Immune control of HIV-1 infection after therapy interruption: immediate versus deferred antiretroviral therapy.
BACKGROUND
The optimal stage for initiating antiretroviral therapies in HIV-1 bearing patients is still a matter of debate.


METHODS
We present computer simulations of HIV-1 infection aimed at identifying the pro et contra of immediate as compared to deferred Highly Active Antiretroviral Therapy (HAART).


RESULTS
Our simulations highlight that a prompt specific CD8+ cytotoxic T lymphocytes response is detected when therapy is delayed. Compared to very early initiation of HAART, in deferred treated patients CD8+ T cells manage to mediate the decline of viremia in a shorter time and, at interruption of therapy, the virus experiences a stronger immune pressure. We also observe, however, that the immunological effects of the therapy fade with time in both therapeutic regimens. Thus, within one year from discontinuation, viral burden recovers to the value at which it would level off in the absence of therapy.In summary, simulations show that immediate therapy does not prolong the disease-free period and does not confer a survival benefit when compared to treatment started during the chronic infection phase.


CONCLUSIONS
Our conclusion is that, since there is no therapy to date that guarantees life-long protection, deferral of therapy should be preferred in order to minimize the risk of adverse effects, the occurrence of drug resistances and the costs of treatment.
Paci
Paola
P
Institute for Computing Applications Mauro Picone, National Research Council, Rome, Italy. p.paci@iac.cnr.it
Carello
Rossella
R
Bernaschi
Massimo
M
D'Offizi
Gianpiero
G
Castiglione
Filippo
F
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015331:Cohort Studies; D003198:Computer Simulation; D003602:Cytotoxicity, Immunologic; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D010865:Pilot Projects; D012367:RNA, Viral / Q000097:blood; D013997:Time Factors; D014766:Viremia; D055815:Young Adult
D019380:Anti-HIV Agents; D012367:RNA, Viral