Immunotherapy for Infectious Diseases

Passive Immunotherapy for HIV Infection 211
No difference between treatment groups in plasma HIV RNA levels was seen, but more
patients receiving hyperimmune plasma than those receiving HIV-negative plasma had
negative plasma HIV cultures (but not cellular cultures) during the study period (131).
In a different approach, Osther et al. (132) infused a porcine hyperimmune globulin,
created by immunizing pigs with an HIV lysate, once daily for 5 days into 14
patients with HIV infection. These infusions resulted in loss of p24 antigenemia,
enhancement of CD4 cell counts, and improved symptoms (132).
HIVIG was studied in the Pediatric AIDS Clinical Trials Group (PACTG) Protocol
185 for its potential effect on reducing perinatal transmission of HIV. An unexpectedly
low overall transmission rate resulting from zidovudine (AZT) treatment caused the
trial to be stopped early without determining the effectiveness of HIVIG. However,
there were statistically nonsignificant trends toward reduced transmission with HIVIG
treatment in women with CD4 lymphocyte counts �200/mm 3 and in women who had
started receiving zidovudine before they became pregnant. Presumably, these were
women with more advanced disease and greater risks of transmitting infection to their
newborns. In addition, none of the 9 infected neonates in the HIVIG arm of the study
had positive HIV cultures at birth compared with 5 (38%) of 13 infected neonates in
the IVIG arm, a statistically significant difference (133). Thus, passive immunization
with HIVIG may have been effective in reducing transmission in the subset of patients
at greatest risk to do so, and this may have affected the degree of viral replication in
those infants who did become infected. However, an effect on plasma HIV RNA levels
was not seen in PACTG Protocol 273 when 30 HIV-infected children aged 2–11
years on stable anti-retroviral therapy were given 6 monthly infusions of 200, 400, or
800 mg/kg of the same HIVIG preparation (134).
Monoclonal Antibodies
Hinkula et al. (135) studied two different murine monoclonal antibodies, F58 and
P4/D10, targeting the V3 loop of HIV-1IIIB, a TCLA strain. One of the antibodies was
given twice a month for 3 months to 11 patients with AIDS. The antibody administered
neutralized the primary virus isolate of 9 of the 11 recipient patients. Plasma HIV RNA
decreased in four patients, remained stable in another four, and increased in three
patients. There were no changes in CD4 cell counts, but mitogen- and non-HIV
antigen-induced lymphoproliferative responses improved in 9 of 11 patients (135).
Gunthard et al. (136) studied a chimeric mouse-human monoclonal antibody (CGP-
47-439) against the V3 loop of HIV-1IIIB, MN laboratory-adapted strains. This chimeric
antibody was derived from the murine BAT123 monoclonal antibody. Various doses
were given to 12 patients at 3-week intervals for 24 weeks. Plasma HIV RNA levels
decreased in two patients and increased in one (136).
In sum, although a number of these human studies suggested a clinical benefit from
the administration of various passive immunization products, no clear antiviral effect
has been demonstrated to date.
CONCLUSIONS
There is now a body of evidence showing that antibodies have the ability to prevent
and control HIV infection. Antibodies with neutralizing activity against strains of HIV
in vitro are able to protect animals against infection with those strains. These include