Biology Reference
In-Depth Information
structured'' treatment interruptions very often occur in the real world because
of drug toxicity, intercurrent illness, boredom with treatment, chaotic life style,
and uncertainty over therapeutic e¨ects. Many patients still wish to stop ther-
apy temporarily (or permanently), and it is the unplanned treatment interrup-
tion (UTI) that currently dominates the ®eld. Therefore, STI strategies may go
quite beyond the issue of re-stimulating immune response for persons maxi-
mally suppressed, or to drive back wild virus in persons with multiple failures
and multidrug-resistant virus: to ``give patient's a break,'' with the ultimate
goal of prolonging the bene®cial e¨ects of antiretroviral treatment over the long
term (and, on another note, the concept of STI may also have a unprecedented
impact, if proven, in resource-poor settings).
However, many questions still need to be answered in controlled clinical
trials before this strategy can be adopted: what are the long-term e¨ects on viral
load and CD4 cell count? Will the response to therapy reinstitution be repro-
ducible over long time periods? What occurs in terms of genotypic/phenotypic
resistance over time? Is STI strategy comparable, superior, or inferior to thera-
peutic vaccination? Will the response to STI be the same for persons having
received PI or non-PI-containing regimens? What happens during STI in the
di¨erent HIV compartments and reservoirs?
In conclusion, structured treatment interruptions, intermittent treatment, or
pulsed therapy has distinct attractions for patients and healthcare providers,
with potential for reduced toxicity, improved tolerance, greater adherence to
dosing schedules, and lower cost. These ®rst studies of interrupting HIV treat-
ment seem to challenge the assumption that only harm would occur and to
support the evidence that the virus is more forgiving than has been realized.
Immune Intervention
A remarkable amount of data has been recently produced, showing that a spe-
ci®c immune response is evoked by HIV during primary infection. This consists
in the appearance of p24 Gag-speci®c T-helper responses and cytotoxic T lym-
phocytes (CTL) speci®c for viral antigens. The strength of the CTL response
seems to be a key factor in determining the viral set-point, which in turn will
predict the future outcome in the individual patient. This reactivity usually de-
clines within the ®rst months or years of infection, unless a potent antiretroviral
treatment is initiated during the acute phase. Indeed, in this case, strong and
persistent gag-speci®c T helper CD4 and CTL activity is maintained in a high
proportion of subjects, whereas among patients having initiated highly active
antiretroviral therapy (HAART ) during the chronic phase the same propor-
tion is around 5%, or even less in those with CD4
cell count below 250/mm
3
.
Unfortunately, early treatment, though able to keep plasma viral load to un-
detectable levels and to maintain a vigorous anti-HIV immune response, seems
unable to prevent the establishment of a latent reservoir of HIV, represented by
resting CD4
T cells.
