Dr Glenda Gray, director of the Wits Perinatal HIV Research Unit, today presented an “interim efficacy” analysis of data collected in the South African Phambili HIV Vaccine study.
This human clinical trial was halted in September 2007 due to futility (not showing efficacy) found in its companion study known as the STEP study. Both these trials were set up to test the same vaccine, the Merck Adenovirus 5, in uninfected adults.
Concern was raised at the time that uncircumcised men, who had pre-existing immunity to the Adenovirus 5, could be at slightly raised risk. But subsequent analysis of the STEP and Phambili data and follow up presented today showed that this was not in fact associated with increased risk of being infected. In the Phambili trial less than 20% of the participants had no pre-existing immunity to Ad5.
The trial was run in five provinces in South Africa with sites in Gauteng, North West, KwaZulu-Natal and the Western Cape and patients were followed up after September 2007 (data was frozen in August 2009).
Among the major findings that Gray presented were:
*This vaccine did not protect against HIV and there were no difference in new infections between the vaccine and placebo groups by the time of the first vaccination;
*But good cross clade immune reactivity was demonstrated: the vaccine being tested was a sub-type B candidate in an area where sub-type C is most common, but this finding shows at four weeks after two injections most volunteers had developed an immune response to both clades B and C (for clade C the response rate was 77%);
*A reduction in HIV viral load among the women who received the vaccine: 0.57 log reduction in viral load at the set-point (measured at the start of the study);
*early differences in CD4 decline between the vaccine and placebo participants: CD4 counts indicate immune strength so a slower decline is advantageous and over 12 months the vaccine group experienced this benefit but it was not sustained over time;
*Risk reduction behaviour was sustained over time; and
*Good uptake of male circumcision post-enrolment of about 32%: medical male circumcision reduces the risk of a man acquiring HIV by about 60% many studies have proved.
The new HIV infection rate that Gray reported was roughly 4% – about 10 to 20 times higher than the infection rate in the Thailand trial which was conducted among a low-risk population.
The number of vaccinations received did not impact on the probability of acquiring HIV (no statistical difference was found). During the trial 60 volunteers were infected – 40 of them were women.
Two-thirds of the volunteers got two vaccinations and a quarter got only one shot before the trial was suspended.