CROI: Five-Drug HIV Therapy No Better than Standard

3 comment(s)

Take Posttest

BOSTON -- In a disappointing result, intensified antiretroviral therapy for acute and early HIV had no effect, a researcher said here.

After 48 weeks of treatment, patients getting five drugs and those getting the standard three had equivalent levels of HIV RNA particles in their blood, according to Martin Markowitz, MD, of the Aaron Diamond AIDS Research Center in New York City.

There was also no difference in a range of measurements of the immune system, Markowitz reported at the Conference on Retroviruses and Opportunistic Infections.

"I was disappointed," Markowitz told a late-breaker session, "because I had hoped we could go further with antiretroviral therapy than we have."

But, he said, the results halfway through the 96-week study suggest that "upping the ante from the get-go may not work."

The finding was not surprising, according to Scott Hammer, MD, chief of infectious diseases at New York-Presbyterian/Columbia University Medical Center. In patients with chronic infection, "study after study after study has shown you do not reduce the residual viral load" if treatment is intensified, Hammer said.

"You can intervene with antiretrovirals, you can drive the (HIV) RNA down, but there's an irreducible minimum that you can't get below," he told MedPage Today.

Hammer said that HIV appears to establish a reservoir very early in the disease course that so far cannot be affected by treatment, although the exact nature of the reservoir remains controversial.

It may also be true that some HIV continues to replicate despite therapy, he said.

But the question of whether combination antiretroviral treatment is as good as it can be remains "critical," Markowitz said.

Current treatments usually attack just two aspects of HIV -- the viral protease and reverse transcriptase enzymes -- but other targets are known.

To test whether a broader attack would be more effective, Markowitz and colleagues enrolled 40 patients in the early stages of infection and randomly assigned them, in a one-to-two fashion, to get either three or five medications.

The 14 patients in the three-drug arm were treated with a fixed dose combination of tenofovir and emtricitabine (Truvada) -- both reverse transcriptase inhibitors -- as well as a boosted protease inhibitor, either atazanavir (Reyataz) or darunavir (Prezista).

The 26 volunteers in the five-drug arm got the same drugs, with the addition of the entry inhibitor maraviroc (Selzentry) and the integrase inhibitor raltegravir (Isentress), he reported.

But analysis after 48 weeks showed that, among the 34 patients who remained on the study:

  • Those getting five drugs reached undetectable levels of HIV RNA in their blood faster than those getting three, but there was no significant difference in the proportion with undetectable virus by 24 weeks.
  • Three patients, all in the five-drug arm, had virological failure at 48 weeks.
  • There were no differences in levels of proviral DNA or cell-associated HIV RNA, or their rates of decay over time.
  • Patients in both arms had a robust recovery of CD4-positive T cells of about 300 cells each, but without a significant difference between the arms.
  • There were also no differences in levels of naive and total CD4 cells or markers of immune activation.

"We measured pretty much everything that can be measured," Markowitz told reporters, "and to make the story rather simple, we did not see any substantial or significant differences."

About a quarter of the patients were in the acute phase of infection, Markowitz said, but the researchers saw no different responses between them and those in the later early phase.

The study was difficult to do, he noted, because physicians were "loathe to put patients on five drugs."

The study had support from Rockefeller University, Merck, and Pfizer.

Markowitz reported financial links with Gilead Sciences, GlaxoSmithKline, Merck, Pfizer, Tibotec, and Viiv Healthcare.

Primary source: Conference on Retroviruses and Opportunistic Infections
Source reference:
Markowitz M, et al "A randomized open-label trial of 5-drug vs 3-drug standard PI-based cART initiated during acute and early HIV-1 infection: 48-week results" CROI 2011; Abstract 148LB.