Clinical trials for several types of therapeutic HIV vaccines are currently ongoing or recruiting participants.

Therapeutic HIV vaccines work by enhancing the body’s natural immune response, helping to control HIV in people already infected with the virus.

This is in contrast to preventative vaccines, which are used in HIV-negative individuals to prevent infection.

Researchers hope therapeutic vaccines will decrease dependence on antiretroviral drugs, which must be taken for life and often have serious side effects.

“A vaccine that enhanced the body’s ability to control HIV and delayed or decreased the dependence on anti-HIV drugs would be a major breakthrough for HIV treatment,” said Dr. Melanie Thompson, a lead investigator of one of the HIV vaccine trials.

No therapeutic vaccines are currently approved by the United States Food and Drug Administration.

DNA Vaccines

DNA vaccines contain pieces of DNA into which copies of several viral genes have been inserted. When human cells take up the DNA, they produce proteins encoded in the viral genes.

Researchers hope that the body’s immune system will recognize these proteins as harmful foreign agents and mount a powerful protective response.

DNA vaccines are a relatively new idea, and their effectiveness has not been well studied yet, although preliminary clinical trials have usually found them to be safe.

A small Phase 1 clinical trial investigating a therapeutic HIV DNA vaccine from GeoVax Labs is currently recruiting participants (pdf).

To be eligible for the GeoVax study, participants must have begun antiretroviral treatment within six months of diagnosis with HIV/AIDS. Additionally, individuals who have been HIV-positive for up to six months, but are yet to begin treatment, may be eligible for enrollment in the study.

Participants will be monitored to determine the safety of the vaccine and strength of their immune response for up to 77 weeks. For this initial study, only 10 to 12 people will be enrolled in the trial.

So far, studies in HIV-positive primates treated with the vaccine soon after infection gave good results. Clinical trials will now see if these results extend to HIV-infected humans as well.

Another Phase 1 DNA vaccine trial is also currently recruiting participants in London.

This trial, run by the Imperial College London and the Medical Research Council, will test a new therapeutic DNA vaccine coupled with immune-based therapy, which includes hormones and proteins called cytokines.

Immune-based therapies could help patients’ immune systems fight viruses on their own. Hormones and cytokines help regulate the immune system and can be used to induce, or prevent, growth and activity of particular cells in the immune system.

The researchers are especially interested in “why some people with HIV progress more slowly to disease and have longer survival without highly active antiretroviral therapy (HAART) than others.”

Their goal is to see if the vaccine plus immune-based therapy can create long-term nonprogressors, who are able to control the HIV virus for long periods of time without antiretrovirals.

The trial began in September 2009 and will investigate the safety and efficacy of the vaccine plus immune-based therapy for 52 weeks in approximately 30 HIV-positive individuals.

Study participants must be aged 18 or over with viral loads of less than 50 copies/milliliter and more than 400 CD4 cells/microliter.

Dendritic Cell Vaccines

Another novel vaccine type that will be tested in several new clinical trials is a dendritic cell vaccine, which is prepared using the participant’s own cells. Dendritic cell vaccines are considered to be very promising, because they are somewhat customized to each person.

To make a dendritic cell vaccine, researchers collect blood from participants and isolate a certain type of immune cell called a dendritic cell.

After exposing the cells to HIV proteins to prompt an immune response, the cells are reinjected into the study participant in hopes that they will now be activated and fight against HIV.

A Phase 1/2 clinical trial run by the University of Pittsburgh and the French National Agency for Research on AIDS and Viral Hepatitis (ANRS) is currently recruiting participants.

Eligible candidates must be at least 18 years of age with CD4 cell counts of at least 350 cells/microliter and HIV RNA levels between 5,000 and 100,000 copies/milliliter. Participants must also be antiretroviral therapy naïve.

Baylor Research Institute along with Baylor University and the ANRS are also organizing a Phase 1 clinical trial to assess the safety and efficacy of a dendritic cell vaccine in HIV patients on HAART.

The study, which began in November 2008, is currently recruiting participants and enrollment is estimated at 19 patients.

Participants must be 18 years or older and must have been on HAART for at least 12 months prior to enrollment. Additionally, participants must have CD4 cell counts of at least 500 cells/microliter and HIV RNA levels no greater than 50 copies/milliliter.

Protein Vaccines

Finally, there is a more traditional vaccine trial that is currently recruiting HIV-positive participants in Italy. Traditional HIV vaccines contain virus proteins that are injected into the participant in hopes of increasing immune response to the virus.

The Phase 2 trial in Italy will evaluate the safety and efficacy of an HIV Tat vaccine. Tat is an HIV protein released by infected cells that increases the rate of replication of the virus.

The study was initiated by the Instituto Superiore di Sanita in September 2008 and will enroll about 160 participants.

Participants must be between the ages of 18 and 55, must not possess anti-Tat antibodies, and must be on successful HAART with HIV viral concentrations of less than 50 copies/milliliter and at least 200 CD4 cells/microliter.

The trial will measure immune responses to the Tat protein in participants for 144 weeks, or about two and a half years.

For more information on therapeutic vaccine clinical trials, please see the United States Clinical Trial Registry.