Clinical Trial of Brain-Penetrating HIV Drugs to Prevent Cognitive Impairment in China
Clinical Trial of CNS Penetrating ART to Prevent NeuroAIDS in China
2 other identifiers
interventional
250
1 country
2
Brief Summary
This primary aim of the project is to determine the association between antiretroviral therapy that better distributes into the central nervous system and prevention of HIV-associated neurocognitive impairment.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4 hiv-infections
Started Jul 2010
Longer than P75 for phase_4 hiv-infections
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
July 1, 2010
CompletedFirst Submitted
Initial submission to the registry
April 21, 2011
CompletedFirst Posted
Study publicly available on registry
April 25, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
July 1, 2015
CompletedApril 4, 2016
March 1, 2016
4 years
April 21, 2011
March 31, 2016
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Decline in neuropsychological performance at 96 weeks
Comparison of decline in NP performance between treatment groups.
96 weeks
Study Arms (2)
Better-Penetrating ART
ACTIVE COMPARATORzidovudine 300 mg orally every 12 hours lamivudine 300 mg orally daily nevirapine 200 mg orally every 12 hours
Worse-Penetrating ART
ACTIVE COMPARATORtenofovir disoproxil fumarate 300 mg orally daily lamivudine 150 mg orally every 12 hours efavirenz 600 mg orally daily
Interventions
96 weeks of zidovudine 300 mg orally twice daily, lamivudine 300 mg orally daily, nevirapine 200 mg orally daily for the first 14 days then 200 mg orally twice daily
96 weeks of tenofovir disoproxil fumarate 300 mg orally daily, lamivudine 300 mg orally daily, efavirenz 600 mg orally daily
Eligibility Criteria
You may qualify if:
- Men and women of at least 18 years of age.
- Ability and willingness of subject to give written informed consent.
- HIV-1 infection, as documented by enzyme-linked immunosorbent assay (ELISA) and confirmed by Western blot at any time prior to study entry. Plasma HIV-1 RNA is acceptable as an alternative confirmatory test.
- Antiretroviral drug-naïve, defined as ≤10 days of ART at any time prior to entry.
- Clinical HIV-1 RNA ≥1000 copies/mL obtained within 90 days of study screening.
- Clinical blood CD4+ cell count \< 350/mm3 (for men) or \<250/mm3 (for women) within 60 days of study screening.
- Performance within the expected normal range on the project's comprehensive, standardized battery of neuropsychological tests within 4 weeks.
- For women of child-bearing potential (WOCBP), negative serum or urine pregnancy test at screening and within 48 hours prior to initiating study medications.
You may not qualify if:
- Serious illness requiring systemic treatment or hospitalization within 4 weeks.
- Unacceptable laboratory values obtained within 4 weeks prior to study entry.
- Untreated syphilis.
- Child Pugh Class C hepatic impairment.
- Active Hepatitis B Virus infection.
- Known allergy/sensitivity to study drugs or their formulations.
- Severe or untreated conditions that could affect NP test performance.
- Such conditions include but are not limited to current substance use disorder, poorly controlled diabetes, uncontrolled seizure disorder, and any progressive CNS disorder (e.g., multiple sclerosis, CNS neoplasm) and evidence of acute intoxication or withdrawal, in the opinion of the study clinician.
- Use of immunomodulators (e.g., interleukins, interferons, cyclosporine), HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy within 30 days prior to study entry.
- Currently breast-feeding.
- Requirement for any medications that have an absolute contraindication with any study drugs. In addition, we will exclude people taking rifampin.
- Current imprisonment or involuntary incarceration in a medical facility for psychiatric or physical illness.
- Prior use of nucleoside analogues, such as tenofovir, adefovir, or lamivudine, for treatment of hepatitis B for greater than 8 weeks while the subject was known to be HIV-infected.
- Any condition that, in the opinion of the investigators, would compromise the subject's ability to participate in the study.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of California, San Diegolead
- National Institute of Mental Health (NIMH)collaborator
- National Center for AIDS/STD Control and Prevention, China CDCcollaborator
- Beijing YouAn Hospitalcollaborator
- Beijing Ditan Hospitalcollaborator
- Peking Universitycollaborator
Study Sites (2)
Beijing Ditan Hospital
Beijing, Beijing Municipality, China
Beijing YouAn Hospital
Beijing, Beijing Municipality, China
Related Publications (5)
Heaton RK, Cysique LA, Jin H, Shi C, Yu X, Letendre S, Franklin DR, Ake C, Vigil O, Atkinson JH, Marcotte TD, Grant I, Wu Z; San Diego HIV Neurobehavioral Research Center Group. Neurobehavioral effects of human immunodeficiency virus infection among former plasma donors in rural China. J Neurovirol. 2008 Nov;14(6):536-49. doi: 10.1080/13550280802378880.
PMID: 18991068BACKGROUNDCysique LA, Letendre SL, Ake C, Jin H, Franklin DR, Gupta S, Shi C, Yu X, Wu Z, Abramson IS, Grant I, Heaton RK; HIV Neurobehavioral Research Center group. Incidence and nature of cognitive decline over 1 year among HIV-infected former plasma donors in China. AIDS. 2010 Apr 24;24(7):983-90. doi: 10.1097/QAD.0b013e32833336c8.
PMID: 20299964BACKGROUNDSpector SA, Singh KK, Gupta S, Cystique LA, Jin H, Letendre S, Schrier R, Wu Z, Hong KX, Yu X, Shi C, Heaton RK; HNRC Group. APOE epsilon4 and MBL-2 O/O genotypes are associated with neurocognitive impairment in HIV-infected plasma donors. AIDS. 2010 Jun 19;24(10):1471-9. doi: 10.1097/QAD.0b013e328339e25c.
PMID: 20442634BACKGROUNDLetendre S, Marquie-Beck J, Capparelli E, Best B, Clifford D, Collier AC, Gelman BB, McArthur JC, McCutchan JA, Morgello S, Simpson D, Grant I, Ellis RJ; CHARTER Group. Validation of the CNS Penetration-Effectiveness rank for quantifying antiretroviral penetration into the central nervous system. Arch Neurol. 2008 Jan;65(1):65-70. doi: 10.1001/archneurol.2007.31.
PMID: 18195140BACKGROUNDLetendre SL, McCutchan JA, Childers ME, Woods SP, Lazzaretto D, Heaton RK, Grant I, Ellis RJ; HNRC Group. Enhancing antiretroviral therapy for human immunodeficiency virus cognitive disorders. Ann Neurol. 2004 Sep;56(3):416-23. doi: 10.1002/ana.20198.
PMID: 15349869BACKGROUND
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Scott L Letendre, M.D.
University of California, San Diego
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Professor of Medicine
Study Record Dates
First Submitted
April 21, 2011
First Posted
April 25, 2011
Study Start
July 1, 2010
Primary Completion
July 1, 2014
Study Completion
July 1, 2015
Last Updated
April 4, 2016
Record last verified: 2016-03
Data Sharing
- IPD Sharing
- Will share
Data will be shared in conference presentations and peer-reviewed publications. Data will also be made available on approval of requests for appropriate use.