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AIDS that follows for immunologic parameters in persons <6 years of age).[207,209] A total
lymphocyte count of greater than 1250/µL is nearly as good as a CD4 count of greater than
200/µL at predicting that the stage of clinical AIDS has not been reached.[383] Elevated levels
of soluble CD30 activation molecule from T-lymphocytes is another factor that is associated
with progression to AIDS independent of other factors.[66]
The CD4 lymphocyte count can demonstrate variability, even in the same patient. There
can be diurnal variations of more than 100/µL in the CD4 lymphocyte count in the same day due
to diurnal variations. Additional laboratory testing factors play a role in measurement of CD4
lymphocytes and include variations in total white blood cell count, lymphocyte percentage, and
CD4 percentage. Physiologic factors may include exercise as well as consumption of tobacco,
alcohol, and caffeine.[384,385]
Serum beta -microglobulin (B2-M) is a polypeptide that forms the light chain of class I
2
major histocompatibility complex antigens found on most nucleated cells, can be measured by
immunoassays such as EIA. Rising levels of B2-M, which usually increases above background
in serum within 6 months of seroconversion, can be used as a marker of disease progression in
HIV infection. Increased levels of B2-M in cerebrospinal fluid can be helpful as a marker for
HIV-related neurologic diseases such as HIV dementia. Increased levels of B2-M also predict
progression to AIDS in perinatally acquired cases of HIV infection. Zidovudine therapy appears
to decrease B2-M levels in serum for 2 to 3 months following initiation of therapy, but levels
increase to pretreatment levels by 6 months.[209]
Inflammatory biomarkers that may accompany HIV and response to treatment may
include high sensitivity C-reactive protein (hs-CRP), D-dimer, and interleukin-6 (IL-6). Both hs-
CRP and IL-6 appear to increase with progression of HIV infection. The D-dimer decreases in
response to antiretroviral therapy.[386]
Neopterin is a product of macrophages and B-lymphocytes stimulated with interferon
gamma. It increases in a variety of inflammatory conditions. Neopterin can be measured in
serum, urine, and cerebrospinal fluid by radioimmunoassay and by chromatography. Increasing
serum neopterin levels correlate with progression of HIV infection to AIDS. Within 1 to 2
months following initiation of zidovudine therapy, neopterin levels initially fall, then increase
slightly and remain below pretreatment levels for about a year.[209]
STRATEGIES FOR HIV TESTING.-- The primary approach to detection of HIV
infection remains use of EIA serologic tests for HIV antibody. In developed nations, EIA tests
for HIV antibody must be repeatedly reactive and confirmed by Western blot (WB) confirmatory
testing before reporting as positive. Alternative strategies that employ two or more separate
methodologies can be utilized to provide high sensitivity and specificity, while avoiding the use
of WB that is technically difficult and may yield indeterminate results.[387] False negative
results are extremely uncommon, and with repeat testing after 3 months to avoid the "window"
of possible seronegativity following initial HIV infection, virtually eliminated. Perinatal
infections can be confirmed by p24 antigen assay, HIV IgA assay, HIV-1 RNA assay, and by
HIV viral culture. HIV-1-RNA assay is most often the practical choice. Disease progression
and response to antiretroviral therapies can be monitored with measurement of plasma viremia
by PCR or by following the CD4 lymphocyte count.
The World Health Organization (WHO) has devised a testing approach that does not
require use of the WB test. Strategy I is employed in places where the prevalence of HIV
infection is 10% or greater, relies on a single rapid EIA test and is recommended for blood