The Potential Use of HIV Vaccines for the Treatment of HIV Infection: Scientific Summary of the State-of-the-Art

What have we Learned to Date from Clinical Trials of Prophylactic HIV Vaccines
Candidates?
Clinical trials of prophylactic HIV vaccines undertaken to date have been
Phase I trials intended to determine whether or not vaccine candidates are
safe, and to characterize the type, magnitude, and duration of the immune
responses that the vaccine elicits in individuals at low risk for exposure to
HIV.
The NIH has established an infrastructure to evaluate candidate vaccines in
Phase I and II trials. This includes NIAID's intramural Laboratory of
Immunoregulation and NIAID's extramural AIDS Vaccine Evaluation Group (AVEG).
AVEG consists of a consortium of 5 academic groups that recruit, immunize, and
perform some immunologic evaluations. Additional standardized immune assays
are performed by a Central Immunology Laboratory. The AVEG Data Coordination
and Analysis Center collects and analyzes data from the sites and the central
laboratory.
Sixteen vaccine candidates have been or are being evaluated in clinical trials
in HIV seronegative individuals in the U.S., Europe and Africa. To date, the
NIH is evaluating seven of these products in a total of nine Phase I protocols
in seronegative individuals. Products evaluated by the NIH include the gpl60
products from MicroGeneSys and ImmunoAG, two envelope products from Biocine
(env 2-3 and gpl20), two envelope products from Genentech (gpl20-LAI and
gpl20-MN) and a recombinant vaccinia expressing gpl60 from Bristol-Myers
Squibb (HIVAC-le) (TABLE 3). A recombinant canary pox virus expressing gpl60
from Pasteur-Merieux-Serums et Vaccins is about to enter clinical trial in the
AVEG pending FDA approval. Five additional Phase I trials including 3
additional new candidate vaccines not previously evaluated in humans and a
comparative adjuvant study are scheduled to begin in 1993 (TABLE 4), pending
FDA approval.
The NIAID will also soon begin the first Phase II trial to evaluate safety and
immunogenicity of one or two candidate vaccines in larger numbers of persons
including some at higher risk for exposure to HIV. The demographic
distribution of seronegative volunteers participating in trials of candidate
vaccines is shown in the accompanying table (TABLE 5).
To date, all HIV vaccine candidates that have been evaluated by the NIAID in
Phase I human clinical trials in seronegative individuals have been safe and
well tolerated (3-5, 10-15, 17-21, 47, 55). Observed side-effects include
those typical of vaccines such as local pain and tenderness, low-grade fever
and minor systemic symptoms, some of which also occur in placebo recipients.
No major side effects such as renal, hepatic or neurologic toxicity have been
reported to date. Use of the adjuvant MTP-PE in the vaccine formulation has
resulted in moderate side effects in some volunteers; these included malaise
and fever that resulted in absences from work or school (19). Finally, the
concern that gpl20 or gpl60 might result in a decline in CD4 cell count as a
result of binding to CD4+ cells has not been validated; CD4 cell count and
blastogenic responses to mitogens and to recall antigens such as tetanus
toxoid in vaccine recipients have not declined to date (5, 15, 19, 21, 22, 25 -