Biology Reference
In-Depth Information
lain et al., 2001). These observations led to the concept of structured therapeu-
tic interruptions (STI ), which might re-increase HIV-speci®c immunity by
transiently but recurrently re-exposing the patient to HIV virus particles during
treatment windows. This strategy might have some bene®t when applied after
treatment of primary infection (Lisziewicz et al., 1999; Ortiz et al., 1999;
Rosenberg et al., 2000). We reported, however, that re-expansions of HIV-
speci®c CD4 T cells were usually only transient in chronically infected patients
(Carcelain et al., 2001).
Another safer strategy is currently proposed to restore HIV-speci®c immu-
nity and to limit drug toxicity in treated patients by re-immunizing patients
against HIV with candidate vaccines (Autran and Carcelain, 2000). Inactivated
HIV particles and recombinant viral vectors, such as canary pox (Goh et al.,
2000) or DNA immunizations (Calarota et al., 1999), are currently being tested
for their ability to restore CD4 T-cell responses to HIV proteins in treated
patients (Valentine). Encouraging preliminary results also suggest that cytokine
therapy such as IL-2 might help accelerate immune reconstitution (Chun et al.,
1999; Cooper and Emery, 1999; Hengge et al., 1998; Imama et al., 1999;
Katlama et al., 2000; Kovacs et al., 1996). Immune-based strategies aimed at
restoring immunity against HIV might also incorporate other adjuvant cyto-
kines (Landay et al., 1996; McFarland et al., 1998) that enhance the functions
of antigen-presenting cells and their capacity to generate strong and protective
CD4 Th1 and CD8 cell responses against HIV.
CONCLUSION
In conclusion, new regimens of antiretroviral therapy have successfully restored
a normal or subnormal CD4 compartment and protection against opportunistic
pathogens. The major condition required for immune reconstitution is an e½-
cient and durable inhibition of virus replication. These successes demonstrate
that HIV does not de®nitively alter the lymphoid tissues or the immune de-
fenses, even after years of infection and severe immune suppression. Despite the
many controversies about the ®ne mechanisms of such recovery (Miedema,
2000) or about whether the immune system can perfectly recover, many factors
are at work (McCune). Three mechanisms certainly allow CD4 recovery: 1)
redistribution of memory CD4 T cells from tissues where they had been pre-
viously sequestered; 2) regeneration of naive T cells from thymic origin; and 3)
reduction of the in¯ammatory syndrome. Initiating HAART in late or in early
disease might di¨er, however, by the time required to reach normalized immune
functions and cell counts and by the lack of ampli®cation of HIV-speci®c CD4
T cells in late disease. It is obvious that only long-lasting control of HIV allows
immune restoration (Saag, 1999). Lack of reconstitution of a solid immunity
against HIV itself is currently increasing the need for additive therapeutic
strategies based upon immune interventions.
