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Old vaccine trial draws new scrutiny

By Regina McEnery

On the heels of the premature termination of a Phase IIb HIV vaccine trial in the US known as HVTN 505 (see IAVI Report blog, Large AIDS vaccine trial shudders to a halt, Apr. 26, 2013) comes fresh scrutiny of an earlier Phase IIb study from South Africa that was halted a few months after it started in 2007. The cause: Follow-up studies of participants in that earlier study—HVTN 503, or the “Phambili trial”— 3 ½ years after it was terminated, suggest that volunteers who received the vaccine candidate might have contracted HIV at higher rates than placebo recipients.

The history behind this unhappy discovery is a bit convoluted. Briefly: The Phambili trial was itself halted when another Phase IIb study named Step, which was testing the same vaccine candidate, was found in early analyses of trial data to be ineffective (see IAVI Report article Special Report: 'Stopping a Steam Train', Sep.-Dec. 2007). That analysis also revealed a trend of more HIV infections among certain sub-groups of Step volunteers who received the vaccine candidate.

All three of the trials used the same viral vector—a weakened form of a common respiratory virus known as adenovirus serotype 5 (Ad5)—to deliver genes encoding HIV antigens to vaccine recipients. This, of course, means that the US National Institute of Allergy and Infectious Diseases (NIAID) must now take a close look at the use of all adenovirus vectors in AIDS vaccine studies, even though most are biologically distinct entities.

HVTN 503 was designed to assess an investigational vaccine developed by Merck & Co. for its ability to prevent HIV infection in heterosexual men and women at high risk of infection, or to reduce viral load in those who later became infected. After immunizations were terminated, the 801 participants who had already enrolled in the trial were immediately told whether or not they had received the vaccine candidate, and were asked to undergo HIV testing and counseling every three months for the next 3 ½ years.
 
An analysis of the full 3 ½ year follow-up period reveals that of the 100 monitored enrollees who contracted HIV, 63 came from the vaccine arm. Most of them were men, and the disparity between vaccine and placebo groups was more pronounced 30 months after the initial vaccination. Still, the investigators have been unable to draw any firm conclusions about the findings, largely because the HIV infection status of 189 participants (88 participants in the vaccine group and 101 participants in the placebo group) is not known. NIAID says study investigators will attempt to call other former volunteers to clinical sites for testing.