Elvucitabine/Efavirenz/Tenofovir vs. Lamivudine/Efavirenz/Tenofovir in HIV-1 Infected, Treatment Naive Subjects

Sixty HIV-1-infected, clinically stable, treatment-naïve adults with no acquired
immunodeficiency syndrome (AIDS)-defining events during the 3 months prior to screening will
be randomly assigned to 1 of 2 treatment groups. Subject plasma HIV-1 RNA levels must be
greater than or equal to 5000 copies/mL and CD4 cell counts must be greater than 200
cells/mL and less than 500 cells/mL at Screening. Subjects must be sensitive to
elvucitabine, lamivudine, and emtricitabine as demonstrated by the absence of the M184V,
M184I, and D237E mutations by TRUGENE HIV-1 Genotyping Kit. Subjects must be genotypically
sensitive to efavirenz (negative for K103 or Y188L mutations) and tenofovir (negative for
K65R mutation) as demonstrated by TRUGENE HIV-1 Genotyping Kit. They must have acceptable
hematologic and chemistry parameters.

Subjects whose HIV-1 RNA levels have decreased at least 2 logs or to below 400 copies/mL by
Week 10 may be considered eligible to enter the extension phase of up to 36 weeks of
additional treatment. Subjects in the extension phase will be evaluated at Weeks 14, 16, and
every 4 weeks until week 96.

Once all subjects have completed 12 weeks of treatment, and the data are available for all
visits through Week 12, the database will be locked and the treatment assignments will be
unblinded. Any subject who has had less than 48 weeks of treatment will be allowed to
continue on the same treatment as initially assigned on an open-label basis through 48
weeks. All subjects will have 2 post treatment follow-up visits, at 1 and 4 weeks after the
end of treatment. Concentrations of elvucitabine in plasma will be measured on Day 1, at
Weeks 4, 6, 8, 12, 16, 24, 48, 72, 96, and at Follow-up

Efficacy will be assessed by measuring plasma HIV-1 RNA levels and CD4 counts at each study
visit.

Safety evaluation will include vital signs, physical examinations, electrocardiograms,
assessments of adverse events (AEs), measurement of plasma HIV-1 RNA levels and CD4 counts,
determination of HIV-1 genotype at Screening, and at Weeks 12, 24, 48 and 96 determination
of HIV-1 phenotype at Visit 1 and at Weeks 12, 24, 48, and 96 urine and serum pregnancy
tests, as well as laboratory analyses that include hematology, chemistry, and urinalysis.

Inclusion Criteria:

A subject must meet the following criteria at Screening to be enrolled in this study:

1. Are male or female. Sexually active men with partners of childbearing potential must
agree to use an acceptable form of contraception as determined by the investigator
(eg, oral contraceptives, double-barrier methods, hormonal injectable or implanted
contraceptives, tubal ligation, or vasectomy) during participation in the study.
Female subjects cannot be pregnant or lactating/breast-feeding and must be surgically
sterile, postmenopausal as defined later, or practicing an effective method of birth
control as determined by the investigator (eg, oral contraceptives, double-barrier
methods, hormonal injectable or implanted contraceptives, tubal ligation, or partner
with vasectomy). A woman may be considered postmenopausal if she is at least 50 years
or older, has a history of no menses for at least 12 months, and has an follicle
stimulating hormone (FSH) level over the upper limit of normal for reproductive aged
women.

2. Are 18 through 65 years old

3. Have documented HIV-1 infection by written prior history and clinically stable with
no AIDS-defining events in the 3 months prior to Screening

4. Have plasma HIV-1 RNA levels greater than or equal to 5000 copies/mL at Screening

5. Are HIV-1 strain sensitive to elvucitabine, lamivudine, emtricitabine as demonstrated
by the absence of the M184V, M184I, and D237E mutations by TRUGENE HIV-1 Genotyping
Kit

6. Are HIV-1 strain genotypically sensitive to efavirenz (negative for K103 and Y188L
mutations) and tenofovir (negative for K65R mutation) by TRUGENE HIV-1 Genotyping Kit

7. Have a CD4 count greater than or equal to 200 cells/mL and less than 500 cells/mL

8. Have acceptable hematologic and chemistry parameters, including the following:

- Hemoglobin (Hgb) greater than or equal to 11g/dL

- Absolute neutrophil count greater than or equal to 2000 cells/mm3

- Platelets greater than or equal to 125 000/mm3

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or
equal to 1.5 times the upper limit of normal

- Total bilirubin less than or equal to 1.5 times the upper limit of normal

- Creatinine within normal range

9. Are capable of understanding and has signed the informed consent document

10. Are able and willing to comply with protocol requirements

Exclusion Criteria:

Subjects meeting any of the following criteria at Screening will be excluded from the
study:

1. Are hepatitis B surface antigen positive, and/or hepatitis B virus (HBV) DNA positive

2. Have previous therapy with agents with significant systemic myelosuppressive or
cytotoxic potential within the 3 months prior to Screening or the expected need for
such therapy during the study

3. Have previous use or need for bone marrow colony-stimulating factors such as Epogen,
Procrit, or Neupogen

4. Have had previous antiretroviral therapy

5. Have evidence or history of cirrhosis

6. Have recent (within 3 months of Screening) history of alcohol abuse, physical
dependence to any opioid, cocaine, LSD or amphetamines, or history of drug addiction
within the last 12 months

7. Have inability to tolerate oral medication

8. Are pregnant or breast-feeding if female

9. Have any clinical condition or prior therapy that, in the investigator's opinion,
would make the subject unsuitable for the study or unable to comply with the dosing
requirements

10. Have received treatment with any other investigational drug within 30 days prior to
Screening

11. Have current active mental illness or a history of significant mental illness (eg,
severe depression, schizophrenia, history of suicidal ideations, or suicide
attempts).