The aftermath of the Merck's HIV vaccine trial

The release of the results from the phase III efficacy trial sponsored by Merck, HIV Vaccine Trials Network (HVTN) and the NIAID-NIH has shattered the community of scientists engaged in the field of HIV vaccine. The STEP vaccine trial (also referred to as HVTN 502 or Merck V520-023) relied on recombinant adenovirus serotype 5 (rAD5) as a vaccine vector to induce a strong anti-HIV T-cell immunity. The trial included three rAD5 vectors expressing gag, pol or nef coding sequences and was expected to either prevent vaccinees from HIV infection, or to reduce significantly the plasma viral loads at post-infection set point. The STEP study enrolled 3,000 volunteers at sites in Australia, Brazil, Canada, the Dominican Republic, Haiti, Jamaica, Peru, Puerto Rico and the United States. The first set of results, released in September 2007, showed no protection from infection in rAD5-gag, rAD5pol and rAD5nef vaccinated individuals; surprisingly, the vaccinated cohort showed an increased number of new infections compared with the control group [1]. In fact, an independent Data and Safety Monitoring Board (DSMB) found 24 cases of HIV infection among the 741 volunteers who received at least one dose of the investigational vaccine compared with 21 cases of HIV infection among the 762 volunteers who were vaccinated with placebo. In volunteers who received at least two vaccinations, the DSMB found 19 cases of HIV infection among the 672 volunteers who received the investigational vaccine and 11 instances of HIV infection among the 691 subjects who received the placebo. Surprisingly, the STEP results underscored that people who got the vaccine were more likely to get infected with HIV. Moreover, the increased susceptibility to HIV was preeminent in subjects with pre-existing immunity (antibodies) to adenovirus type 5 (Ad5) (Table 1). As a consequence, enrollments and vaccinations were discontinued. It is noteworthy that the STEP trial was stopped before completing the immunizations in