Long-term follow-up of study participants from prophylactic HIV vaccine clinical trials in Africa

Abstract

Long-term safety is critical for the development and later use of a vaccine to prevent HIV/AIDS. Likewise, the persistence of vaccine-induced antibodies and their impact on HIV testing must be established. IAVI has sponsored several Phase I and IIA HIV vaccine trials enrolling healthy, HIV-seronegative African volunteers. Plasmid DNA and viral vector based vaccines were tested. No vaccine-related serious adverse events were reported. After completion of vaccine trials conducted between 2001-2007, both vaccine and placebo recipients were offered enrolment into an observational long-term follow-up study (LTFU) to monitor potential late health effects and persistence of immune responses. At scheduled 6-monthly clinic visits, a health questionnaire was administered; clinical events were recorded and graded for severity. Blood was drawn for HIV testing and cellular immune assays. 287 volunteers were enrolled; total follow-up after last vaccination was 1463 person years (median: 5.2 years). Ninety-three (93)% of volunteers reported good health at their last LTFU visit. Infectious diseases and injuries accounted for almost 50% of the 175 reported clinical events, of which over 95% were mild or moderate in severity. There were 30 six pregnancies, six incident HIV infections and 14 volunteers reported cases of social harm. Persistence of immune responses was rare. No safety signal was identified. No potentially vaccine-related medical condition, no immune mediated disease, or malignancy was reported. HIV vaccines studied in these trials had a low potential of induction of persisting HIV antibodies.

Keywords: Africa; HIV vaccine trials; healthy adult volunteers; long term follow-up; safety.

Figure 1. CONSORT diagram showing the flow of participants from HIV vaccine trial participation through LTFU.

Figure 2. ELISPOT Responses of 29 V001 Individuals with 4 or more LTFU visits. (A) Overall median SFC/m PBMC with interquartile ranges (positive responses only) (B) Data from 6 individuals illustrative of responses over time. Each set of symbols (e.g., circles or triangles) represents an individual, the scatterplots show the responses over 2–6 time points spanning the first visit at 1 y post last vaccine to 5 y post last vaccine. The geometric mean is shown by the bar (-).