96-Week Data From Gilead's Study 934 Comparing Viread(R) and Emtriva(R) to Combivir(R) Both in Combination With Sustiva(R) Published in Journal of Acquired Immune Deficiency Syndrome



    Gilead Sciences, Inc. (Nasdaq:GILD) today announced the
    publication of 96-week data from an ongoing clinical trial, Study 934,
    in the Journal of Acquired Immune Deficiency Syndrome (JAIDS). This
    study compares a once-daily regimen of Viread(R) (tenofovir disoproxil
    fumarate), Emtriva(R) (emtricitabine) and Sustiva(R) (efavirenz) to a
    twice-daily regimen of Combivir(R) (lamivudine/zidovudine) with
    Sustiva once daily. The study article, "Tenofovir Disoproxil Fumarate,
    Emtricitabine, and Efavirenz Versus Fixed-Dose Zidovudine/Lamivudine
    and Efavirenz in Antiretroviral-Naive Patients," appears in the
    December 15 issue of JAIDS (Vol. 43; issue 5).

    "The efficacy, safety and resistance profile of
    Viread/Emtriva/Sustiva in this study underscores the importance of
    this treatment option for antiretroviral therapy-naive patients," said
    lead author Anton Pozniak, MD, of the Chelsea and Westminster
    Hospital, London. "Sustiva, Emtriva and Viread were administered as
    individual agents in this trial, but a fixed-dose combination of these
    drugs is now available, offering more convenient dosing."

    Viread and Emtriva are available as once-daily Truvada(R)
    (emtricitabine and tenofovir disoproxil fumarate), the most commonly
    prescribed backbone for HIV combination therapy. Viread, Emtriva and
    Sustiva are available in the United States as ATRIPLA(TM) (efavirenz
    600 mg/ emtricitabine 200 mg/ tenofovir disoproxil fumarate 300 mg),
    the only once-daily single tablet regimen for the treatment of HIV-1
    infection in adults. ATRIPLA was developed through a U.S. joint
    venture between Bristol-Myers Squibb and Gilead Sciences. Together
    with Merck & Co., Inc., the companies recently submitted a Marketing
    Authorisation Application (MAA) for the product to the European
    Medicines Agency (EMEA).

    Ninety-six week data from this study were originally presented at
    the XVI International AIDS Conference in Toronto, Canada in August,
    2006. Data from this analysis have not been reviewed by the U.S. Food
    & Drug Administration.

    Study 934

    Study 934 is a Phase III, open-label, non-inferiority study that
    enrolled 517 HIV-infected patients in the United States and Europe.
    The study's primary endpoint was at 48 weeks and the study is
    continuing through 144 weeks. The prespecified primary efficacy
    population included 487 patients. Twenty-four patients (12 from each
    arm) who completed week 48 of the study with HIV RNA less than 400
    copies/mL did not consent to participate after week 48 and were
    excluded from the analysis. Participants were randomized to receive
    Viread 300 mg, Emtriva 200 mg and Sustiva 600 mg, all dosed once
    daily, or Combivir twice daily and Sustiva 600 mg once daily. At study
    entry, patients were treatment-naive and had HIV RNA (viral load)
    greater than 10,000 copies/mL.

    After 96 weeks of treatment (n=463), 75 percent of
    Viread/Emtriva/Sustiva patients compared to 62 percent of
    Combivir/Sustiva patients achieved and maintained viral load less than
    400 copies/mL using the Time to Loss of Virologic Response algorithm
    (TLOVR) (p=0.004; 95% CI, +4% to +21%). Sixty-seven percent of
    patients in the Viread/Emtriva/Sustiva arm compared to 61 percent of
    patients in the Combivir/Sustiva arm achieved and maintained viral
    load less than 50 copies/mL using TLOVR (p=0.16; 95% CI, -2% to +15%).
    Patients receiving Viread/Emtriva/Sustiva experienced a significantly
    greater increase from baseline in CD4 cell counts at week 96 compared
    to those receiving Combivir/Sustiva (270 vs. 237 cells/mm(3);
    p=0.036).

    There was a significant difference between the two study arms in
    terms of virologic rebound at 96 weeks (defined as having a confirmed
    viral load of greater than 400 copies/mL after achieving confirmed
    viral load of less than 400 copies/mL). Five percent of patients in
    the Combivir/Sustiva group experienced rebound compared to less than 1
    percent of Viread/Emtriva/Sustiva patients (p=0.007).

    Through 96 weeks, 43 patients in the study met criteria for
    resistance testing. The K65R mutation, which can be selected by
    Viread, did not arise in any patient. There was a significant
    difference between study arms in the development of the M184V
    mutation, which was observed in 2 patients in the
    Viread/Emtriva/Sustiva group compared with 9 patients in the
    Combivir/Sustiva group (p=0.036).

