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Standard Triple-Drug Regimens Remain the Best for Initial Therapy
Efavirenz-based regimens appear to be particularly effective.
As more than two dozen approved antiretrovirals jostled for a toehold in the marketplace, a handful of studies addressed the question of which combinations are "best" for treatment-naive patients.
Two boosted PIs competed in the KLEAN study: lopinavir/ritonavir and ritonavir-boosted fosamprenavir, each given with an abacavir/3TC backbone. At 48 weeks, virologic outcomes for the two regimens were indistinguishable across all pretreatment CD4 and viral-load strata, as were adverse event patterns, including lipid abnormalities (see ACC’s IAS meeting report). These results prompted the U.S. Department of Health and Human Services to add ritonavir-boosted fosamprenavir to its "preferred" list of initial treatment options.
Other studies this year examined variations on the standard theme of two NRTIs plus a PI or NNRTI. In ACTG 5095, investigators found no advantage from adding abacavir to AZT/3TC + efavirenz, even among patients with the highest pretreatment viral loads. Conversely, patients who received the three NRTIs alone, without efavirenz, had substantially worse outcomes, and that arm was eliminated early from the study (see ACC’s IAS meeting report).
The INITIO trial, similarly, showed no advantage to combining both efavirenz and nelfinavir (rather than each drug alone) with a ddI + d4T backbone. After 3 years, treatment-naive subjects who received efavirenz without nelfinavir had the highest rates of complete virologic suppression, whereas those who received it with nelfinavir had the most drug intolerance requiring a treatment change (Lancet 2006; 368:287).
ACTG 5142 removed NRTIs from the mix entirely, evaluating an initial regimen of lopinavir/r + efavirenz compared with standard regimens using each drug by itself with a dual-NRTI backbone. At 96 weeks, the group receiving the standard efavirenz-based triple-drug regimen had the highest rates of virologic suppression. Treatment-limiting toxicity rates were similar in all groups (see ACC’s IAS meeting report).
Finally, in what can only be termed a refreshing change from the usual dependence on surrogate outcomes to rank drug choices, the giant Antiretroviral Therapy Cohort Collaboration performed a meta-analysis looking at both virologic and clinical outcomes from a dozen treatment studies. Although small statistical differences could be found among many of the common drug combinations, the bottom line supported a standard triple-drug efavirenz-based regimen from both virologic and clinical standpoints (ACC Sep 1 2006).
In sum, this year’s crop of studies suggests that the standard three-drug approach to initial treatment remains the best way to use presently available agents. An increasing body of evidence now supports efavirenz-based regimens as particularly effective.
— Abigail Zuger, MD
Published in AIDS Clinical Care December 29, 2006