Spatial Aspects of HIV Infection - Mathematical Methods and Models in Biomedicine - page 4

acute chronic AIDS

CD4+ T cells

pVL

(weeks) time (years)

Fig. 1 Sketch of HIV disease progression. The three phases of the disease ( acute, chronic, AIDS )
characterized by the progression of the CD4 + T cell count ( dashed line ) and the plasma viral load
( solid line )areshown.The acute phase is characterized by an increase in the viral load and a rapid
loss of CD4 + T cells. After reaching a peak, the viral load declines and stabilizes on a constant
level. This chronic phase can last for months or years with a slow decline in the CD4 + T cell count.
The AIDS phase is reached if the CD4 + T cell count drops below a level of 200 cells/ μ landthe

viral load increases to a value above 125 HIV-1 RNA copies/ μ l

stages (see Fig. 1 ): The acute infection phase, which lasts on the order of weeks, is
characterized by a rapid increase in viral load and a rapid loss of CD4 + T cells from
the system. After reaching a peak, the viral load declines and stabilizes at a more or
less constant level, called the set-point viral load . Reaching this level which varies
among patients indicates the beginning of the chronic phase of the disease. The
virus can persist within a patient for the duration of months or years. The terminal
stage of the disease, the AIDS phase, is reached when the CD4 + T cell count of a
patient drops below 200 cells/

l and opportunistic infections occur. The factors that
determine the length of the chronic phase of the disease have not been determined so
far, although there exist correlations with the level of the viral load at the beginning
of the chronic phase, the set-point viral load [ 33 ], and the functionality of CD8 + T
cell immune response [ 13 ].
Therapeutic interventions available today are not able to cure the disease.
Protease inhibitors and reverse-transcriptase inhibitors interfere with the replication
of the viral pathogen. Highly active antiretroviral therapy (HAART), which relies on
a combination of these drugs, is able to effectively suppress viral replication in most
patients, so that the viral load ultimately drops to an undetectable level. However,
drug-resistant HIV mutants may exist before therapy begins or arise during therapy
and diminish its effectiveness.
Spatial effects play a role throughout the entire infection process as well as the
different stages of the disease (see Fig. 2 ).
Sexual transmission is the leading cause of HIV transmission worldwide making
the female and male genital tracts the major sites of HIV invasion [ 47 ]. To
successfully establish an infection, HIV has to cross the mucosal and epithelial
barriers at these sites. Specific locations are more exposed for viral entry than

μ