Eligibility |
Inclusion Criteria:
1. Male or female between 18-60 years
2. Documented HIV infection for =3 years
3. Suppression of HIV to <50 copies of viral RNA/mL plasma for =2 years. Participants who
had intermittent, isolated episodes of detectable low-level viremia (<500c/mL; blips)
will remain eligible. Participant must have a complete antiretroviral treatment
history including past and present data on resistance to antiretroviral therapy
4. Agree to continue their current antiretroviral regimen during the study period unless
change in treatment with antiretroviral regimen is medically indicated
5. Have, in the Investigator's opinion, a fully active alternative antiretroviral regimen
that can be used if resistance develops to the current antiretroviral therapy regimen
6. CD4 T cell count >400 cells/mm3
7. Has adequate organ function as indicated by the following laboratory values:
- Hematocrit =33% or hemoglobin =13g/dL (males) and =12g/dL (females)
- Platelet count =150,000/mm3
- Absolute neutrophil count =1,500/mm3
- Serum creatinine =1.3 times ULN or calculated creatinine clearance (for those
with creatinine >1.3 ULN) =60mL/min
- Prothrombin Time or INR = 1.5 times ULN
- Total bilirubin <1.5 times the ULN range. If total bilirubin is elevated, direct
bilirubin must be < 2 times the ULN range, except in participants with Gilbert's
Syndrome who must have serum bilirubin <3.0 times ULN (NOTE: If participant is on
an atazanavir containing therapy then a direct bilirubin should be measured
instead of the total bilirubin and must be = 1.0mg/dL. Also, asymptomatic
elevations due to ART medications are not exclusionary when, in the opinion of
the Investigator, the abnormalities are not attributable to intrinsic hepatic
disease).
- Amylase < 3 times ULN at the time of screening
- AST (SGOT) and ALT (SGPT): = 3.0 times ULN
8. Adequate venous access, per Investigator judgement, and no other contraindications for
leukapheresis
9. Weight (without shoes) =50 kilograms
10. Has the ability to understand the study and must be willing to comply with
study-required procedures and visits
11. Written informed consent signed and dated by the study participant
12. A negative pregnancy test for females of childbearing potential. A female participant
is considered to be of childbearing potential if she is menstruating, has an intact
uterus and at least 1 ovary, and is less than 2 years postmenopausal.
13. Unless medically prescribed, a negative drug test for amphetamines; barbiturates;
benzodiazepines; cocaine; methadone (Dolophine®); opiates (codeine, morphine only);
phencyclidine (PCP); propoxyphene
14. Agree to participate in the 15-year Long-Term Follow-Up study
Exclusion Criteria:
1. Active viral hepatitis B or hepatitis C infection. A complete hepatitis B virus (HBV)
screen (B-core antibody, HBV surface antibody, and HBV surface antigen testing) must
be completed. Viral load testing will be used in questionable cases, per the
discretion of the Investigator.
- The results for hepatitis B may be positive for surface antibodies against HBV
but must be negative for circulating HBV surface antigen to confirm the absence
of active infection and negative for HBV core antigen to excluded previous active
hepatitis
- The results for hepatitis C virus (HCV) may be positive for antibodies against
HCV but must be negative for HCV viral RNA in blood to confirm the absence of
active infection.
2. Liver disease by any cause
3. Active or history (within 5 years prior to screening) of at least one acquired immune
deficiency syndrome (AIDS)-defining complication
4. CD4 T cell nadir of <200 cells/mm3, if the information is available at the time of
screening per medical records. If this information is unavailable, the Investigator
will document this in the study source records
5. Cancer or malignancy that has not been in remission for at least 5 years prior to
screening, with the exception of successfully treated basal cell carcinoma of the skin
6. Current diagnosis of congestive heart failure, uncontrolled angina, or arrhythmias
7. Baseline prolonged QTc (Fridericia Formula) of 450 ms or more
8. Any clinically significant renal, hepatic, or pulmonary disease
9. History of active or latent tuberculosis, regardless of treatment history
10. Asplenia
11. Received high dose cytoreduction therapy within 3 months prior to screening
12. Currently taking (or has taken within 6 months prior to screening) the antiretroviral
drug Selzentry (Maraviroc)
13. Currently using protease inhibitors, efavirenz, or zidovudine
14. Prior events of hemorrhagic cystitis
15. Evidence of urinary outflow obstruction by history, enlarged prostate on physical
exam, or use of medications for urinary outflow obstruction
16. Is being treated for culture-confirmed bacteremia or had culture-confirmed bacteremia
within 1 month prior to screening
17. Has signs or symptoms of acute infectious disease
18. History of hereditary angioedema, acquired angioedema, or idiopathic angioedema
19. History of neurological diseases
20. Significant laboratory values and/or chronic medical condition that in the opinion of
the Investigator could impact trial participation
21. Received another investigational drug or device within 30 days of screening
22. Previously received any gene transfer therapy
23. History or any features on physical examination indicative of a bleeding diathesis
24. Use of aspirin, dipyridamole, warfarin and antithrombin inhibitors or any other
medication that is likely to affect platelet function or other aspects of blood
coagulation within 3 days prior to the Leukapheresis Visit
25. Use of chronic corticosteroids, hydroxyurea, or immunomodulating agents (e.g.,
monoclonal antibodies, interleukin-2, interferon-alpha or gamma, granulocyte colony
stimulating factors, etc.) within 30 days prior to screening (NOTE: Use of inhaled or
topical steroids is not exclusionary)
26. Currently pregnant or breast-feeding
27. Unwilling to use acceptable methods of birth control for 6 months following the
infusion of AGT103-T if sexually active with opposite sex. The following are
acceptable methods of birth control: condoms (male or female) with or without a
spermicidal agent, intrauterine device, diaphragm or cervical cap with spermicide, or
hormonal-based contraception
28. Active alcohol use or dependence that, in the opinion of the Investigator, would
interfere with adherence to study requirements
29. Serious illness requiring systemic treatment and/or hospitalization within 30 days
prior to screening
30. Recent vaccination or intercurrent illness within 5 weeks prior to screening (NOTE: It
is recommended that participants should have completed their routine vaccinations,
e.g., hepatitis A or B, pneumococcus, influenza and tetanus diphtheria booster, at
least 5 weeks prior to screening for the study)
31. Known allergy to Dimethyl Sulfoxide (DMSO)
32. Known allergy to Cyclophosphamide
|