Temporary anti-retroviral therapy during the first stage of HIV infection can delay the time to long-term treatment, researchers reported.

In a randomized trial, early treatment reduced the so-called viral set point and also delayed the need to re-start therapy after a planned interruption, according to Marlous Grijsen, MD, of the University of Amsterdam, and colleagues.

The findings suggest that 24 weeks of treatment started during primary HIV infection has a “clear clinical benefit,” Grijsen and colleagues reported online in PLoS Medicine.

The issue of how to manage HIV patients during primary infection has been controversial and the evidence of benefit for early treatment conflicting, the researchers noted.

However, this study - the Primo-SHM trial, conducted in 13 centers on the Netherlands - adds to the evidence that early treatment is beneficial, they said. Indeed, other investigators, looking at the same issue, reported a similar finding in 2011.

In the Dutch study, patients were recruited between May 1, 2003 and March, 31, 2010 and randomly assigned to no immediate treatment, or combined anti-retroviral therapy for 24 or 60 weeks.

Patients in the treatment arms would stop after the defined period and re-start therapy when clinically indicated. Patients in the no-treatment arm remained off therapy until clinically indicated.

The study was designed to evaluate the effect of the various approaches on the viral set point, defined as the viral load 36 weeks after randomization in the no-treatment arm and 36 weeks after treatment interruption in the other arms.

It was also intended to look at the total time that patients were off therapy before full-time continuous treatment was started.

Those who needed therapy when they enrolled, based on either clinical symptoms or the count of CD4-positive T cells, were randomly assigned to one of the treatment arms, but were not included in analysis of the primary endpoints. Instead, they were part of a secondary analysis aimed at seeing whether 24 or 60 weeks of therapy was the better option.

All told, the researchers had data from 168 patients, including 115 who were part of the main analysis and 53 who were part of the secondary analysis.

They found that of the 115 patients randomized over the three study arms, the average viral set point was 4.8 log10 copies of HIV RNA per milliliter of plasma, compared with 4 and 4.3 log10 copies/ml in the 24- and 60-week treatment arms. The difference between treatment and no-treatment arms was significant at P<0.001.

The median total time off therapy in the no-treatment arm was 0.7 years versus 3 years in the 24-week arm and 1.8 years in the 60-week arm.

A log rank test comparing all three arms was significant at P<0.001.

In Cox regression analyses, adjusted for various possible confounders, there was no significant difference in median time off therapy between the two treatment arms.

The implication is that 24 weeks of combined anti-retroviral therapy is enough to yield a lower viral set point and delay the time for continuous treatment, the researchers stated.

Grijsen and colleagues concluded that extended follow up is needed to evaluate the long-term benefits of such early treatment. However, they argued, "starting (antiretroviral therapy) when the patient is ready to do so seems the most reasonable advice" for patients with primary HIV infection.

The study was investigator-driven and had no external sponsor or specific source of funding. The journal said the authors had declared no competing interests.

Primary source: PLoS Medicine
Source reference: Grijsen ML, et al. “No treatment versus 24 or 60 weeks of antiretroviral treatment during primary HIV infection: The Randomized Primo-SHM Trial” PLoS Med 9: e1001196.