Case 9: Testing a New Vaccine

Part I

Viravax, a UK-based company has developed a vaccine against HIV that appears promising. Animal studies were very successful and phase I and phase II trials demonstrated that the vaccine was remarkably safe and that it produced significant antibody levels in essentially all of the volunteers. The company now wishes to begin phase III trials in Ho Chi Minh City, Vietnam where previous surveillance has identified a cohort of intravenous drug users (IDU) with a high rate of conversion to HIV-1. Such a study could be completed in two years. The Vietnamese Government has expressed interest in having the study conducted and begins negotiations with Viravax. The vaccine, which is specifically directed against the strain that predominates in the Vietnamese IDU population, will be provided free by Viravax. Viravax will also cover the cost of conducting the study, which will be carried out by the The Vietnam Vaccine Institute. In addition to the study costs, the company will provide all the laboratory equipment necessary to conduct the studies, ten computers for the Institute, and two vehicles to visit the study sites. The company agrees that if the vaccine proves effective it will be given free of charge to the addict population of the city and at cost to the country for five years.

Discussions are held regarding how to treat persons in either the vaccine or control group that are HIV+. This will be a randomized double blind prospective study with one group receiving the test vaccine and the other group receiving a placebo. All potential participants will be tested for HIV prior to being enrolled in the study and if they are HIV+ they will be referred to one of the municipal hospitals of the Ho Chi Minh City Corporation. It is also agreed by the company and the Institute that anyone who converts to HIV+ during the study will be referred to one of the Municipal Corporation hospitals to be treated by the standard method in the "Guidelines for the Clinical Management of HIV Infection in Children and Adults" published by the Ministry of Public Health. This means that all infections are treated but no patient is given either retroviral drugs, including AZT, or any protease inhibitors. If there is any change in the standard therapy recommended by the government, any previous or future seroconvertor will be switched to this therapy. The Municipal Corporation will provide treatment for the patient's lifetime. Individuals can drop out at any time without fear of prejudice.

Informed consent will be obtained by first briefing possible participants about the study, including the experimental nature of the vaccine, and the treatment policy. Two days following the initial briefing the individuals return to the Institute where they are given a brief oral and written exam to see if they fully understand the study and their rights. Only if they pass the test, are they enrolled. The study is submitted to the Ethical Review Board of the Institute and to a firm that conducts ethical reviews for companies in the private sector who wish to conduct research on human subjects. The protocol is also reviewed informally and commented on by UNAIDS at the request of the Ministry of Public Health Technical Subcommittee on HIV Vaccines. That Subcommittee approves the protocol and forwards it to the Ministry of Public Health Ethical Committee. All review boards approve the study.

After the study has begun, an article appears in a publication of an AIDS activist group condemning the study because it is not providing state-of-the-art care for any individual who seroconverts. They argue that the only reason the study is being conducted in Vietnam is because it is much less expensive to do, as triple therapy is not required (which would be necessary if the study was conducted in the UK). They feel that the study, as presently designed, would never be passed by either a UK government or university ethical review committee. Viravax counters that to use state-of-the-art therapy would in itself be unethical because it would be unsustainable in Vietnam and only one small group would have access to the best. In addition, the physicians in Vietnam would be unfamiliar with the therapy and unaware of all the possible side effects. And lastly, by offering the best care available in the world, the study would be giving an unfair inducement to participate. It would in essence be offering a form of coercion to receive the vaccine.

Questions:

• Is the study unethical because participants are not being offered the best care available in the world if they should become HIV+?
• Would it be unethical to offer state-of-the-art care to seroconvertors even if the care was not available in Vietnam, and was unlikely to be available within the near future except to the very wealthy?
• Is there any compromise position that may be acceptable to both parties?
• If the developer of the vaccine was a Vietnamese company who wished to conduct the study in its own country, would the use of "best available or standard local therapy" for seroconvertors be viewed differently? What are the implications if the standards are different? The same?
• Should the vaccine be tested if it is presently unaffordable to the country for wide distribution?
• Are there any other services that should be provided to the IDU population?

Part II

The study could be conducted in the US using "best therapy" for those who become HIV+. Because of the much lower rate of seroconversion in the IDU population, however, it will take an additional three years to complete the study. It is estimated that from 50,000 t0 100,000 addicts in Vietnam will seroconvert to HIV+ during this three year period. Viravax and other pharmaceutical companies have indicated that there will be other vaccine candidates that will require testing within two years.

Questions:

1. What are the ethics of taking the additional three years to conduct the study of a vaccine that might be effective?
2. Does requiring Vietnam to provide the "best therapy" effectively prevent them from participating in the international testing of HIV vaccines? What are the ethics of keeping Vietnam from testing vaccines?