    After 96 weeks of treatment, discontinuation of study medications
    due to adverse events was significantly higher among Combivir/Sustiva
    patients compared to the Viread/Emtriva/Sustiva arm (11 vs. 5 percent,
    respectively; p=0.008). The most common cause of discontinuation
    related to study drug in at least 2 percent of patients in either arm
    include anemia (6 percent in the Combivir/Sustiva group vs. 0 percent
    in the Viread/Emtriva/Sustiva group), fatigue (2 percent in the
    Combivir/Sustiva group vs. 0 percent in the Viread/Emtriva/Sustiva
    group), nausea (2 percent in the Combivir/Sustiva group vs. less than
    1 percent in the Viread/Emtriva/Sustiva group), and rash (less than 1
    percent in the Combivir/Sustiva group vs. 2 percent in the
    Viread/Emtriva/Sustiva group).

    Patients receiving Viread/Emtriva/Sustiva had a significantly
    greater median increase in weight from baseline compared to patients
    receiving Combivir/Sustiva (2.7 kg vs. 0.5 kg, respectively; p less
    than 0.001). Patients receiving Viread/Emtriva/Sustiva had
    significantly greater median limb fat at week 96 compared to patients
    receiving Combivir/Sustiva (7.7 kg, n=144 vs. 5.5 kg, n=136,
    respectively; p less than 0.001). In addition, in a subset of patients
    with 48- and 96-week data, significant differences in median limb fat
    were observed (decrease of 0.7 kg in the Combivir/Sustiva arm; n=44;
    p=0.001; increase of 0.3 kg in the Viread/Emtriva/Sustiva arm; n=49;
    p=0.01).

    Renal adverse events were uncommon at 96 weeks, which is
    consistent with study data at 48 weeks and results from other
    randomized clinical trials involving Viread in treatment-naive and
    treatment-experienced patients. Renal safety was similar and renal
    function remained stable in the two arms of the study. No patient
    discontinued study medication due to renal events.

    Important Product Safety Information

    Lactic acidosis and severe hepatomegaly with steatosis, including
    fatal cases, have been reported with the use of nucleoside analogues
    alone or in combination with other antiretrovirals.

    ATRIPLA, Viread and Emtriva are not indicated for the treatment of
    chronic hepatitis B virus (HBV) infection and the safety and efficacy
    of these drugs have not been established in patients co-infected with
    HBV and HIV. Severe acute exacerbations of hepatitis B have been
    reported in patients who have discontinued Viread or Emtriva
    (components of ATRIPLA). Hepatic function should be monitored closely
    with both clinical and laboratory follow-up for at least several
    months in patients who discontinue ATRIPLA, Viread or Emtriva and are
    co-infected with HIV and HBV. If appropriate, initiation of
    anti-hepatitis B therapy may be warranted.

    It is important for patients to be aware that anti-HIV medicines
    including ATRIPLA, Viread and Emtriva do not cure HIV infection or
    AIDS, nor have they been shown to reduce the risk of transmission of
    HIV to others.

    Additional Important Information About ATRIPLA

    ATRIPLA is indicated for use alone as a complete regimen or in
    combination with other antiretroviral agents for the treatment of
    HIV-1 infection in adults.

    ATRIPLA is contraindicated for use with astemizole, cisapride,
    midazolam, triazolam, ergot derivatives, or voriconazole. Concomitant
    use of ATRIPLA and St. John's wort (Hypericum perforatum) or St.
    John's wort-containing products is not recommended. Since ATRIPLA
    contains efavirenz, emtricitabine and tenofovir disoproxil fumarate,
    it should not be coadministered with Sustiva, Emtriva, Viread, or
    Truvada (emtricitabine/tenofovir disoproxil fumarate). Due to
    similarities between emtricitabine and lamivudine, ATRIPLA should not
    be coadministered with drugs containing lamivudine, including Combivir
    (lamivudine/zidovudine), Epivir(R) (lamivudine), Epivir-HBV(R),
    Epzicom(TM)(abacavir/lamivudine), or Trizivir(R)
    (abacavir/lamivudine/zidovudine).

