Seattle Treatment Education Project: STEP Perspective - Volume 4, Number 3 - October 1992
Mari Kitahata, M.D.

Dr. Redfield presented updated results from the Phase I trial of gp160 that appeared in the New England Journal of Medicine last year (1991.324:1677-1684. TuB 0563). Originally, 30 HIV-infected volunteers were immunized with rgp160 in either three or six scheduled doses. Nineteen or 30 demonstrated new antibody responses to selected envelope epitopes and many new T-cell responses not induced as a consequence of natural infection. There was, however, no placebo controlled arm to assess the immune response in native infection. The 11 non-responders had lower CD4 counts initially, and had received only three doses of vaccine. Twenty-eight of 30 agreed to re-enroll in a continuation trial and received a rollover infection series (18 of 19 vaccine responders and 10 of 11 non-responders). Nine of 10 non- responders developed new humoral and cellular immune responses to booster infections of gp160. All initial responders showed continued increases in immune response, demonstrating no tolerance to repeated immunizations. Toxicity remained limited to local reactions post-immunization. A reduced viral load was detected in seven of 11 patients evaluated.

Redfield also presented the Walter Reed Army Medical Center study of rgp120 in 42 HIV-infected patients with CD4 counts greater than 500 (TuB0564). This study was placebo controlled and double blinded. Significant increases in envelope antibody and lymphocyte proliferation were observed. A greater response was seen in patients immunized with higher doses. The McGill AIDS Center study (TuB0560) enrolled 21 patients with CD4 counts over 500 to receive five immunizations of rgp160. Therapy was well tolerated, and resulted in new and augmented antibody production, greater lymphocyte proliferative response, and increased CD4 counts (mean increases = 117) as well as percents (mean increase = 2). Repeated analysis showed a statistically significant rate of increase in these outcomes after a year of follow-up.

The NYU/Stanford randomized, controlled trial (TuB0561) of rgp160 in 52 patients with CD4 counts over 500 also demonstrated the safety of the vaccine and its ability to induce a variety of new immune responses not detectable prior to immunization. However, there are no data, to demonstrate that this heightened immune response improves the clinical course and prevents progression of HIV disease.

A Phase I/II study of rgp160 and p24 vaccines in 60 HIV-infected patients at all stages of disease was presented from the Southern New England Community Consortium in Greenwich, Connecticut (TuB0562). All 16 individuals with initial CD4 counts between 200 and 500 demonstrated a positive immune response, and improvements in mean CD4 counts. CD4 counts increased from a baseline of 348 to 425, 456, 419, and 390 at 4, 5, 6, and 12 months respectively. All remained clinically well at 18 months without progression to ARC or AIDS. No statistically significant differences were seen in individuals with CD4 counts below 200.

The positive humoral and cellular response to recombinant envelope protein vaccines observed in all five trials is very encouraging. Larger placebo controlled studies with clearly defined endpoints are needed to evaluate the clinical benefit of therapeutic vaccines.

Copyright (c) 1992 - STEP. Noncommercial reproduction encouraged.
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