Immunologic Response to Kansui in Treated HIV+ Individuals: a Dose Escalation Study

• Status: Suspended
• Trial end date: 2022-06-30
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to determine the safety and bioactivity of an herbal supplement called "kansui," which contains several active ingredients such as ingenols that may have a role in helping clear HIV from the body. Kansui has been used in traditional Chinese medicine for centuries to treat various ailments such as for eliminating excess fluid in the abdomen or lungs, loosening phlegm from the chest, and relieving constipation. Based on preliminary in vitro data from our group, kansui extract powder is a potent activator of HIV transpcription in latently infected Jurkat cells. The investigators' hypothesis is that kansui extract powder prepared as tea will be safe and well-tolerated, elicit an in vivo immunologic response, and at the doses administered, increase HIV transcription in latently-infected cells among HIV-infected patients on suppressive antiretroviral therapy.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of California, San Francisco
• Collaborators: amfAR, The Foundation for AIDS Research; Center for AIDS Research (CFAR); University of Utah

Criteria

Inclusion Criteria:

1. Confirmed HIV-1 infection in adults aged 18 years or older.

2. Continuous therapy with a DHHS recommended/alternative combination ART for least 36 months (at least 3 agents) at study entry with no regimen changes in the preceding 24 weeks.

3. Maintenance of undetectable plasma HIV-1 RNA (<40 copies/ml) for at least 36 months. Episodes of single HIV plasma RNA 50-500 copies.ml will not exclude participation if subsequent HIV plasma RNA is <40 copies/ml.

4. Two CD4+ T cell counts >350 cells/μl in the six months prior to screening.

Exclusion Criteria:

1. Pre-ART viral load <2000 copies/ml (HIV controllers)

2. Based on prior history and/or virologic testing, no alternative ART regimens are available in the event that the current ART regimen is compromised as a result of this study.

3. Recent hospitalization in the last 90 days.

4. Recent infection in the last 90 days requiring systemic antibiotics.

5. Recent vaccination within the last 8 weeks prior to study scree or any study blood draw.

6. Any known history of liver-related diseases including but not limited to: hepatic cirrhosis of decompensated chronic liver diseases; clinically active hepatitis B or C infection as evidenced by clinical jaundice or Grade 2 or higher liver function test abnormalities; any hepatic impairment, regardless of the graded liver function test abnormalities.

7. Any known history of gastrointestinal diseases including but not limited to: history of diarrheal illness requiring the use of anti-motility agents including inflammatory bowel disease, chronic diarrhea not otherwise specified; history of gastrointestinal bleeding with hemoglobin below 12.5 g/dL; history of gastric or duodenal ulcers; inflammatory gastrointestinal disease such as Crohn's disease or ulcerative colitis

8. Any renal disease (eGFR < 90 ml/min) or acute nephritis.

9. Screening hemoglobin below 12.5 g/dL.

10. Screening TSH consistent with hypothyroidism.

11. Significant myocardial disease (current myocarditis or reduced left ventricular ejection fraction below the lower limit of normal) or diagnosed coronary artery disease.

12. Significant respiratory disease requiring oxygen.

13. Diabetes or current hypothyroidism.

14. Participants of reproductive potential or breastfeeding. Women of childbearing potential must have a negative serum pregnancy test at screening. All participants of childbearing potential must agree to use a double-barrier method of contraception throughout the study period and up to 90 days after the last dose of kansui.

15. Exposure to any immunomodulatory drug (including maraviroc) in the16 weeks prior to study.

16. Prior or current use of experiment agents used with the intent to perturb the HIV-1 viral reservoir.

17. History of seizures, psychosis, abnormal electroencephalogram or brain damage with significant persisting neurological deficit

18. Positive test for tuberculosis by either skin test (PPD) or blood interferon-gamma release assay (QuantiFERON).

19. Significant substance use, which in the opinion of the investigator(s), is likely to interfere with the conduct of the study.