Page 38 - AIDSBK23C

Page 38

PROGRESSION OF HIV INFECTION

The development of signs and symptoms of AIDS typically parallels laboratory testing
for CD4 lymphocytes. A decrease in the total CD4 lymphocyte count below 500/µL presages
the development of clinical AIDS, and a drop below 200/µL not only defines AIDS, but also
indicates a high probability for the development of AIDS-related opportunistic infections and/or
neoplasms. The risk for death from HIV infection above the 200/µL CD4 level is low.[207,208]
Other laboratory findings which indicate progression to AIDS include HIV p24 antigen
positivity, increased serum beta -microglobulin (B2-M), elevated serum IgA, or increased
2
neopterin levels in serum, cerebrospinal fluid, or urine. The p24 antigen is a highly specific
predictor of progression, but only about 60% of HIV-infected persons develop p24 antigenemia
prior to onset of clinical AIDS. B2-M is a polypeptide that forms the light chain of the class I
major histocompatibility complex found on the surface membrane of most cells, including
lymphocytes. It is increased with lymphocyte activation or destruction associated with HIV
disease progression, but B2-M can also be elevated with viral infections such as cytomegalovirus
and with malignant lymphomas. Neopterin, a product of macrophages, is also a measure of
immune system activation and can predict HIV disease progression. The information provided
by these tests is similar, so no advantage accrues from performing all of them
simultaneously.[209]
The best laboratory measure for determination of the progression of AIDS is the level of
HIV-1 RNA in peripheral blood. The predictive value of HIV-1 RNA levels is independent of
the CD4 lymphocyte count and of age in adults. During the acute phase of HIV infection prior to
any immune response, plasma levels of HIV-1 RNA typically exceed 10,000 copies/µL. The
initial viral load following HIV infection is 50,766 copies/mL in males and 15,103 copies/mL in
females.[200]
These levels of HIV-1 RNA generally drop, but fluctuate for a period of 6 to 9 months.
After this time, a “set point” is reached for the level of HIV-1 RNA that remains relatively
constant during the latent phase of HIV infection. Factors influencing this set point include the
strain of HIV-1, host anti-HIV response, and the number of cells, including CD4 lymphocytes
and macrophages, available for infection. The initial viremia may be higher, and the set point
may not be reached until after infancy in cases of congenital HIV infection.[210] Genital
inflammation during early HIV-1 infection is associated with higher viral load set point and CD4
depletion that predict more rapid disease progression.[211]
The set point levels of HIV-1 RNA correlate with the time to development of AIDS. The
set point can range from <50 to 1,000,000 copies/mL. Persons with a higher set point tend to
lose CD4 cells more rapidly and progress to AIDS more quickly. Levels of HIV-1 RNA can
remain at a steady state for months to years, but usually fall with time. Levels in any individual
person may vary with time and even change rapidly, though a variation of <0.7 log copies/mL
10
is typical, but an upward progression is an ominous sign of probable progression to AIDS. Less
than half of persons with low levels (<4500 copies/mL) of HIV-1 RNA have progressed to AIDS
at 10 years following seroconversion, and those with levels <200 copies/mL do not appear to
progress at all. Conversely, persons with >100,000 copies/mL are 10 times more likely to
progress to AIDS in 5 years. For persons in the top quartile (>36,270 copies/mL) the median
time to development of AIDS is 3.5 years.[86,210] The presence of opportunistic infections and
neoplasms increases the risk for progression to death from HIV infection.[212] In spite of the