NEW YORK (Reuters Health) - The risk of progression to AIDS in HIV-infected patients is significantly reduced when combined antiretroviral therapy is started at a CD4 count threshold of 500 cells/microliter rather than at 350 or lower, according to a report in the Annals of Internal Medicine for April 19.

Dr. Lauren E. Cain, with the Harvard School of Public Health in Boston, Massachusetts, and colleagues explain that European and WHO guidelines recommend starting antiretroviral therapy (ART) when an asymptomatic HIV patient’s CD4 cell count has dropped to 350 or less, while US guidelines indicate a treatment initiation threshold of 500. Information from randomized trial isn’t sufficient to decide between these two strategies, the authors say, and two large observational studies have given conflicting results.

The therefore studied pooled observational data from a collaboration that includes 12 prospective cohort studies from five European countries and the United States: The team looked at all-cause mortality and a combined end point of AIDS-defining illness or death in 20,971 therapy-naive patients, with follow-up starting the first time the CD4 count fell below 500 cells/microliter.

The hazard ratio for AIDS-defining illness or death was 1.38 when ART was started at 350 rather than 500 CD4 cells/microliter, according to the report. The corresponding HR for initiating ART at a CD4 count of 200 was 1.90.

This means that approximately 48 patients would need to initiate ART when their CD4 cell count dropped below 500 rather than 350 in order to prevent 1 new case of an AIDS-defining illness or death during the first 5 years, Dr. Cain and colleagues calculated.

On the other hand, overall mortality showed little change with CD4 thresholds. Specifically, the mortality hazard ratio was 1.01 for the 350 threshold and 1.20 for the 200 threshold, compared with initiating ART at 500.

Noting that the benefit of starting ART early obviously cannot be realized if most HIV-infected patients present with CD4 counts already below this threshold, the authors add, “Thus, early HIV testing would be beneficial.”

In an editorial, Drs. Jason V. Baker and Keith Henry, with the University of Minnesota School of Medicine in Minneapolis, point out a potential societal benefit of early ART use. Given that a lower viral load is associated with lower transmission risk, “Expanded use of combined ART could substantially curtail the future HIV epidemic,” they write.

Ann Intern Med 2011;154:509-515,563-565.