Long-term HIV study confirms lack of advantage of three-class strategy for initial antiretroviral therapy

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The Pharmaceutical Journal
Vol 277 No 7432 p762
23/30 December 2006

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Long-term HIV study confirms lack of advantage of three-class strategy for initial antiretroviral therapy

HIV

HIV: even consistent differences in viral suppression did not translate to differences in clinical outcomes

For HIV-infected patients, a treatment regimen containing three classes of antiretroviral drugs offers no advantages over a two-class strategy for immunological and clinical outcomes, and is associated with increased toxic effects, data from a long-term trial reveal (Lancet 2006;368:2125).

The trial, known as the FIRST (flexible initial retrovirus suppressive therapies) study, involved 1,397 treatment-naive patients and set out to answer two questions: Is it better to begin initial antiretroviral therapy with a three-class strategy than with a two-class strategy? And, which of the two-class strategies (protease inhibitor-based or non-nucleoside reverse transcriptase inhibitor-based) is better as initial therapy?

Treatment strategies used in the FIRST study

• PI strategy (PI, mainly nelfinavir, plus two nucleoside reverse transcriptase inhibitors [NRTIs], mainly zidovudine and lamivudine)

• NNRTI strategy (NNRTI, mainly efavirenz plus two NRTIs)

• Three-class strategy (PI plus NNRTI plus one or two NRTIs)

Researchers randomly allocated patients to one of three starting treatment strategies (see Panel right) and followed them for an average of 60 months. They found that the three-class strategy did not result in a greater increase in CD4 cell count than the two-class strategies, and had the disadvantage of increased toxic effects.

In a comparison of the two two-class strategies, the researchers found that patients assigned to the non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen had better virological outcomes than patients allocated to the protease inhibitor (PI) strategy. However, the researchers point out that even consistent differences over time in viral suppression did not result in differences in the study’s composite endpoint of an AIDS-defining event or death, or in mean change in CD4 cell count.

The researchers write: “It seems reasonable to conclude that starting treatment with either an NNRTI-based regimen or a PI-based regimen, but not both together, are good strategies for long-term antiretroviral management in treatment-naive patients with HIV with a wide range of baseline CD4 cell counts and diverse demographics.”