TNX-355 With Optimized Background Therapy (OBT) in Treatment-Experienced Subjects With HIV-1

Subjects must have all of the following to be included in the study:

• Triple-class experience, with no minimum exposure to any class (historical exposure to NRTI, NNRTI, PI)
• Cumulative HAART experience for a minimum of 6 months
• Virus susceptibility to one or more antiretroviral drugs in their selected OBT as determined by the PhenoSenseGT or similar assay and medication history
• Stable plasma HIV-1 RNA levels quantitated by reverse-transcriptase polymerase chain reaction (RT-PCR) of 10,000 copies/mL within 8 weeks prior to randomization (Day 1), while receiving a stable HAART regimen for a minimum of 4 weeks prior to screening. Stable viral load is defined as a difference of 0.5-log10 in HIV-1 RNA copies/mL from two measurements obtained at least 48 hours apart during the screening period
• Subjects must be failing their current HAART regimen or have discontinued a failing HAART regimen within 8 weeks prior to screening (screening visit 1)
• CD4+ cell count 50 cells/mL
• If sexually active, willingness to use an effective, medically accepted (including barrier) method of contraception during the study. To prevent superinfection, any male subject and the male sexual partner of any study subject should use a condom. All study subjects and all of their sexual partners should practice additional safe sex techniques to prevent spread of HIV.

Exclusion Criteria:

Subjects with any of the following characteristics will be excluded from the study:

• Any significant diseases (other than HIV infection) or clinically significant findings, including psychiatric and behavioral problems, medical history and/or physical examination, determined from screening, that, in the investigator's opinion, would preclude the subject from participating in this study
• Acute illness within one week prior to administration of study drug (including diarrhea and/or vomiting and fever and/or other signs and symptoms of infection such as leukocytosis, etc.)
• Any active infection secondary to HIV, requiring acute therapy. However, subjects that require maintenance therapy (i.e. secondary prophylaxis for opportunistic infections) will be eligible for the study
• Any immunomodulating therapy or systemic chemotherapy within 12 weeks prior to randomization (Day 1)
• Any investigational drug use within 30 days prior to randomization (Day 1). This does not include investigational drugs for the treatment of HIV-1 (NRTI, NNRTI or PI) under expanded access. OBT may include drugs not currently approved, but prescribed under expanded access (limited to NRTI's, NNRTI's and PI's).
• Any prior participation in an HIV vaccine study
• Opportunistic infections (OIs) in the previous 12 weeks prior to randomization (Day 1)
• Any prior exposure to TNX-355 (Hu5A8)
• Vaccination within 21 days (3 weeks) prior to randomization (Day 1)
• Any previous exposure to any virus/fusion entry inhibitor/s
• Any previous exposure to a monoclonal antibody (prior treatment with hepatitis B immune globulin [HBIG] or intravenous immune globulin [IVIG] is acceptable)
• Life expectancy of less than 12 months
• Female subjects who are either pregnant or breastfeeding
• Any illicit intravenous drugs within 6 months prior to randomization (Day 1)
• Any current alcohol or illicit drug use that, in the investigator's opinion, will interfere with the subject's ability to comply with the dosing schedule and protocol evaluations

• Clinically significant laboratory findings obtained during screening including:

  • Serum creatinine or BUN (>1.5 X Upper Limit of Normal [ULN])
  • Alkaline phosphatase, aspartase aminotransferase (AST), alanine aminotransferase (ALT) (any > 2.5 [ULN])
  • Total bilirubin (>1.5 ULN)
  • Pancreatic amylase and/or lipase (>1.5 ULN)
  • Hemoglobin (\<9.0 g/dL for males; \< 8.0 g/dL for females)
  • Platelet Count (\<75,000 x 106/L)
  • Absolute Neutrophil Count (\< 1,000 X 106/L)