Recombinant Human Interleukin-7 (JL18008) for the Treatment of HIV-Infected Immunological Non-Responders

Prior treatment

• Prior treatment with IL-7 or IL-2.
• Prior treatment with immunomodulatory agents such as thymosin, immunosuppressive drugs, or cytotoxic chemotherapy within 6 months prior to study entry.
• Any history of virus, bacteria, parasites or fungal infection and other opportunistic infections requiring systemic treatment and/or hospitalization within 30 days prior to study entry.
• Active tuberculosis within 30 days prior to study entry.
• Severe cardiovascular disease: myocardial infarction, unstable angina pectoris, symptomatic congestive heart failure (New York Heart Association \> class II) or cardiac arrhythmia requiring medication within 6 months prior to study entry.
• Diagnosis of cancer within the last 5 years prior to study entry (except skin basal cell or squamous cell carrcinomas, and cutaneous Kaposi's sarcoma not requiring systemic therapy).
• History of drug abuse (e.g. heroin, cocaine, and crystal meth, etc.) or alcohol abuse (defined as the daily regular consumption of alcohol exceeding the following standard amount: 570 ml of beer, 750 ml of light beer, 200 ml of red wine or 60 ml of liquor, each containing about 20 g of alcohol) within 3 months prior to study entry and heavy smoker (over 20 cigarettes per day for more than 3 months) within 6 months prior to study entry.
• Treatment with another study drug within 3 months prior to study entry.
• History of vaccination with live attenuated vaccine in 6 weeks prior to study entry or vaccination planed during the study and within 3 months after completion of the study.

Other illness

• Allergy to JL18008 Injection components, e.g. HSA.
• Any history of generalized psoriasis, Crohn's disease, uveitis, systemic lupus erythematosus (SLE), Hashimoto's thyroiditis or other autoimmune diseases.
• Any hematologic disease associated with hypersplenism, such as thalassemia, hereditary spherocytosis, Gaucher's Disease, and autoimmune hemolytic anemia.
• History of splenectomy.
• Any gastrointestinal illness associated with chronic or intermittent diarrhea.
• Hypertension with a resting systolic blood pressure \> 140 mmHg or a resting diastolic blood pressure \> 90 mmHg despite adequate antihypertensive treatment.
• Hepatitis B Surface Antigen (HBs Ag) positive and/or Hepatitis C virus (HCV) antibody positive and HCV-RNA positive.
• Any history of HIV related encephalopathy.
• Any history of severe mental disorders or epilepsy.
• History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or sponsor physician would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.

Lab values

• Abnormal clinical laboratory tests results meet any of the following criteria: Hemoglobin (HGB) \< 120 g/L for men and \< 110 g/L for women; White blood cell (WBC) count \< 3.5 × 109/L; neutrophil count (NEUT) \< 1.5 × 109/L; Platelet (PLT) count \< 125 × 109/L; Creatinine (Cr) \> 1.1 × upper limit of normal value (ULN); Alanine aminotransferase (ALT) \> 1.1 × ULN; Aspartate aminotransferase (AST) \> 1.1 × ULN; Alkaline phosphatase (ALP) \> 1.1 × ULN; Total bilirubin (TBIL) \>1.1 × ULN; Phosphate level \< 2.5 mg/dL; International normalized ratio (INR) \> 1.3; Activated partial thromboplastin time (APTT) \< 1.5 × ULN.

Other

• Pregnancy or lactation.

• Age between 18 - 65 years old, male or female.
• Body Mass Index (BMI) between 18 - 32 kg/m2, body weight ≥ 50 kg in male and ≥ 45 kg in female.
• On cART for at least 36 months, on stable regimen (no drug or dose changes) for at least 3 months prior to study entry.
• Plasma HIV RNA \< 50 copies/mL in last 30 months in minimum two measurements (including the screening measurement) and the two measurements should done within 6 months prior to study entry (note: patients with single blip of detectable viremia during this period will be allowed to participate if the prior and subsequent plasma HIV RNA levels are \< 50 copies/mL).
• During 12 months prior to study entry, CD4+ T cell counts \> 100 and ≤ 350 cells/µL measured in at least two measurements (including the screening measurement) and the interval between the two measurements should be ≥ 3 months (Note: only one time value of CD4+ T cell count \> 350 during this period will be allowed to participate if the previous and subsequent CD4+ T cell count is in the range of \> 100 and ≤ 350 cells/µL).
• All subjects must agree not to participate in the conception process (e.g. active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization), and if participating in sexual activity that could lead to pregnancy, the subject/partner must practice at least one form of barrier birth control (condoms, with or without spermicidal agent, a diaphragm or cervical cap with spermicide, an IUD, other barrier contraception, etc.), during study and 3 months after the study.
• The subject fully understands the requirements of the study and voluntarily signs the ICF.