HIV antibody testing for vaccine trials: Thailand highlights problems

In the course of a study of HIV and other health risks among male prisoners in Thailand, two men were identified who tested weakly positive or gave indeterminate results on initial screening tests. However, neither man was in fact HIV positive, once PCR tests for viral nucleic acid were used. Both turned out on further investigation to have been volunteers in the ongoing gp120 HIV vaccine trial sponsored by VaxGen, which has recruited more than 2,500 Thai injecting drug users - half of whom have received the vaccine - since 1999 (Suthon).

While the researchers were able, with excellent laboratory facilities, to establish that these two men were in fact not HIV positive, their vaccination status hadn't been revealed in the pre-test counselling or, in one case, through four research interviews. Once their vaccination status was known, it became clear that the Western Blot test result confirmed this - showing antibodies to gp120 but to no other HIV antigens. Arguably, Western Blot should have been sufficient in this case to establish their status, without PCR.

The report highlights the need for voluntary counselling and testing procedures and technologies in routine use to be adapted as HIV vaccines come into use. People need to be asked if they have received a vaccine, and may need special testing depending on which vaccine they have received and when.

The nature and extent of this problem will vary from vaccine to vaccine and becomes more serious, when vaccines include a wider range of HIV antigens and induce stronger immune responses.

A joint Thai/American study, presented at the XIV International AIDS Conference in Barcelona, carried out extensive tests on sera from low-risk Thai and American volunteers in canarypox/gp120 prime-boost trials. These were held in preparation for large-scale trials due in Thailand within the next year. The researchers found that at the time of peak immune response to this vaccine combination, nucleic acid testing (PCR or other viral load tests) was essential to distinguish between vaccine responses and true infection (Malia).

This could add greatly to the cost of large-scale trials, and in due course to the provision of VCT services, depending on how fast the peak immune response fades after vaccination and the period for which it is considered reasonable to wait before testing individuals for HIV. As it becomes clearer, which vaccines will go forwards into large-scale tests and may subsequently enter wider use among people at high risk, so attention must be paid to developing inexpensive and practical tests that can distinguish between vaccination and HIV infection.

VaxGen's Thai trial to go the full distance

The independent Data and Safety Monitoring Board that oversees VaxGen's clinical trials has completed their seventh and final safety and conduct review of the company's Phase III trial in Thailand. As before, it has concluded that the study was being conducted appropriately and that VaxGen's AIDSVAX appears safe, the company has announced.

The Board has said nothing about the efficacy of the vaccine: however, if there had been results that clearly proved its efficacy or lack of it, the trial would have been stopped.

Retention of volunteers in the Thai study remained above expectations with a claimed 96.7% of the volunteers still being followed as of 15 September 2002. It was reported earlier this year that this level of retention could not have been achieved, but for the commitment of trial staff to see some of the volunteers in prison - although all were recruited through clinics run by the Bangkok Metropolitan Authority while outside the prison system (Pitisuttithum).