Ibalizumab Plus Optimized Background Regimen in Patient With Multi-Drug Resistant HIV

This Phase 3, single arm, multicenter study will evaluate the safety and effectiveness of
ibalizumab in treatment-experienced patients infected with multi-drug resistant HIV-1.
Patients must have been treated with HAART for at least 6 months and be failing or have
recently failed (i.e., in the last 8 weeks) therapy to determine baseline viral load.

Days 0-6 of the study will be a "control period." During Days 0 through 6 patients will be
monitored on current failing therapy (or no therapy, if the patient has failed and
discontinued treatment within the 8 weeks preceding Screening).

Days 7-13 of the study will be an "essential monotherapy period." During Days 7 through 13
patients will continue on current failing therapy and receive one 2000 mg dose (loading
dose) of ibalizumab on Day 7. Day 7 is Baseline for the treatment period (Day 7-Week 25).

Day 14-Week 25 of the study will be the "maintenance period." On Day 14 (primary endpoint),
the OBR will be initiated and must include at least one agent to which the patient's virus
is susceptible. Beginning at Day 21, 800 mg of ibalizumab will be administered every 2 weeks
through Week 23.

End of Study evaluations will be performed at Week 25, and a follow-up visit will be
conducted at Week 29.

Inclusion Criteria:

- Are capable of understanding and have voluntarily signed the informed consent
document

- Have documented HIV-1 infection by official, signed, written history (e.g.,
laboratory report), otherwise an HIV-antibody test will be performed

- Have no acquired immunodeficiency syndrome (AIDS)-defining events in the 3 months
before Screening, other than cutaneous Kaposi's sarcoma or wasting syndrome due to
HIV

- Are able and willing to comply with all protocol requirements and procedures

- Have a life expectancy that is >6 months.

- Have a viral load >1,000 copies/mL and documented resistance to at least one
antiretroviral medication from each of three classes of antiretroviral medications as
measured by resistance testing

- Have a history of at least 6 months on antiretroviral treatment

- Are receiving a stable highly active antiretroviral regimen for at least 8 weeks
before Screening and are willing to continue that regimen until Day 14, OR (in the
past 8 weeks) have failed and are off therapy and are willing to stay off therapy
until Day 14

- Have full viral sensitivity/susceptibility to at least one antiretroviral agent,
other than ibalizumab, as determined by the screening resistance tests and be willing
and able to be treated with at least one agent to which the patient's viral isolate
is fully sensitive/susceptible according to the screening resistance tests as a
component of OBR

- If sexually active, are willing to use an effective method of contraception during
the study and for 30 days after the last administration of the study drug

Exclusion Criteria:

- Any active AIDS-defining illness per Category C conditions according to the Centers
for Disease Control and Prevention (CDC) Classification System for HIV Infection,
with the following exceptions: cutaneous Kaposi's sarcoma and wasting syndrome due to
HIV

- Any significant diseases (other than HIV-1 infection) or clinically significant
findings, including psychiatric and behavioral problems, determined from screening,
medical history and/or physical examination that, in the investigator's opinion,
would preclude the patient from participating in this study

- Any significant acute illness within 1 week before the initial administration of
study drug

- Any active infection secondary to HIV requiring acute therapy; however, patients that
require maintenance therapy (i.e., secondary prophylaxis for opportunistic
infections) will be eligible for the study.

- Any immunomodulating therapy (including interferon), systemic steroids, or systemic
chemotherapy within 12 weeks before Enrollment

- Any prior exposure to ibalizumab (formerly TNX-355 and Hu5A8)

- Any vaccination within 7 days before Enrollment

- Any female patient who either is pregnant, intends to become pregnant, or is
currently breastfeeding

- Any current alcohol or illicit drug use that, in the investigator's opinion, will
interfere with the patient's ability to comply with the study schedule and protocol
evaluations

- Any previous clinically significant allergy or hypersensitivity to any excipient in
the ibalizumab formulation

- Any radiation therapy during the 28 days before first administration of
investigational medication

- Any Grade 3 or 4 laboratory abnormality according to the Division of AIDS grading
scale, except for the following asymptomatic Grade 3 events triglyceride elevation
total cholesterol elevation