New Research Backs Early HIV Therapy

April 29, 2009 -- Starting HIV treatment earlier greatly improves survival, researchers report in this week's New England Journal of Medicine.

The finding is likely to spark a new debate over the benefits and drawbacks of early HIV therapy vs. deferred treatment.

Since the introduction of the first antiretroviral therapy more than 20 years ago, the optimal time to begin HIV treatment has been a matter of great controversy. Recommendations have wavered between an aggressive early therapy and a more cautious approach.

Proponents argue that antiretroviral drugs greatly benefit patients, and newer ones are safer and more effective than ever and do not need to be taken as often as in the past. Opponents say long-term use of such medicines can cause serious toxic effects on the heart, kidney, liver, and other parts of the body. It may also lead to drug resistance.

Many doctors recommend starting therapy in patients without symptoms when the level of CD4+ cells, a type of white blood cell, drops below 350 cells per cubic millimeter. CD4+ cells, also known as T-4 or T-helper cells, are produced by the body's immune system. They normally help fight infections. However, HIV damages the body's immune system; the number of CD4+ cells in the body drops as an HIV infection gets worse.

Comparing Early Treatment to Delayed Treatment

Until now, well-controlled studies comparing early treatment to deferred treatment have been lacking. For the current study, Mari M. Kitahata, MD, of the University of Washington Medical Center in Seattle, evaluated more than 17,000 HIV-positive patients who had never received treatment and grouped them according to their CD4+ counts at baseline:

• Those with a CD4+ count of 351 to 500 cells
• Those with a CD4+ count of more than 500 cells

The team further divided the groups into two subcategories and compared their risk of death:

• Early-therapy group: Treatment began before the CD4+ count dropped below 350. Patients in this group were mostly white men and slightly older than those in the other group.
• Deferred-therapy group: Patients waited to start treatment until their CD4+ counts dropped below 350._?

The combined analysis revealed that starting HIV treatment earlier significantly decreased the patient's risk for death.

In patients with an initial CD4+ count of 351-500 cells:

• A patient's risk for death increased by 69% when treatment was delayed until the count dropped below 350.

In patients who initially had a CD4+ count greater than 500:

• Deferring treatment until the count fell below 500 increased the risk of death by 94%.

The risk for death remained consistent even when excluding those with a history of injection-drug use, a habit that is associated with higher rates of death, treatment deferral, and noncompliance to therapy. Older age was an independent risk factor for death. Most deaths were due to non-AIDS-related causes, including kidney disease, heart disease, liver disease, and cancer.

In an accompanying editorial, Boston-based doctors Paul E. Sax, MD, and Lindsey R. Baden, MD, urge caution at interpreting the study results, adding that it "does not provide definitive proof that we should be starting antiretroviral therapy in all patients with HIV infection." They agree, however, that evidence supporting earlier initiation of therapy continues to increase.