Officials from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, the NIAID-funded HIV Vaccine Trials Network (HVTN), and study investigators have recently informed the appropriate regulatory authorities in South Africa and the United States of findings from their follow-up analysis of the HVTN 503 “Phambili” HIV vaccine clinical trial in South Africa. This trial was terminated in September 2007 as a precaution after a different trial (the “Step” Study) involving the same candidate vaccine was stopped because of a higher risk of HIV acquisition among participants who received the study vaccine.
The HVTN 503 trial began in February 2007. The study was designed to assess an investigational vaccine developed by Merck & Co., Inc. for its ability to prevent HIV infection in heterosexual men and women at high risk for infection or to reduce virus levels in the blood (viral load) in those who later became infected. The investigational vaccine was a mixture of three weakened adenoviruses acting as vectors, or carriers, for transporting into the body and presenting to the immune system genetic material for three HIV proteins: gag, pol and nef. The weakened adenovirus type 5 (Ad 5) used in the vaccine is a common cold virus that was modified so as not cause a cold or other upper respiratory illness.
At the time vaccinations in the HVTN 503 study were stopped, the study had enrolled 801 participants out of a planned 3,000 participants at five sites in South Africa. Of the 801 study participants, 400 participants received the investigational vaccine. Of those, 112 participants completed one vaccination, 259 participants received two vaccinations; and only 29 participants received all three of the planned vaccinations.
When the vaccinations in the HVTN 503 study were terminated, the participants were immediately told whether or not they had received the investigational vaccine. The participants were also instructed to come to their respective clinic site every three months for HIV testing and continued counseling on how to reduce their risk of HIV infection. This follow up was to occur for 3.5 years.
An initial analysis of follow up data from the HVTN 503 study participants found no significant differences in HIV infection rates between participants who received the investigational vaccine and those who received the placebo. However, in the current analysis of the full 3.5 year follow-up period, the researchers found that 100 study participants became HIV-infected: 63 participants who received the investigational vaccine and 37 participants who received a placebo injection. The increased number of HIV infections among the vaccinated recipients was greatest among men and more pronounced roughly 30 months after initial vaccination. Based on these findings, the study investigators will attempt to recall the former trial participants to the clinical sites for further testing.
In this regard, the HVTN 503 investigators, led by protocol chair Glenda Gray, MBBCH, FCPaeds (SA) of the Perinatal HIV Research Unit, University of the Witwatersrand, based at the Chris Hani Baragwanath Hospital in Soweto, are implementing a follow-up study to invite HVTN 503 participants to be seen by clinic staff to undergo HIV testing and counseling on how to reduce their risk of becoming infected with HIV. The investigators will note HIV infection status and behaviors that may have led to infection and assess perceptions about clinical trial participation and follow-up.
The investigators are unable to draw any firm conclusions about the findings, largely because the HIV infection status of 189 participants (88 participants in the vaccine group; 101 participants in the placebo group) is not known. These volunteers discontinued study participation before completing their final visit. Nonetheless, the differences observed in infection rates between the vaccinated and unvaccinated participants caused sufficient concern to warrant continued follow-up and counseling.
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