LACK OF ISOLATE-SPECIFIC NEUTRALIZING ACTIVITY IS CORRELATED WITH AN INCREASED VIRAL BURDEN IN RAPIDLY PROGRESSING HIV-1-INFECTED PATIENTS

Objective: To delineate the interaction between in vivo HIV replicatio n and host antiviral immunity during disease progression in order to e lucidate the pathogenesis of AIDS. Design: In a cohort of HIV-seroposi tive patients, the serum concentration of viral particles, the blood c oncentration of mononuclear cells harbouring infectious virus and the serum titre of isolate-specific neutralizing antibodies were correlate d with the rates of CD4+ T-cell depletion and disease progression. Met hods: Using a quantitative reverse-transcriptase linked polymerase cha in reaction assay, the concentration of viral particles was measured i n blood samples from 103 initially symptom-free subjects who were foll owed up for greater than or equal to 24 months. The concentration of i nfectious virus and the neutralizing antibodies to autologous HIV isol ates were assessed in 37 out of the 103 subjects. The rate of decrease in CD4 cells over the 24 months was calculated for each subject. Resu lts: Rapidly progressing patients (rate of decrease in CD4 cells great er than or equal to 60%) had a high concentration of viral particles a nd a high concentration of infectious virus associated with an undetec table serum titre of isolate-specific neutralizing antibodies. Stable patients (rate of decrease in CD4 cells <30%) had a low concentration of infectious virus and either a low concentration of viral particles with the absence of isolate-specific neutralizing antibodies or a high concentration of viral particles with the presence of isolate-specifi c neutralizing antibodies. Slowly progressing patients (rate of decrea se in CD4 cells greater than or equal to 30 and <60%) showed an interm ediate profile. Conclusions: Progression to AIDS is associated with a shift in the balance between viral replication and host immunity that increases the concentration of infected cells and destroys the CD4+ T- lymphocyte population.