PROCAARE: BASIC SCIENCE--Immunology

[Albert Shaw <ashaw@usa.healthnet.org>]

KEYWORDS: IMMUNOLOGY/IMMUNIZATION/VIRAL BURDEN/CELLULAR ACTIVATION
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Reference: Stanley, S.K., Ostrowski, M.A., Justement, J.S., Gantt, K., 
Hedayati, S., Mannix, M., Roche, K., Schwartzentruber, D.J., Fox, C.H., 
Fauci, A.S. (1996).  Effect of immunization with a common recall antigen 
on viral expression in patients infected with human immunodeficiency 
virus type I.  New Engl. J. Med. 334: 1222-30.

This study enrolled 13 HIV-1-infected patients (all homosexual men) and 
10 HIV-negative controls; all participants were given a 0.5 ml 
intramuscular dose of tetanus toxoid.  Plasma samples assayed pre- and 
post-immunization revealed a transient increase in viremia (assayed by 
HIV-1 RNA) in all HIV-1-infected subjects; these increases ranged from 2 
to 36-fold, peaked an average of 13 days post-immunization (range 3-28 
days), and returned to baseline within 6 weeks.  10 of the 13 
HIV-positive patients demonstrated higher (by 2-4 fold)  numbers of 
infected peripheral blood mononuclear cells (PBMC).  The CD4 count 
decreased in 10 of 13 in the HIV-positive group, but the overall median 
decrease (from 362 to 274/mm3) did not reach statistical significance 
(p=0.066).

In 9 of 13 HIV-infected subjects, HIV-1 could be more easily isolated 
with PBMC's following immunization.  Interestingly, PBMC's from normal 
subjects were more readily infected with HIV-1 following tetanus toxoid 
treatment.

This report indicates that the cellular activation associated with 
immunization can result in a transient increase in HIV-1 expression.  The 
authors do not advocate deferring necessary immunizations in HIV-positive 
patients, given the transient nature of the observed increased viremia 
and the protective benefits of immunization.  However, these results may 
be relevant to patients with chronic infections which cause a consistent 
state of immune system activation; the authors use as an example 
parasitic infections, and suggest that the increased rate of HIV disease 
progression observed in sub-Saharan Africa may be in part due to such 
chronic cellular activation.