An Interaction Study to Assess Drug Levels in Healthy Adult Subjects

This randomized, open-label, six-arm, three-period drug interaction study will recruit 48
healthy volunteers so as to obtain a minimum of 36 evaluable subjects at a single study
center in the U.S. The study will have a screening visit, 3 treatment visits for PK sampling
and a follow-up visit. The screening visit will be conducted within 30 days prior to
receiving the first dose. Subjects will then be randomized into 1 of 6 treatment groups as
shown below:

Cohort Size Period 1 Days 1 to 7 Period 2 Days 1-14 Period 3 Days 1-14

A 8 MVC 300mg BID; FPV 1400mg BID; FPV 1400mg BID & MVC 300mg BID

B 8 MVC 300mg BID; FPV 1400mg BID & MVC 300mg BID; FPV 1400mg BID

C 8 MVC 300mg BID; FPV 700mg BID & RTV 100mg BID; FPV 700mg BID & RTV 100mg BID &MVC 300mg
BID

D 8 MVC 300mg BID; FPV 700mg BID & RTV 100mg BID & MVC 300mg BID; FPV 700mg BID & RTV 100mg
BID

E 8 MVC 300mg BID; FPV 1400mg QD & RTV 100mg QD; FPV 1400mg QD & RTV 100mg QD & MVC 300mg
BID

F 8 MVC 300mg BID; FPV 1400mg QD & RTV 100mg QD & MVC 300mg BID; FPV 1400mg QD & RTV 100mg
QD

Study subjects will enter the clinic in the morning prior to dosing and remain at the center
for 12 hours following each dose. Fourteen to 21 days following completion of the third
dosing period, study subjects will return to the clinic for follow-up assessment. The total
duration of the study will be approximately 86 days from screening through follow up. Blood
samples for drug concentration measurement of amprenavir (APV) and maraviroc(MVC)
concentrations will be collected over 12 hours at the end of each dosing period (at 0
[baseline], 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose). Subjects will undergo a
physical examination, CBC with differential, HIV test, hepatitis B/C test, liver function
test, renal function analysis, and lipid panel at screening, and all of these tests except
those for HIV and hepatitis B/C will be repeated at follow-up post-study. Adverse events and
adherence (by pill count and medication diary) will be assessed by the investigator/study
personnel at the end of each dosing period. Evaluable patients will be required to have
adhered to at least 95% of their study drug doses. Plasma APV and MVC concentrations will be
analyzed using a validated high-performance liquid chromatography method with tandem mass
spectrometric detection (HPLC/MS/MS). Plasma APV and MVC pharmacokinetic parameters measured
will include maximum concentration (Cmax), time to maximum concentration (Tmax), minimum
concentration (Cmin), and area under the concentration-time curve (AUC). All these
parameters, except Tmax, will be log-transformed before statistical analysis. Analysis of
variance, considering treatment as a fixed effect and subject as a random effect will be
performed using Statistical Analysis Software (SAS), and assuming a treatment ratio for
steady-state APV PK parameters as 1.0, the 90% confidence intervals will be within the range
0.81-1.24.

Inclusion Criteria:

- Healthy subjects with no clinically significant abnormality identified by physician
by evaluation of medical history, physical examination, clinical laboratory tests or
vital signs.

- between 18 and 64 years,

- A female subject is eligible to participate if she is neither pregnant nor
lactating, and falls into one of the following categories:

- non-childbearing potential including females with documented (medical report
verification) hysterectomy or bilateral oophorectomy, or post-menopausal females
defined as being amenorrheic for greater than 1 year and having estradiol and
follicle stimulating hormone (FSH) levels consistent with menopause.

- child-bearing potential with a negative serum pregnancy test at screen and who
agrees to use one of the following methods of contraception from screening or at
least two weeks prior to the first dose (whichever is earlier) until the
follow-up visit (any contraception method must be used consistently and
correctly, i.e., in accordance with both the product label and the instructions
of a physician).

- Agreement for complete abstinence from intercourse

- Double barrier contraception (male condom/spermicide, male
condom/diaphragm, diaphragm/spermicide)

- Any intrauterine device (IUD) with published data showing that the expected
failure rate is less than 1% per year (not all IUDs meet this criterion)

- Any other method with published data showing that the lowest expected
failure rate for that method is less than 1% per year.

- Adequate renal function (calculated creatinine clearance via Cockcroft and Gault
method (CrCl) > 50 mL/min);

- Adequate hepatic function (total bilirubin < 2.5mg/dL; hepatic transaminases <
5x normal);

- Adequate hematologic function (absolute neutrophil count [ANC] > 750
neutrophils/mm^3; platelets > 50,000/mm^3; hematocrit > 25%);

- Non-smoker, defined as not having used nicotine-containing products within the
past 6 months.

- Willingness and ability to adhere to treatment and follow-up procedures;

- The ability to understand and sign a written informed consent form.

- Body weight > or =50 kg for males and > or=45 kg for females and body mass index
(BMI) in the range of 19 to 30 kg/m^2 (BMI = weight [kg]/(height [m])^2).

Exclusion Criteria:

- • Have an active infection that required parenteral antibiotics or hospitalization
within 2 weeks prior to enrollment;

- A history of or documented gastrointestinal diseases that impact drug
absorption;

- Have a significant documented sulfa allergy (e.g., Stevens-Johnson Syndrome) or
a history of sensitivity to any of the study medications, or components thereof;

- HIV, Hepatitis B or C positive

- Cigarette/cigar/pipe smokers;

- History of alcohol/drug abuse or dependence within 12 months of the study, or a
history of alcohol consumption in the past six months exceeding 7 units/week for
women and 14 units/week for men (where 1 unit = 5 ounces of wine or 12 ounces of
beer or 1.5 ounces of hard liquor).

- Treatment with an investigational drug within 30 days or 5 half-lives (whichever
is longer) preceding the first dose of study medication.

- Use of prescription or non-prescription drugs (including aspirin and
nonsteroidal antiinflammatory drug (NSAIDs), vitamins, herbal and dietary
supplements within 7 days (or 14 days if the drug is a potential enzyme inducer,
such as St. John's Wort) or 5 half-lives (whichever is longer) prior to the
first dose of study medication, unless in the opinion of the investigator the
medication will not interfere with the study procedures or compromise subject
safety.

- Subjects who have donated plasma within 7 days prior to the screening visit or
where participation in this study would result in donation of blood in excess of
500 mL of blood within 56 day period.