The Pharmaceutical Journal
Vol 280 No 7502 p589
17 May 2008

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Efavirenz more effective than lopinavir/ritonavir

A regimen of efavirenz plus two nucleoside reverse-transcriptase inhibitors (NRTIs) is more effective than lopinavir/ritonavir plus two NRTIs for initial therapy of HIV-1 infection, new data show (New England Journal of Medicine 2008;358:2095).

In an open-label study, US researchers set out to compare three regimens: they randomly assigned 757 HIV-1 infected patients, aged at least 13 years, and who had not received previous antiretroviral therapy, to receive efavirenz plus two NRTIs (efavirenz group), lopinavir/ ritonavir plus two NRTIs (lopinavir/ritonavir group) or lopinavir/ritonavir plus efavirenz (NRTI-sparing group).

At a median follow-up of 112 weeks, the time to virologic failure was found to be longer in the efavirenz group than in the lopinavir/ritonavir group (P=0.006).

However, those patients receiving either of the lopinavir/ritonavir regimens had greater increases in CD4 cell count than those in the efavirenz group at week 96 (but not at week 48).

The researchers say that the regimen of efavirenz plus two NRTIs had a greater overall virologic efficacy even when the analysis was restricted to patients with a high level of adherence. They add that this regimen seemed to suppress HIV-1 levels more rapidly than regimens containing lopinavir/ritonavir — although the clinical significance of the difference is unknown.

In addition, the NRTI-sparing group was found to have a virologic efficacy similar to that of efavirenz group, but resistance to non-nucleoside reverse-transcriptase inhibitors and lipid abnormalities, especially elevated triglycerides, were more frequent, the researchers say.

They suggest that these effects “should dampen enthusiasm for routine use of this [lopinavir/ritonavir plus efavirenz] regimen”. However, the data support the use of such treatment in specific clinical situations in which options are limited, they add.

The number of regimen-failure outcomes owing to adverse events was similar among all three study groups and there was no significant difference in the time to treatment-limiting toxicity, the researchers report.

They comment: “These results highlight the complexity of choosing initial therapy. Selection of initial therapy for an individual patient should take into consideration many factors, including virologic and immunologic response, tolerability, short-term and long-term toxicity and the resistance consequence associated with virologic failure.”

The authors of an accompanying editorial (ibid, p2170), from Geneva University Hospital, Switzerland, add: “On the basis of this study, it seems that efavirenz plus two NRTIs is hard to beat.”