    Serious psychiatric adverse experiences, including severe
    depression (2.4%), suicidal ideation (0.7%), nonfatal suicide attempts
    (0.5%), aggressive behavior (0.4%), paranoid reactions (0.4%) and
    manic reactions (0.2%) have been reported in patients treated with
    efavirenz. In addition to efavirenz, factors identified in a clinical
    study that were associated with an increase in psychiatric symptoms
    included a history of injection drug use, psychiatric history and use
    of psychiatric medication. There have been occasional reports of
    suicide, delusions and psychosis-like behavior, but it could not be
    determined if efavirenz was the cause. Patients with serious
    psychiatric adverse experiences should be evaluated immediately to
    determine whether the risks of continued therapy outweigh the
    benefits. Fifty-three percent of patients reported central nervous
    system symptoms including dizziness (28.1%), insomnia (16.3%),
    impaired concentration (8.3%), somnolence (7.0%), abnormal dreams
    (6.2%) and hallucinations (1.2%) when taking efavirenz compared to 25%
    of patients receiving control regimens. These symptoms usually begin
    during the first or second day of therapy and generally resolve after
    the first two to four weeks of therapy. After four weeks of therapy,
    the prevalence of central nervous system symptoms of at least moderate
    severity ranged from 5% to 9% in patients treated with regimens
    containing efavirenz. Nervous system symptoms are not predictive of
    the less frequent psychiatric symptoms.

    ATRIPLA should not be given to patients with creatinine clearance
    below 50 mL/min. Renal impairment, including cases of acute renal
    failure and Fanconi syndrome (renal tubular injury with severe
    hypophosphatemia), has been reported in association with the use of
    tenofovir disoproxil fumarate, most often in patients with underlying
    systemic or renal disease, or in patients taking concomitant
    nephrotoxic agents. Some cases have occurred in patients with no
    identified risk factors. ATRIPLA should be avoided with concurrent or
    recent use of a nephrotoxic agent.

    ATRIPLA may cause fetal harm when administered during the first
    trimester to a pregnant woman. Women should not become pregnant or
    breastfeed while taking ATRIPLA. Barrier contraception must always be
    used in combination with other methods of contraception such as oral
    or other hormonal contraceptives. If the patient becomes pregnant
    while taking ATRIPLA, she should be apprised of the potential harm to
    the fetus.

    Mild to moderate rash is a common side effect of efavirenz. In
    controlled clinical trials, 26% of patients treated with efavirenz
    experienced new-onset skin rash compared with 17% of patients treated
    in control groups. Skin discoloration, associated with emtricitabine,
    may also occur. ATRIPLA should be discontinued in patients developing
    severe rash associated with blistering, desquamation, mucosal
    involvement, or fever. Liver enzymes should be monitored in patients
    with known or suspected hepatitis B or C and when ATRIPLA is
    administered with ritonavir or other medications associated with liver
    toxicity. Decreases in bone mineral density (BMD) have been seen with
    tenofovir disoproxil fumarate. Use ATRIPLA with caution in patients
    with a history of seizures. Convulsions have been observed in patients
    receiving efavirenz, generally in the presence of a known medical
    history of seizures. Redistribution and/or accumulation of body fat
    have been observed in patients receiving antiretroviral therapy.
    Immune reconstitution syndrome has been reported in patients treated
    with combination antiretroviral therapy, including the components of
    ATRIPLA.

    Saquinavir should not be used as the only protease inhibitor in
    combination with ATRIPLA. Coadministration of ATRIPLA and atazanavir
    is not recommended due to concerns regarding decreased atazanavir
    concentrations. Patients on lopinavir/ritonavir plus ATRIPLA should be
    monitored for tenofovir-associated adverse events. ATRIPLA should be
    discontinued in patients who develop tenofovir-associated adverse
    events. Coadministration of ATRIPLA and didanosine should be
    undertaken with caution. Patients receiving this combination should be
    monitored closely for didanosine-associated adverse events. See full
    prescribing information for complete list of drug-drug interactions.

    In Study 934, adverse events observed in greater than or equal to
    5% of patients in the Viread/Emtriva/Sustiva group include dizziness,
    nausea, diarrhea, fatigue, headache, and rash.

    The dose of ATRIPLA is one tablet once daily taken orally on an
    empty stomach. Dosing at bedtime may improve the tolerability of
    nervous system symptoms.

    About Viread

    In the United States, Viread is indicated in combination with
    other antiretroviral agents for the treatment of HIV-1 infection.
    Viread should not be used in combination with Truvada. Truvada should
    not be used in combination with its component drugs, Viread or
    Emtriva.

    Drug interactions have been observed when didanosine, atazanavir
    or lopinavir/ritonavir is co-administered with Viread and dose
    adjustments may be necessary. Data are not available to recommend a
    dose adjustment of didanosine for patients weighing less than 60 kg.
    Patients on atazanavir and lopinavir/ritonavir plus Viread should be
    monitored for Viread-associated adverse events, which may require
    discontinuation. When co-administered with Viread, it is recommended
    that atazanavir 300 mg be given with ritonavir 100 mg. Atazanavir
    without ritonavir should not be co-administered with Viread.

