Sustiva Tablet

Kaletra Tablet

The use of either the non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz (Sustiva) or the boosted protease inhibitor lopinavir/ritonavir (Kaletra) plus 2 nucleoside/nucleotide reverse-transcriptase inhibitors (NRTIs) is recommended for initial therapy for people with HIV infection.

However, it is not definitively known which of these 2 regimens has greater efficacy. Further, an alternative NRTI-sparing regimen comprised of lopinavir/ritonavir plus efavirenz may prevent toxic effects associated with NRTIs.

In this U.S. government-sponsored, open-label study (AIDS Clinical Trials Group Study 5142), published in the May 15, 2008 issue of the New England Journal of Medicine, researchers compared 3 regimens for initial therapy in HIV positive adults and adolescents:

The researchers randomly assigned 757 patients at 55 centers with a median CD4 count of 191 cells/mm3 and a median HIV-1 RNA level of 4.8 log10 copies/mL to the 3 groups.

Results

In conclusion, the study authors wrote, "Virologic failure was less likely in the efavirenz group than in the lopinavir/ritonavir group. The virologic efficacy of the NRTI-sparing regimen was similar to that of the efavirenz regimen but was more likely to be associated with drug resistance."

In an accompanying editorial, Bernard Hirschel, MD, and Alexandra Calmy, MD, wrote that the ACTG 5142 results "are difficult to put in a nutshell." Looking at HIV suppression, they wrote, "the efavirenz group had the best results, closely followed by the NRTI-sparing group and the lopinavir/ritonavir group, although the difference between the efavirenz group and the NRTI-sparing group was not significant."

"When the regimens were ranked according to the emergence of drug resistance, the winner was the lopinavir/ritonavir group, followed by the efavirenz group and the NRTI-sparing group, and again the difference between the lopinavir/ritonavir group and the efavirenz group was not significant," they continued. "Finally, as measured by the proportion of patients who discontinued or changed their treatment, all 3 groups had similar rates of adverse events."

The editorial authors noted that many participants in the present study used the NRTIs zidovudine (AZT; Retrovir) or stavudine (d4T; Zerit), which have since fallen out of favor due to toxicity. Today, the preferred NRTI backbone combinations according to the U.S. treatment guidelines are tenofovir plus emtricitabine (the 2 drugs in the Truvada fixed-dose coformulation pill; also combined with efavirenz in the Atripla pill) and abacavir plus lamivudine (the 2 agents in the Epzicom combination pill).

"[O]n the basis of this study, it seems that efavirenz plus two NRTIs is hard to beat," they wrote." In addition, efavirenz has a lower pill burden due to combination coformulations, and in most countries, efavirenz costs less than lopinavir/ritonavir.

Drs. Hischel and Calmy concluded that, "These data should challenge the 40% of clinicians who start antiretroviral treatment with a protease inhibitor and should reassure those who, in resource-limited settings, must use combinations of NRTIs and NNRTIs because they are cheaper."

6/10/08

References

SA Riddler, R Haubrich, AG DiRienzo, and others (ACTG Study 5142 Team). Class-sparing regimens for initial treatment of HIV-1 infection. New England Journal of Medicine 358(20): 2095-2106. May 15, 2008.

B Hirschel and A Calmy. Initial Treatment for HIV Infection-- An Embarrassment of Riches (Editorial). New England Journal of Medicine 358 (20): 2170-2072. May 15, 2008.

For further information

More on efavirenz (Sustiva) from HIV and Hepatitis.com.

More on lopinavir/ritonavir (Kaletra) from HIV and Hepatitis.com

Information on the fixed-dose combination efavirenz/tenofovir/emtricitabine (Atripla) from HIV and Hepatitis.com

U.S. Government Guidelines for the Treatment of HIV in Adults and Adolescents