Int Conf AIDS. 1992 Jul 19-24;8(3):36 (abstract no. PuA 6153). Unique
OBJECTIVE: Follow-up of individuals initially presenting with
border-line or low-positive screening results and a Western blot result
at least positive according to CDC/WHO interpretation, but
FDA-indeterminate. METHODS: All individuals with such results were
enrolled into a follow-up study and tested by WB (serum dilution 1/25),
serum Ag, virus culture (VC) and PCR, using primers/probes from gag,
env, and LTR. The analytical sensitivity of the PCR procedure was shown
to be 1 copy/microgram DNA. The specificity of a positive PCR reaction
was 99.25% (4 false-positive out of 531 negative control reactions) and
that of a positive PCR result 100% (187 materials tested). WB results
were evaluated according to CDC, CRSS, ARC, and FDA interpretation
rules. RESULTS: On follow-up, in 19 (56%) of 34 cases enrolled in 1991
anti-env antibodies were no longer present. In these, contamination of
the first sample could not be ruled out as a cause for the initial
positivity. Of the remaining 15, only 6 (40%) were shown to be infected
by PCR and, in 5, by full seroconversion; 2 were VC+ and 1
indeterminate, but all were Ag-neg. Of the remaining 9 (60%), 7 were
still WB-pos by at least CDC interpretation, but did not fully
seroconvert. Two more were CDC-indeterminate, but still had anti-env
antibodies. All 9 were negative by Ag, VC and PCR, except 1 case who was
PCR indeterminate in 1 of 2 follow-up samples. Long-term observation of
18 different such individuals detected earlier showed the continued
presence of such antibody patterns in otherwise healthy individuals for
up to 5 years. PCR results were never clear-positive, but showed an
indeterminate result in 4/18 cases. Antibody patterns and concentrations
varied over time, some individuals became again screening-negative.
CONCLUSION: The results show that less than half of the individuals
presenting with serological results suggestive of early HIV infection
rapidly progress to a state where HIV infection can be demonstrated
beyond doubt. At least as many of these individuals remain, sometimes
for years, in a state of diagnostic twilight, where both serological and
PCR results are borderline. Strict adherence to the WB interpretation
rules suggested by CDC or WHO may lead to confirmed false-positive
results. If, on the other hand, these individuals are truly infected,
they represent a stable state of low-level infection that is different
from that of fully seroconverting individuals. The most sensitive
diagnostic tests are not sensitive enough to resolve this problem.
Antibodies/*BLOOD Blotting, Western False Positive Reactions
Follow-Up Studies Gene Products, env/IMMUNOLOGY Genes, env Genes, gag
Human HIV/GENETICS/*ISOLATION & PURIF HIV Antibodies/*BLOOD HIV
Infections/DIAGNOSIS/*IMMUNOLOGY/PHYSIOPATHOLOGY *HIV Seropositivity
Polymerase Chain Reaction Prospective Studies Time Factors ABSTRACT