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The Return of All-Nuke Regimens?

In a pilot study, quadruple-NRTI regimens were as potent and tolerable as standard efavirenz-based regimens.

Although NNRTIs and PIs are central to current HIV treatment strategies, avoiding these agents is sometimes desirable, especially in the case of drug interactions with antimicrobials used to treat tuberculosis (TB). Results from ACTG 5095 clearly indicated that a triple-NRTI regimen (AZT/3TC/abacavir) was inferior to efavirenz-based therapy (ACC Jun 1 2004), but few data address quadruple-NRTI regimens.

In this open-label, industry-sponsored, pilot study, researchers compared the potency and tolerability of a quadruple-NRTI regimen (AZT/3TC/abacavir + tenofovir) and a standard regimen of AZT/3TC + efavirenz in 113 treatment-naive HIV-infected patients. Both treatments were twice-daily regimens taken without regard to food intake and totaled three pills daily, making comparisons simpler and potentially more valid. The primary endpoint was viral-load change through 48 weeks, as determined by a time-weighted difference in average viral-load change from baseline to each time point.

The quadruple-NRTI and efavirenz groups were well matched at baseline for median CD4 count (153 and 194 cells/mm³) and mean viral load (5.13 and 5.26 log copies/mL). Eighty patients (71%) completed 48 weeks of treatment. In an intent-to-treat analysis, 67% of the quadruple-NRTI group and 68% of the efavirenz group achieved viral loads <50 copies/mL. Response rates were also equivalent in the on-treatment analysis. CD4 changes over 48 weeks did not differ significantly between the groups (+165 cells/mm³ in the quadruple-NRTI group and +119 cells/mm³ in the efavirenz group). Both regimens were well tolerated.

Comment: All-nucleoside regimens appeared to have been dealt a death blow when ACTG 5095 clearly showed the superiority of efavirenz-based treatment over triple-NRTI therapy. Nonetheless, the appeal of single-class treatment without cytochrome P450 3A4 interactions to worry about remains strong, particularly in areas with a high prevalence of TB. The availability of tenofovir and its potential value when combined with thymidine-analogue nucleosides have opened the door to studies of "quad-nuke" regimens. This pilot study is encouraging in that regard. A more definitive study of quadruple-NRTI regimens is being developed by the ACTG and might restore all-nucleoside regimens as viable first-line treatment approaches.

— Charles B. Hicks, MD

Published in Journal Watch HIV/AIDS Clinical Care March 29, 2006

Citation(s):

Moyle G et al. An open-label, randomized comparative pilot study of a single-class quadruple therapy regimen versus a 2-class triple therapy regimen for individuals initiating antiretroviral therapy. Antivir Ther 2006 Jan; 11:73-8.

• Medline abstract (Free)

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