Clinical Trial of CNS-targeted HAART (CIT2)
Summary
CIT2 is a strategy for targeting HAART (Highly Active Antiretroviral Therapy) to the CNS (Central Nervous System) in patients with HIV associated neurocognitive impairment (HNCI). The primary goal of this study is to evaluate the effectiveness of CNS-targeted (CNS-T) as compared to non-CNS-targeted (non-CNS-T) HAART in treating HNCI globally and in different domains of functioning known to be affected by HIV. It is hypothesized that participants in the CNS-T arm will have greater improvement in neurocognitive functioning than those in the non-CNS-T arm. The secondary goal of the study is to compare participants assigned to CNS-T and non-CNS-T HAART on measures of CNS and systemic HIV suppression (undetectable CSF and plasma VL). It is also hypothesized that although CSF viral suppression will be more frequent in the CNS-T arm, plasma viral suppression will be similar in the two treatment arms.
Timeline
- Start
- 2007-03
- Primary completion
- 2012-02
- Completion
- 2012-06
Outcome
Missed primary endpoint
paper The proportional improvement in GDS from baseline was nonsignificantly larger (7%; 95% confidence interval [CI], -31% to 62%) PMID 24352352 ↗
paper CONCLUSIONS: This study found no evidence of neurocognitive benefit for a CNS-T strategy in HIV-associated neurocognitive disorders. PMID 24352352 ↗
Publications
- Background May S, Letendre S, Haubrich R, McCutchan JA, Heaton R, Capparelli E, Ellis R. Meeting practical challenges of a trial involving a multitude of treatment regimens: an example of a multi-center randomized controlled clinical trial in neuroAIDS. J Neuroimmune Pharmacol. 2007 Mar;2(1):97-104. doi: 10.1007/s11481-006-9057-8. Epub 2007 Jan 10.
- Background Letendre 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.
- Results Ellis RJ, Letendre S, Vaida F, Haubrich R, Heaton RK, Sacktor N, Clifford DB, Best BM, May S, Umlauf A, Cherner M, Sanders C, Ballard C, Simpson DM, Jay C, McCutchan JA. Randomized trial of central nervous system-targeted antiretrovirals for HIV-associated neurocognitive disorder. Clin Infect Dis. 2014 Apr;58(7):1015-22. doi: 10.1093/cid/cit921. Epub 2013 Dec 18.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Abacavir | Other / unclassified | — | — |
| Subject | Amprenavir | Other / unclassified | — | — |
| Subject | Atazanavir | Other / unclassified | — | — |
| Subject | Darunavir | Small molecule | — | — |
| Subject | Delavirdine | Small molecule | — | — |
| Subject | Efavirenz | Other / unclassified | — | — |
| Subject | Enfuvirtide | Peptide | — | — |
| Subject | Etravirine | Small molecule | — | — |
| Subject | Fosamprenavir | Small molecule | — | — |
| Subject | Lamivudine | Other / unclassified | — | — |
| Subject | Lopinavir | Other / unclassified | — | — |
| Subject | Maraviroc | Other / unclassified | — | — |
| Subject | Nelfinavir | Other / unclassified | — | — |
| Subject | Nevirapine | Small molecule | — | — |
| Subject | Raltegravir | Other / unclassified | — | — |
| Subject | Ritonavir | Other / unclassified | — | — |
| Subject | Saquinavir | Small molecule | — | — |
| Subject | Tenofovir | Small molecule | — | — |
| Subject | Tipranavir | Small molecule | — | — |
| Subject | Zidovudine | Small molecule | — | — |
| Subject | emtricitabine | Other / unclassified | — | — |