Skip to content
Evevident
Original paper
2015NEJMInfectious Disease

START

Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection

RCTHIV

On this page

Overview

Immediate ART in asymptomatic HIV with CD4 >500 reduced serious AIDS-related and non-AIDS events compared with deferred therapy.

Clinical takeaway

START established treatment for all people with HIV regardless of CD4 count, assuming readiness and access.

Key result

Immediate ART halved serious events (1.8% vs 4.1%; HR 0.43).

Practice impact

Treat HIV at diagnosis rather than waiting for CD4 decline.

Evidence

Study design

Randomized controlled trial (stopped early for efficacy).

Enrollment

4,685

Follow-up

Mean 3.0 years.

Geography

Multinational

Clinical question

Should ART be started immediately in early asymptomatic HIV infection with preserved CD4 count?

Population

  • ART-naive adults with HIV and a CD4 count above 500 cells/mm3.

Intervention

Immediate ART initiation.

Comparator

Deferred ART until CD4 count fell to 350 or an AIDS event occurred.

Primary outcome

Composite of serious AIDS-related event, serious non-AIDS event, or death.

Starting ART immediately at CD4 >500 more than halved serious clinical events compared with deferring treatment.

Hazard ratio / 0.43 / CI 95% CI 0.30-0.62 / p=<0.001

Key results

  • Primary composite event: 42 patients (1.8%) with immediate ART vs 96 (4.1%) with deferred ART; HR 0.43 (95% CI 0.30-0.62; p<0.001).
  • Both serious AIDS-related and serious non-AIDS events were reduced.
  • Benefit was consistent across regions and baseline CD4 strata, supporting treatment for all.

Harms

  • Rates of grade 4 events and unscheduled hospitalizations did not differ significantly between groups.
  • Immediate therapy entails earlier, longer drug exposure with its associated toxicities and adherence demands.

Clinical Use

When to cite

  • When recommending ART initiation soon after HIV diagnosis regardless of CD4 count.

Practice impact

  • Treat HIV at diagnosis rather than waiting for CD4 decline.

Applicability

  • Most applicable to ART-naive adults with HIV and a CD4 count above 500 cells/mm3; underpins treat-all guidelines.

Limitations

  • Requires linkage to care, adherence, and reliable medication access.
  • Regimens and their toxicity profiles have evolved since the trial.
  • Relatively short mean follow-up for a lifelong therapy decision.

Common misinterpretations

  • The benefit reflects treating the individual early, complementing (not duplicating) HPTN 052's prevention finding.
  • Immediate ART is favored regardless of CD4 count, not only when CD4 is high.

Related evidence

HPTN 052 - Similar Question

Citation

INSIGHT START Study Group, Lundgren JD, Babiker AG, et al. Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection. N Engl J Med. 2015;373(9):795-807. doi:10.1056/NEJMoa1506816

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