Study of Valproic Acid to Treat HIV Infected Adults

What Was Tested

In this phase 1 trial, researchers set out to test Enfuvirtide.

A histone deacetylase (HDAC) inhibitor is a class of drug that interferes with the function of HDAC, an enzyme that hides HIV within inactive CD4 cells.

These drugs are normally used to treat seizures and other nervous system problems but have been found to work against HIV.

It had four arms (groups): 2A (experimental), 2B (experimental), 3A (experimental) and 3B (experimental).

Discontinuation of VPA and enfuvirtide administered for 24 weeks. As of 05/20/08 this step was discontinued.

Continuation of VPA for up to 96 weeks. As of 05/20/08 this step was discontinued.

VPA may be added to enfuvirtide for 16 weeks. VPA and enfuvirtide will be continued for up to 96 weeks in responders, and the study will be discontinued in nonresponders.

The registry classes the interventions as drug.

More on the Plan

VPA is a type of medication normally used to treat seizures and other nervous system problems.

The expected duration of participation for individually enrolled participants will depend on which study group the participant is placed in but may range from approximately 24 to 144 weeks.

An initial screening visit will occur about 30 to 120 days prior to study entry.

A physical exam, medical and medication history assessment, and blood and urine collection will occur at screening.

Who Took Part

The registry lists 14 actual participants took part.

It was open to people of any sex aged from 18 years with no upper age limit.

Healthy volunteers were not accepted; participants needed the condition being studied.

Examples of who could join: Adherent to current HAART regimen. Adequate vascular access for leukapheresis. CD4 count more than 300 cells/mm3. Willing and able to comply with all study requirements. Willing to use acceptable forms of contraception.

The full record lists 8 inclusion and 16 exclusion criteria; among the exclusions: currently receiving zidovudine or enfuvirtide; require certain medications known to interact with valproate (e.g., lamotrigine; barbiturates; carbamazepine; prescription dosages of salicylates, hydantoins, felbamate, and clonazepam); any medical, psychiatric, or job-related responsibility that would interfere with the study. more information about this criterion can be found in the protocol.

How the Study Was Run

Design: non-randomized, crossover and open-label.

In the crossover set-up each of the participants took both Enfuvirtide and the comparison in turn, acting as their own control.

Everyone knew when Enfuvirtide was being given (open label), which is simpler to run but leaves more room for expectations to affect what is reported.

It started in 2006-06 with completion listed for 2009-04.

It ran at 1 site in United States.

Its stated primary purpose is treatment.

What Was Measured

Researchers chose this as the main measure: Frequencies of replication-competent HIV detected in resting CD4 cells (time frame: At pre-entry and Week 0 to Weeks 12 and 16).

It also tracked 6 secondary outcomes, for example Change in integrated proviral genomes, Genital tract proviral DNA and viral load, Detectable viral load during VPA therapy and if it remains undetectable after VPA is discontinued, HIV-specific antibody changes and CTL responses and Changes in viral load after intensification of HAART with or without VPA.

What This Means in Plain Language

Put simply, this is a phase 1, non-randomized trial of Enfuvirtide in 14 people.

Its size is small, so on its own it can only give an early look.

It ended early (terminated); no results are posted to the registry yet, so nothing here describes outcomes.

More context: the Enfuvirtide compound page, all human trials.