Special Coverage: Retroviruses Conference 2006
Study says triple NRTI regimens are not as effective as those also containing NNRTI
Men and women fared the same under treatment
A recent study that compares non-protease inhibitor regimens found that patients taking a triple nucleoside reverse transcriptase inhibitor (NRTI) regimen do not achieve as effective viral suppression as those taking a regimen containing two NRTIs and one non-nucleoside reverse transcriptase inhibitor (NNRTI).1
"As the main study found, a triple nucleoside regimen does not achieve as good a response and less people are as likely to get good suppression of viral load as people who start antiretroviral therapy with a NNRTI-containing regimen," says Kathleen Squires, MD, professor of medicine and director of the Division of Infectious Diseases, at Jefferson Medical College, Thomas Jefferson University in Philadelphia, PA.
The phase III, double-blind, placebo-controlled study randomized patients to take zidovudine (ZDV)/lamivudine (3TC)/abacavir (ABC), or ZDV, 3TC, and efavirenz (EFV), or ZDV, 3TC, ABC plus efavirenz.1
"Our first major objective was to see whether the drop in viral load would be the same across the three arms of the study," Squires says. "The other objective was to look at how rapidly viral load falls, measure the frequency determination in the regimens, and show the dynamics of HIV infection."
Investigators also were interested in whether viral suppression would differ between men and women since most studies are done primarily with men and some data has suggested that viral loads in men and women are somewhat different, Squires notes.
"The second objective was to look at whether there were differences in viral loads of men and women when they started the study and then see how fast viral load fell in men and women once they started therapy," Squires adds.
Most of the participants of the main study were willing to have their blood drawn on nearly a daily basis, and they agreed to participate in the sub-study, she says.
Analysis of the three treatment arms showed that viral decay was faster in one of the two efavirenz arms. The arm that contained efavirenz plus two NRTIs resulted in more rapid viral decay than the triple-NRTI arm and the triple NRTI plus NNRTI arm, Squires says.
"There was a trend with the triple-nucleoside arm, but there was no statistical difference," she adds. "The parent study was stopped because the triple-nucleoside arm was not performing as well as the efavirenz plus two NRTI arm."
The gender analysis found that the patients all had fairly advanced HIV infection, and there was no difference at baseline in the viral loads of men and women, Squires says.
"When we measured viral dynamics there was no difference in the rate at which viral load fell in men and women after starting therapy," Squires says. "That tells us the drug regimens are equally effective in men and women."
This information is important because existing data from clinical trials come primarily from men, she notes.
"We know for a lot of disease conditions men and women are different in terms of responses to therapy and symptoms and so forth," Squires explains. "So it's important to look at both men and women and say these drugs do the same thing or different things, and in this study we can say the drug's ability to lower viral load appears to be equally effective in both men and women."
The patients included in this research had fairly advanced HIV disease with a median CD4 cell count at the time they started therapy of 250, Squires says.
"At the time this clinical trial started, it was at a time when we weren't treating HIV patients until they were more advanced in their infection," Squires says.
"The retroviruses conference may change that because of some of the presentations," Squires adds. "There is accumulating evidence that perhaps it's not as good to wait until patients are more advanced in HIV disease, especially since the regimens we're using today are much easier for patients to take in terms of number of pills, times of day, and in terms of side effects, which tend to be much milder than what we saw previously."
The latest research, including studies presented at the 13th Conference on Retroviruses and Opportunistic Infections, held Feb. 5-8, 2006, in Denver, CO, suggests that maybe HIV clinicians are waiting too long to treat patients, Squires says.
- Squires KE, et al. ACTG A5166s: viral decay rates in men and women receiving triple-nucleoside (NRTI)-or Efavirenz (EFV)-containing antiretroviral therapy: Viral Dynamics Substudy of ACTG A5095. Presented at the 13th Conference on Retroviruses and Opportunistic Infections, held Feb. 5-8, 2006, in Denver, CO. Abstract: 110.