Efavirenz plus two NRTIs may improve virologic efficacy

Study data highlight the complexity of choosing initial therapy.

Issue: June 2008

When taken in combination with two nucleoside reverse transcriptase inhibitors, efavirenz was less likely to lead to virologic failure among patients with HIV when compared with lopinavir-ritonavir, according to researchers from the AIDS Clinical Trials Group Study A5142 Team.

“The efavirenz [Sustiva, Bristol-Myers Squibb] plus two NRTI regimen has become the ‘gold standard’ against which all future regimens should be judged. However, all three study regimens performed quite well with large increases in CD4 cell counts and with suppression of HIV viral load,” Sharon A. Riddler, MD, associate professor of medicine in the division of infectious diseases and a member of the HIV-AIDS unit at the University of Pittsburgh, told Infectious Disease News.

Three treatment regimens

The researchers conducted a phase-3, multicenter, randomized trial. They enrolled 753 patients with HIV aged 13 years and older. The researchers randomly assigned the patients to one of three regimens:

Efavirenz group: 600 mg of efavirenz once daily plus two NRTIs.
Lopinavir-ritonavir group: combination of 400 mg of lopinavir and 100 mg of ritonavir (Kaletra, Abbott) twice daily plus two NRTIs.
NRTI-sparing group: 533 mg of lopinavir and 133 mg of ritonavir twice daily plus 600 mg of efavirenz once daily.

“We randomly assigned patients with a median CD4 count of 191 cells/mL³ and a median HIV RNA level of 4.8 log₁₀ copies/mL to the three groups,” the researchers wrote.

Baseline characteristics indicated 80% of the study population was male and 64% were nonwhite. Median plasma HIV RNA level was 64,203 copies/mL. The median CD4 cell count was 191 cells/mL³.

Virologic failure

“As defined in the protocol, virologic failure occurred in 60 of 250 patients in the efavirenz group; in 94 out of 253 patients in the lopinavir-ritonavir group; and in 73 of the 250 patients in the NRTI-sparing group,” the researchers wrote.

Furthermore, when virologic failure occurred, antiretroviral resistance mutations were more frequent in the NRTI-sparing group when compared with the other two groups.

Results of the study indicated that at week 112, the efavirenz group had a longer time to virologic failure when compared with the lopinavir-ritonavir group (P=.006).

At week 96, 89% of patients in the efavirenz group, 83% of patients in the NRTI-sparing group and 77% of patients in the lopinavir-ritonavir group had fewer than 50 copies/mL of plasma HIV RNA.

“For the unusual patient who cannot take NRTI, an NRTI-sparing regimen of efavirenz plus lopinavir was effective. Although this particular NRTI-sparing regimen is not likely to become widely used, because of pill burden or side effects, there may be other NRTI-sparing or two drug regimens that will be studied in the future,” Riddler said.

Virologic failure or discontinuation of the drug regimen for toxicity occurred in 38% of patients in the efavirenz group; 50% of patients in the lopinavir-ritonavir group; and 43% of patients in the NRTI-sparing group.

Among patients who were receiving the assigned drug from baseline to week 12, 62% reported having missed no doses.

According to the researchers, these results highlight the complexity of choosing initial therapy.

“For most patients, a once-daily regimen of efavirenz plus two NRTIs will work well and since this is already the most common type of regimen used, these findings may not change treatment for the majority of patients,” Riddler said. “However, our study showed that this regimen was effective even for patients with higher viral load so it is probably not necessary to use a more complicated protease inhibitor regimen for these patients either.” – by Jennifer Southall

For more information:

Riddler SA, Haubrich R, DiRienzo G, et al. Class-sparing regimens for initial treatment of HIV-1 infection. N Engl J Med. 2008;358:2095-2106.