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
• long term follow-up
• safety
• healthy adult volunteers

10.4161/hv.27559

Disclosure of Potential Conflicts of Interest

IAVI is a non-profit organization; neither IAVI nor IAVI-affiliated co-authors report any competing interests that may interfere with the objective assessment of this manuscript or with the ability to adhere to this journal’s policies on sharing data and materials. The affiliations of L.D. and C.S. do not alter the authors’ ability to adhere to this journal’s policies on sharing data and materials.

Funding

This study was funded by the International AIDS Vaccine Initiative and its donors, including the generous support of the American people through the United States Agency for International Development (USAID; USAID Cooperative Agreement Number GPO-A-00-06-00006-00). The contents of this manuscript are the responsibility of IAVI and do not necessarily reflect the views of USAID or the US government. The following organizations and institutions played a direct role in study design, data collection and analysis, decision to publish, and preparation of this manuscript: International AIDS Vaccine Initiative (IAVI), the Clinical Research Centers (KAVI, UVRI, PSF, Medunsa, DTHC, ZHERP), and the EMMES Corporation. The EMMES Corporation is a Contract Research Organization (CRO), to which IAVI subcontracted data coordination, management, and analysis for this study.

Acknowledgments

IAVI gratefully acknowledges the time and commitment from volunteers, study teams and all staff at the collaborating centers as well as the generous support of its donors to make this work possible. We thank the IAVI Clinical Program Managers Helen Thomson, James Sherwood, and Andrea van Lieven and the study monitors (Apolo Balyegisawa, Kundai Chinyenze, Mabela Matsoso) for their on-site support at the African Clinical Research Centers. We thank all staff from IAVI regulatory affairs, manufacturing, quality control, project teams, medical affairs, and laboratories.

Ethical Statement

The study protocol was approved by all responsible Ethics Committees and the study was conducted according to Declaration of Helsinki, ICH-GCP, and all applicable local regulations. All subjects provided written informed consent.