NRTI Regimen Improves Lipid Profile

An AIDS regimen with a single-class triple nucleoside reverse transcriptase inhibitor (NRTI), given after successful induction with standard antiretroviral therapy (ART), has similar antiviral efficacy compared to continuation of a proteasome inhibitor-based regimen, and with improved serum lipids, according to a new study.

“Although NRTI-only regimens are no longer preferred regimens, this study shows that we can safely fall back on an NRTI-only regimen in special circumstances in patients with adequately suppressed HIV replication. Compared with continuing standard combination ART, such a switch also offers metabolic advantages,” state the researchers led by Dr HG Sprenger of the University of Groningen, Department of Internal Medicine, in Groningen, The Netherlands.

The researchers hypothesized that a triple NRTI regimen could be used safely as a maintenance regimen after successful virological suppression with standard combination ART. The study was initiated at a time when preferred regimens were still complex with a high pill burden and with more concerns about toxicity resulting in, for example, lipodystrophy, they note.

The randomized, prospective, 96-week study included ART-naive patients using protease inhibitor-based triple combination ART as induction therapy, followed by maintenance with abacavir/lamivudine/zidovudine (ABC/3TC/ZDV) in those who reached an undetectable plasma HIV-1 RNA level of less than 50 HIV-1 RNA copies/mL.

The study enrolled 207 patients, predominantly Caucasian (79%), in the induction phase; slightly more than one-third of them did not reach the maintenance phase, primarily because they did not achieve virological suppression before week 18 or because of side effects.

At 96 weeks, two-thirds of the 59 patients continuing the proteasome inhibitor regimen and nearly three-quarters of the 61 patients receiving ABC/3TC/ZDV had HIV-1 RNA < 400 copies/mL, which was the primary endpoint. “This established ABC/3TC/ZDV as non-inferior to continued proteasome inhibitor treatment,” the researchers state. Just under two-thirds of patients in both arms had HIV-1 RNA < 50 copies/mL, again showing non-inferiority.

Patients with higher initial viral loads (HIV-1 RNA > 100 000 copies/mL) tended to have less beneficial responses, they note.

“This is the first prospective trial looking at ABC/3TC/ZDV maintenance after a 3-drug 2-class induction regimen and the only trial comparing the triple-NRTI regimen with a boosted proteasome inhibitor regimen,” the researchers state.

The results are consistent with the conclusions of a recently published Cochrane review of the use of abacavir-based triple-NRTI regimens for maintenance therapy after successful induction therapy with a proteasome inhibitor-based regimen, which showed an overall failure rate comparable to that of continuing a proteasome inhibitor regimen or to switching to a non-nucleoside reverse-transcriptase inhibitor.

“In special circumstances, triple-NRTI regimens are potentially advantageous because they have a low pill burden, are well tolerated, have fewer drug interactions, have no dietary restrictions, are available in alternative formulations, have a class-sparing effect, and have low costs,” the researchers state. “Furthermore, in our study we showed improvement in lipid profiles, especially with regard to total cholesterol and triglycerides. Because of the increased incidence of cardiovascular disease found for cumulative exposure to proteasome inhibitors, these effects on dyslipidemia are an additional advantage.”

The researchers published their results in the February 2015 HIV Medicine.