Page 35 - AIDSBK23C

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mediated immune responses play a role. The CD4 lymphocytes rebound in number after primary
HIV infection, but not to pre-infection levels. Seroconversion with detectable HIV antibody by
laboratory testing such as enzyme immunoassay accompanies this immune response, sometimes
in as little as a week, but more often in two to four weeks.[21,22,54] Prolonged HIV-1 infection
without evidence for seroconversion, however, is an extremely rare event.[196] Persons infected
with HIV who develop an acute retroviral illness and who have a shorter time to seroconversion
tend to progress to AIDS faster than persons with longer seroconversion times.[197]
The HIV infection then becomes clinically "latent." During this phase, there is little or
no viral replication detectable in peripheral blood mononuclear cells and little or no culturable
virus in peripheral blood. The CD4 lymphocyte count remains moderately decreased. However,
the immune response to HIV is insufficient to prevent continued viral replication within
lymphoid tissues. Though lymph nodes may not become enlarged and their architecture is
maintained, active viral replication continues.[41,198] Tests for HIV antibody will remain
positive during this time but p24 antigen tests are usually negative. Seroreversion, or loss of
antibody, is a rare event in HIV-infected persons, even those on antiretroviral therapy with
prolonged suppression of viremia, and has been so far only reported in patients receiving
antiretroviral therapy early after infection.[199]
Though the time to development of AIDS is statistically similar in men and women, the
viral load of women tends to be lower. Women with half the viral load of men have a similar
time to development of AIDS as men. Women with the same viral load as men have a 1.6-fold
higher risk of AIDS. The biologic basis for this difference is unclear.[200]
In many viral infections, an immune response consisting of virus-specific CD4
lymphocytes helps to contain the infection. However, such a response is typically lacking in
HIV-infected persons. A minority of HIV infected persons does mount a persistent polyclonal
CD4 lymphocyte proliferation directed against HIV, which controls viremia. This response
results in a cytokine response with elaboration of interferon gamma and beta chemokines. Such
a response may also occur with antiretroviral therapy.[201]
As FDC’s are diminished over time with HIV infection, the capacity for stimulation of
CD4 lymphocytes is also diminished, and CD4 memory cells decline as well. However,
remaining FDCs continue to promote ongoing production of antibody to HIV. CD4 memory
cells may also be lost by formation of syncytia with infected FDCs. Finally, when the stage of
AIDS is reached, development of FDCs from stem cells is diminished.[92]
Cells of the innate immune system, including mononuclear phagocytic cells (monocytes
and macrophages) are infected by HIV, and these relatively long-lived cells become a reservoir
for infection. However, HIV can disrupt innate immune processes.[202] Also, HIV viremia is
associated with increased Toll-like receptor (TLR) expression and responsiveness that plays a
roll in innate immune dysfunction.[203] Such disruption makes bacterial infections more likely
to occur.
Though no clinical signs and symptoms are apparent, the immune system, primarily
through depletion of CD4 lymphocytes, deteriorates. Not only CD4 cells are lost, but also
cytotoxic CD8 cells, and the most avid ones in particular, leading to exhaustion of controlling T
cell responses. Levels of cytokines driving lymphoid proliferation, such as IL-2, decrease.[87]
The virus continues to replicate in lymphoid organs, despite a low level or lack of viremia.[54]
HIV can be found trapped extracellularly in the follicular dendritic cell network of germinal
centers in lymphoid tissues or intracellularly as either latent or replicating virus in mononuclear
cells. The period of clinical latency with HIV infection, when infected persons appear in good