    Renal impairment, including cases of acute renal failure and
    Fanconi syndrome (renal tubular injury with severe hypophosphatemia),
    has been reported among patients taking Viread. Renal impairment
    occurred most often in patients with underlying systemic or renal
    disease or in patients taking concomitant nephrotoxic agents, though
    some cases have appeared in patients without identified risk factors.
    Decreases in bone mineral density (BMD) at the lumbar spine and hip
    have been seen with the use of Viread. The effects of
    Viread-associated changes in BMD and biochemical markers on long-term
    bone health and future fracture risk are unknown. Redistribution
    and/or accumulation of body fat have been observed in patients
    receiving antiretroviral therapy. Immune reconstitution syndrome has
    been reported in patients treated with combination antiretroviral
    therapy including Viread.

    The most common adverse events among patients receiving Viread
    with other antiretroviral agents in clinical trials were mild to
    moderate gastrointestinal events and dizziness. Moderate to severe
    adverse events occurring in more than 5 percent of patients receiving
    Viread included rash (rash, pruritis, maculopapular rash, urticaria,
    vesiculobullous rash and pustular rash), headache, pain, diarrhea,
    depression, back pain, fever, nausea, abdominal pain, asthenia and
    anxiety (Study 903). Less than 1 percent of patients discontinued
    participation because of gastrointestinal events (Study 907).

    The parent compound of Viread was discovered through a
    collaborative research effort between Dr. Antonin Holy, Institute for
    Organic Chemistry and Biochemistry, Academy of Sciences of the Czech
    Republic (IOCB) in Prague and Dr. Erik DeClercq, Rega Institute for
    Medical Research, Katholic University in Leuven, Belgium.

    About Emtriva

    In the United States, Emtriva is indicated in combination with
    other antiretroviral agents for the treatment of HIV-1 infection in
    patients over three months of age. This indication is based on
    analyses of plasma HIV-1 RNA levels and CD4 cell counts from
    controlled studies of 48 weeks duration in antiretroviral-naive
    patients and antiretroviral-treatment-experienced patients who were
    virologically suppressed on an HIV treatment regimen. In
    antiretroviral-treatment-experienced patients, the use of Emtriva may
    be considered for adults with HIV strains that are expected to be
    susceptible to Emtriva as assessed by genotypic or phenotypic testing.

    Adverse events that occurred in more than 5 percent of patients
    receiving Emtriva with other antiretroviral agents in clinical trials
    include abdominal pain, asthenia (weakness), headache, diarrhea,
    nausea, vomiting, dizziness and rash (rash, pruritis, maculopapular
    rash, urticaria, vesiculobullous rash, pustular rash and allergic
    reaction). Approximately 1 percent of patients discontinued
    participation because of these events. All adverse events were
    reported with similar frequency in Emtriva and control treatment
    groups with the exception of skin discoloration, which was reported
    with higher frequency in the Emtriva-treated group. Skin
    discoloration, manifested by hyperpigmentation on the palms and/or
    soles, was generally mild and asymptomatic. The mechanism and clinical
    significance are unknown.

    Redistribution and/or accumulation of body fat have been observed
    in patients receiving antiretroviral therapy. Immune reconstitution
    syndrome has been reported in patients treated with combination
    antiretroviral therapy including Emtriva. For pediatric patients over
    three months of age, the adverse event profile observed during
    clinical trials was similar to that of adult patients, with the
    exception of anemia and a higher frequency of hyperpigmentation.

    About Gilead Sciences

    Gilead Sciences is a biopharmaceutical company that discovers,
    develops and commercializes innovative therapeutics in areas of unmet
    medical need. The company's mission is to advance the care of patients
    suffering from life-threatening diseases worldwide. Headquartered in
    Foster City, California, Gilead has operations in North America,
    Europe and Australia. Visit Gilead on the World Wide Web at
    www.gilead.com.

    This press release includes forward-looking statements, within the
    meaning of the Private Securities Litigation Reform Act of 1995, that
    are subject to risks, uncertainties and other factors, including the
    risk that physicians may not see advantages of ATRIPLA, Viread and
    Emtriva over other antiretrovirals and may therefore be reluctant to
    prescribe these products. These risks, uncertainties and other factors
    could cause actual results to differ materially from those referred to
    in the forward-looking statements. The reader is cautioned not to rely
    on these forward-looking statements. These and other risks are
    described in detail in the Gilead Annual Report on Form 10-K for the
    year ended December 31, 2005, filed with the U.S. Securities and
    Exchange Commission. All forward-looking statements are based on
    information currently available to Gilead and Gilead assumes no
    obligation to update any such forward-looking statements.

    Full prescribing information for ATRIPLA is available at
    www.atripla.com. Full prescribing information for Viread, Emtriva and
    Truvada is available at www.gileadHIV.com.

    ATRIPLA is a trademark of Bristol-Myers Squibb & Gilead Sciences,
    LLC. Viread, Emtriva and Truvada are registered trademarks of Gilead
    Sciences, Inc.