"Immediate Antiretroviral Therapy in Early HIV Infection". The New England Journal of Medicine. 2015.

Clinical Question

Does immediate antiretroviral therapy provide benefits over deferred antiretroviral therapy in HIV-positive adults with a CD4+ count of more than 500 cells per cubic millimeter?

Bottom Line

Immediate antiretroviral therapy in HIV-positive adults with a CD4+ count of more than 500 cells per cubic millimeter provided net benefits over starting therapy after the CD4+ count had declined to 350 cells per cubic millimeter.

Major Points

The Strategic Timing of Antiretroviral Therapy (START) trial was designed to determine the risks and benefits of immediate versus deferred initiation of antiretroviral therapy in asymptomatic HIV-positive patients with high CD4+ counts. The trial concluded with strong evidence supporting the immediate initiation of therapy, showing benefits for both serious AIDS-related and serious non–AIDS-related events, with no increased adverse effects.

Guidelines

The results of this trial provide evidence that antiretroviral therapy should be recommended for all patients diagnosed with HIV, regardless of CD4+ count, aligning individual health benefits with public health goals to reduce HIV transmission.

Design

- Multicenter, double-blind, parallel-group, randomized, placebo-controlled trial
- N=4,685 HIV-positive adults with a CD4+ count of more than 500 cells per cubic millimeter
- Immediate antiretroviral therapy (n=2,326)
- Deferred antiretroviral therapy (n=2,359)
- Median follow-up: 3.0 years

Population

- Adults aged ≥18 years
- HIV-positive
- CD4+ count of more than 500 cells per cubic millimeter
- No history of AIDS
- Generally good health

Interventions

- Immediate initiation of antiretroviral therapy
- Deferred initiation of antiretroviral therapy until CD4+ count decreased to 350 cells per cubic millimeter, development of AIDS, or another condition dictating the use of therapy

Outcomes

- Primary outcome: Composite of any serious AIDS-related event, serious non–AIDS-related event, or death from any cause
- Secondary outcomes: Serious AIDS-related events, serious non–AIDS-related events, death from any cause, grade 4 events, and unscheduled hospitalizations

Criticisms

- Despite the long duration of the study, 3 years is a short period for patients expected to require lifelong therapy, and the impact of long-term therapy is still uncertain.
- The absolute differences in outcomes between immediate and deferred therapy groups were small, impacting decision-making for some low-risk patients.
- The study did not fully evaluate the effects of immediate therapy on individual serious non-AIDS conditions like cardiovascular disease.

Funding

- National Institute of Allergy and Infectious Diseases (NIAID) and several other institutes and international bodies.
- Antiretroviral drugs were donated by several pharmaceutical companies.