Immunotherapy for Infectious Diseases

210 Jacobson
HUMAN STUDIES
Polyclonal Antibody Preparations
A number of preliminary clinical studies have been performed to evaluate HIVspecific
passive immunization as treatment for HIV infection. In 1988, Jackson et al.
(124) reported infusing plasma containing high levels of anti-p24 antibodies into six
patients with advanced HIV infection. The infusions resulted in losses of plasma p24
antigen, fewer patients with positive plasma and lymphocyte HIV cultures, a reduction
in opportunistic infections, better symptom and Karnofsky performance scores, and
gains in weight (124).
Karpas et al. (125) gave monthly infusions of anti-HIV hyperimmune plasma to 10
patients with advanced HIV infection. Plasma p24 antigen and HIV DNA were reduced
(125). However, the polymerase chain reaction (PCR) assay used to measure plasma
HIV DNA was invalidated in a later study (126).
Jacobson et al. (127), in a double-blind, randomized, controlled trial of hyperimmune
plasma pools prepared in the same manner as Karpas et al. (126), followed in 63 patients
with advanced HIV infection. Plasma donors were asymptomatic HIV-infected individuals
who had CD4 cell counts � 400/mm 3 and were p24 antigen-negative. Plasma recipients
received either 250 mL of anti-HIV hyperimmune plasma or control non-HIV-infected
plasma every 4 weeks. No effects were seen on CD4 lymphocyte counts or plasma and
cell HIV culture titers. However, statistically nonsignificant trends toward delayed time to
opportunistic infection and time to death were noted. No effects on weight, Karnofsky performance
score, or serum �2-microglobulin levels were seen (127).
Vittecoq et al. (128) infused single-donor plasma containing high titers of p24 antibody
at 2-week intervals into nine subjects with advanced HIV infection (CD4 cell
counts �100/mm 3 ). This was a nonblinded, randomized controlled study. HIV p24
antigen became nondetectable in all patients receiving hyperimmune plasma. Fewer
opportunistic infections were observed in the treated patients. No effects on CD4 lymphocyte
count, weight, or Karnofsky performance score were seen (128).
Levy et al. (129) performed a double-blind, randomized, controlled study of anti-
HIV hyperimmune plasma in 220 patients with advanced HIV disease. These patients
received either 250 or 500 mL of the hyperimmune plasma or albumin once a month
for 1 year. The hyperimmune plasma was pooled from HIV-infected donors with high
titers of anti-p24 antibodies. No benefit of treatment was seen in the study population
as a whole. However, subset analysis of patients with CD4 lymphocyte counts between
50 and 200/mm 3 who received the 500-mL/month dose of hyperimmune plasma showed
them to have statistically significant improvements in CD4 cell counts and trends
toward longer survival and lower serum HIV p24 antigen levels. No effects on the
occurrence of opportunistic infections or serum �2-microglobulin were seen (129).
These studies were performed prior to the availability of the current techniques to
measure plasma HIV load by RNA levels. Subsequently, Vittecoq et al. (130) performed
a double-blind, controlled trial of single-donor hyperimmune plasma versus
HIV-negative plasma in 82 patients with CD4 lymphocyte counts �200 cells/mm 3 .
Plasma was given in doses of 300 mL every 2 weeks for 1 year. Treatment resulted in
delayed occurrence of opportunistic infection. A nonsignificant trend toward improved
survival was seen. There was no effect of treatment on CD4 lymphocyte counts (130).