Objectives: The primary objective of this study was to expand the safety and immunogenicity database of recombinant gp160 as a therapeutic vaccine in the treatment of HIV-infection. Preliminary efficacy data was also sought.
Design: This trial was a randomized, double-blind, placebo-controlled study. Two-hundred and eight volunteers, 96 therapy-naive with CD4 cell count >500×106/l (group A) and 112 with CD4 cell count of 200-500¥106/l (group B, 51 out of 112 on treatment with one or two nucleoside analogues), received monthly injections of rgp160 IIIB vaccine or placebo for the first 6 months of the study; booster immunizations with rgp160 MN or placebo were given at times 15, 18, and 21 months.
Methods: Safety and immunogenicity data were obtained and measurements of CD4 cell count, plasma viral RNA, and proviral DNA were performed. Clinical outcome was recorded for the 24 months of study.
Results: The vaccine was safe and well tolerated. Despite the induction of new rgp160-specific lymphoproliferative responses and the presence of positive delayed type hypersensitivity skin tests to rgp160 at the end of the 24 month study, no effect on the natural history of HIV infection was detected. Within 24 months, AIDS-defining illnesses had occurred in 19 of the vaccinated volunteers and in 18 of the placebo recipients. Persons with higher plasma viral RNA levels and higher proviral DNA had a more rapid decline in CD4 cell count when compared to persons with lower values. Vaccine did not alter viral RNA or proviral DNA levels.
Conclusion: There was no clinical benefit to therapeutic immunizations with rgp160, despite the induction of new lymphoproliferative responses.
From the Medizinische Poliklinik, University of Munich, Germany, aIMMUNO AG, Vienna, Austria, bSaint Louis University, St. Louis, Missouri, USA, the cInstitute of Immunology, Vienna, Austria, dUniversity of Zürich, Zürich, Switzerland, eHarvard University, Boston, USA, the fRoyal Free Hospital, School of Medicine, London, UK and the gInstitute of Molecular Virology, GSF, Munich, Germany. †See Appendix.
Sponsorship: Supported by IMMUNO AG, Vienna, Austria.
Requests for reprints to: F.-D. Goebel, Department of Infectious Diseases, Medizinische Poliklinik, Klinikum Innenstadt, University of Munich, Pettenkoferstr. 8a, 80336 Munich, Germany.
Received: 16 July 1998; revised: 5 May 1999; accepted: 11 May 1999.