Effective Treatment Alternative to Protease Inhibitor-Based Therapy

Data presented this week at the XIV International AIDS Conference show that a greater proportion of patients on highly active antiretroviral therapy (HAART) containing SUSTIVA(r)(efavirenz), Bristol-Myers Squibb's (NYSE:BMY) once-daily non-nucleoside reverse transcriptase inhibitor (NNRTI), achieved a viral load less than 400 copies/mL and CD4 cell counts above 200 cells/mm3 compared to a protease inhibitor (PI)-based regimen in highly immunosuppressed patients naive to therapy. The results from this study support the use of SUSTIVA in protease inhibitor sparing regimens for patients with low CD4 counts, high viral loads and opportunistic infections.

The analysis of 310 antiretroviral naive patients (92 in the arm containing SUSTIVA and two nucleoside reverse transcriptase inhibitors (NRTIs) and 218 in the arm containing a PI and two NRTIs) demonstrated that the use of a combination regimen containing SUSTIVA versus a PI-based regimen was associated with a higher proportion of patients achieving a viral load HIV-1 RNA less than 400 copies/mL after 24 months of treatment, 69.4 percent vs. 45.1 percent (ITT: missing or switch not due to simplification = failure) (p-value less than 0.05). At baseline, median HIV-RNA viral load was 351,000 copies/mL in the arm containing SUSTIVA(r) (efavirenz) and 254,000 copies/mL in the PI-containing arm.

Using the ITT: non-completer=failure (change of treatment ignored) analysis, through 24 months, 75 percent of patients on a combination regimen containing SUSTIVA achieved a viral load less than 400 copies/mL compared to 55.5 percent on a regimen containing a PI (p-value less than 0.05).

"These findings are particularly important because they should give physicians the confidence to prescribe, as well as patients to take, a PI-sparing regimen when presented with low CD4 counts, high viral loads and opportunistic infections," said Federico Pulido, M.D., HIV Unit, Hospital Universitario 12 de Octubre, Madrid, Spain. "This data helps to support the use of SUSTIVA in combination therapy for even our most immunosuppressed patients."

In addition, the data also showed that there was a statistically significant difference in the proportion of patients reaching CD4 counts higher than 200 cells/mm3 after 18 and 24 months of combination therapy with SUSTIVA (73.3 percent and 88 percent) compared to combination therapy with PIs (55.2 percent and 63 percent), respectively (p-value less than 0.05). There was no difference after 12 months (47.1 percent and 47.9 percent, respectively).

Of the 310 patients in the study, there were 27 discontinuations in the arm containing SUSTIVA and 116 in the arm containing a PI (four and 28 discontinuations, respectively, were due to virologic failure). Nine deaths were reported, four in the SUSTIVA sub-group, and five in the PI-sub-group.

Jose Arribas, M.D., at the Hospital Universitario 12 de Octubre in Madrid, Spain, performed a sub-study of the 92 antiretroviral-naive patients in this comparative study who were taking a regimen containing SUSTIVA(r) (efavirenz). The results showed that 62 percent of the patients had baseline CD4 counts below 50 cells/mm3 and 84 percent had baseline HIV-1 RNA above 100,000 copies/mL. Mean increases in CD4 counts over baseline values were 80, 115 and 173 cells/ mm3 at weeks 12, 24 and 48, respectively. Virologic response (HIV-1 RNA less than 50 copies/mL) at weeks 24 and 48 respectively was measured at 63 percent and 69 percent using virologic response treated analysis (ITT analysis for treated subjects).

SUSTIVA is a once-daily non-nucleoside reverse transcriptase inhibitor (NNRTI) used in combination therapy for the treatment of HIV. In February, the FDA approved a new formulation of SUSTIVA -- a 600 mg tablet once-daily, an option to three 200 mg capsules once-daily (as SUSTIVA has been used since it was approved in September 1998).

In February 2002, the U.S. Department of Health and Human Services (DHHS) continued, for the third year in a row, to list SUSTIVA as the only non-nucleoside reverse transcriptase inhibitor "strongly recommended" for use in first-line combination with NRTIs for the treatment of HIV-infected individuals. It is recommended that SUSTIVA be taken on an empty stomach, preferably at bedtime.

Many patients have dizziness, trouble sleeping, drowsiness, trouble concentrating, and/or unusual dreams when taking SUSTIVA. These feelings tend to go away after taking SUSTIVA for a few weeks. A small number of patients taking SUSTIVA have reported severe depression, strange thoughts, or angry behavior. There have been occasional reports of suicide but SUSTIVA has not been established as the cause. One of the most common side effects is rash which is usually mild and goes away in a few weeks.

SUSTIVA(r) (efavirenz) should not be taken with Hismanal(r) (astemizole), Propulsid(r) (cisapride), Versed(r) (midazolam), Halcion(r) (triazolam) or ergot derivatives. Tell your doctor about any medication or herbal products (particularly St. John's wort) that you are taking. Women should not become pregnant or breastfeed while taking SUSTIVA. SUSTIVA does not cure HIV or prevent passing HIV to others.

Bristol-Myers Squibb Company is a $19 billion pharmaceutical and related health care products company whose mission is to extend and enhance human life.

For full SUSTIVA prescribing information, please visit the company's website at http://www.BMSVirology.com or call 1-800-426-7644.

SUSTIVA(r) is a registered trademark of Bristol-Myers Squibb Pharma Company.

The other brands listed are the registered trademarks of their respective owners and are not the trademarks of Bristol-Myers Squibb Company.