Pharmexa-Epimmune, a US subsidiary of a Danish vaccine and immunotherapy company, recently initiated a Phase I AIDS vaccine trial to evaluate the safety and immunogenicity of two candidate vaccines that will be tested either alone or in combination. This trial will enroll 124 volunteers at 3 sites in the US and in Lima and Iquitos, Peru, in partnership with the HIV Vaccine Trials Network (HVTN).

The first candidate, known as EP HIV-1090, is a DNA plasmid vaccine that has already undergone testing in human volunteers while the second, EP-1043, is a protein vaccine designed to induce cellular immunity. Neither candidate can cause HIV infection. In the first part of this trial volunteers will be randomly selected to receive either a low or high dose of EP-1043 to determine which is optimal. In the second part of the trial researchers will be comparing the safety and immune responses generated by EP-1043 and EP HIV-1090 alone or in combination. Volunteers will be randomized to receive four inoculations of either vaccine candidate or four injections of both.

This trial is sponsored by the US National Institutes of Allergy and Infectious Diseases within the National Institutes of Health and the vaccines are being manufactured by Pharmexa-Epimmune.

India started the country's second Phase I AIDS vaccine trial recently in Chennai to determine the safety and immunogenicity of a modified vaccinia Ankara (MVA) vaccine candidate at varying doses. This trial will enroll and follow 32 volunteers at the Tuberculosis Research Centre over 2 years.

The vaccine candidate, TBC-M4, uses a weakened and non-infectious MVA virus as a vector to deliver HIV fragments to the immune system, but importantly the candidate can not cause HIV infection because only part of the virus is used. The fragments included in the candidate are from clade C HIV, which is the predominant virus circulating in India and China, as well as parts of Africa. Researchers and an independent advisory board will evaluate the safety of the candidate at the low dose before administering a higher dose to volunteers in this trial.

IAVI is sponsoring the trial in partnership with the Indian Council of Medical Research and the National AIDS Control Organization of India. Therion Biologics, a US-based biotechnology company, is manufacturing the vaccine.

India is also conducting another Phase I AIDS vaccine trial with a different vaccine candidate that began last year and is ongoing at the National AIDS Research Institute in Pune.

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All articles written by Kristen Jill Kresge

What are the major considerations influencing the decision to volunteer for an AIDS vaccine trial?

Making the decision to participate in an AIDS vaccine clinical trial is a complex and personal process and it is important that all potential volunteers fully understand what is involved in the trial when making this choice. Researchers and staff conducting AIDS vaccine trials take several measures to ensure that, to the best of their ability, any possible benefits and risks of trial participation are identified. These are then reviewed before the trial begins by local and independent groups known as ethical review committees (ERC) or institutional review boards (IRB) and sponsors to ensure the list is complete. The ERC is committed to ensuring that the trials are run to the highest safety and ethical standards. All of the possible benefits and risks are also explained carefully to each interested volunteer during the informed consent process (see June 2005 Primer on Understanding Informed Consent).

Benefits

There are several ways that clinical research, including AIDS vaccine trials, can benefit the countries and communities in which the trials take place even if the vaccine candidate being tested is eventually found to be not effective. Before AIDS vaccine trials are conducted, educational campaigns take place to raise awareness within the community about HIV transmission and prevention and these can benefit all community members, not just those who choose to volunteer for the trial. Many of these outreach programs also promote voluntary counseling and testing (VCT) for community members to find out if they are HIV infected, which can influence future decisions about their health and help reduce the stigma associated with HIV testing.

There are also several possible benefits for those who decide to participate in an AIDS vaccine clinical trial. They include the VCT services and risk-reduction counseling that the volunteers will receive regularly throughout the course of the trial (see August 2005 Primer on Understanding Risk-Reduction Counseling). Volunteers will also have continuous access to the best available prevention measures in their community, including male and female condoms. Participants in AIDS vaccine trials also benefit from the rewarding feeling of being involved in medical research that may benefit others. Altruism, or concern for the welfare of others, is one of the most common reasons trial volunteers give for their participation.

Other possible benefits include the basic medical care that volunteers receive during the trial. People interested in volunteering for AIDS vaccine trials who are found to have malaria or tuberculosis can receive referrals to treatment programs in their community, therefore improving their overall health. This is also true for people who are found to be HIV infected or who become HIV infected during the course of the trial through exposure in their community. These individuals can be referred to treatment programs, as well as to support groups.

Volunteers in AIDS vaccine trials might also receive reimbursement for transportation to and from the trial site or for food if they are expected to be at the site during a mealtime. A reasonable amount is determined, with input from the community advisory board, before the trial begins and is reviewed and approved by the ERC.

Researchers and the ethics committees take these considerations seriously because they don't want the compensation or the health care provided at the trial sites to be the reason that people join the study. All trial organizers and approval bodies work carefully to avoid undue inducement. To prevent this, some trial sites may strive to provide a level of care that is consistent with what is available in the broader community. Other sites try to extend some basic healthcare services as much as possible to the wider community, which can be difficult at urban sites.

Volunteers should not feel pressured by the trial staff into enrolling in a trial but should make a decision only after weighing all of the potential benefits and risks. Ethicists are also studying how to ensure that adolescents fully understand the risks and benefits of participation in medical research before agreeing to enroll. This may be an important issue in the future as researchers consider the possibility of testing AIDS vaccine candidates in this age group.

Risks

It is equally important that all volunteers understand the potential risks of participating in AIDS vaccine clinical trials. All vaccine candidates are tested extensively before they enter human clinical trials, but there is still the possibility that there will be side effects or adverse reactions caused by the vaccine candidate. Often these are mild and can include headaches, fever, and inflammation at the injection site, but these effects should be explained to all volunteers clearly during the informed consent process. However, researchers can't predict each individual's response to the vaccine.

It is also critical for volunteers to understand that there is a possibility that the vaccine candidate will not be effective or that they will be randomly selected at the start of the trial to receive an inactive substance known as a placebo. Either way, the volunteers won't be protected against HIV infection by participating in the trial, emphasizing the need to practice risk-reduction behaviors.

Other potential risks include the possibility of receiving a false-positive HIV test result in the future (see November 2005 Primer on Understanding HIV Testing), being unable to donate blood after participation in the trial, and social risks such as facing possible stigma or discrimination.

Despite these inherent risks, researchers and trial staff are dedicated to making sure that AIDS vaccine trials are run safely and ethically and that these trials contribute to the overall health and welfare of the communities that participate in AIDS vaccine research, especially in developing countries.