Biology Reference
In-Depth Information
HAART is the classical term describing the modern-day combination of anti-
retroviral agents that attack the virus at di¨erent stages of development and at
di¨erent viral structural or regulatory levels. This has dramatically reduced
morbidity and mortality from HIV and has further changed the general patho-
genesis of the HIV disease in developed countries (Oxenius et al., 2000; Sou-
deyns et al., 2000).
The e¨ects of HAART on CTL responses have been studied in some de-
tail, giving rise to two di¨erent viewpoints. Some data has suggested that the
potency of HIV-speci®c CTL declines with initiation of and complete viral
suppression by HAART. This view is explained, in part, by the need for viral
antigens to sustain the presence of strong CTL responses. The reduction of viral
burden will, therefore, lower the amount of available antigens with consequent
decline in HIV-speci®c CTL responses (Kalams et al., 1999). A second group of
data suggests that strong CTL responses are found after viral suppression with
HAART and subsequent HAART discontinuation. These data further showed
that HIV-speci®c CTL correlate with strong post-HAART suppression of vir-
aemia for up to 2 years (Ortiz et al., 1999). In a similar study at our laboratory,
we found that treatment with protease inhibitors (and not nucleoside analogs),
positively correlated with HIV-speci®c IFN-g response by CD8
cells. This and
similar studies suggest that indeed HAART improves some aspect of immune
recovery including CTL. It is not yet clear why some individuals on HAART
do have lower responses than others. Perhaps other unidenti®ed factors may be
responsible for these di¨erences in responses by di¨erent individuals.
EFFECTS OF CTL ON PLASMA VIRAL LOAD
The level of HIV viral burden has been used as one of the yardsticks for mon-
itoring the progression of an individual to AIDS. A lower viral load correlates
with better clinical status and a higher viral load represents a worsening state of
the disease. As described in previous sections, HIV-speci®c CTL has been
shown to positively correlate with some level of protection against the progres-
sion of HIV-infected individuals to AIDS. It is therefore interesting to note the
relationship between viral load and CTL responses in HIV-infected individuals.
Information currently available indicates that there is a strong correlation
between viral load and CTL responses in di¨erent groups of individuals
(Ariyoshi et al., 1995; Klenerman et al., 1996). Some have found both negative
and positive correlations between viral load lowered by drugs (see above) and
CTL responses (Borrow et al., 1994; Koup et al., 1994). Most still conclude
that there is an inverse correlation. In another study carried out in our labora-
tory, 17 HIV-infected long-term survivors, who have remained healthy for 10
years despite varying levels of both CD4
T cells and viral burden, were fol-
lowed up for 10±14 years (Betts et al., 1999). Changes in both their viral load
and CTL activities were measured and compared over time. Figure 6.4 shows
the inverse correlation that existed between Pol-speci®c CTL and the viral load.
