The primary objective of antiretroviral therapy is to suppress viral replic
ation as soon as possible, as much as possible and for as long as possible,
a concept so clearly emphasized by David Ho in 1995: "Treat HIV early and
hard!". That, however, seems an ideal objective by a number of reasons, rec
ently recognized as fundamental: unavailability of treatments able to eradi
cate the infection, difficulty to reach compliance to HAART (Highly Active
Antiretroviral Therapy), emergence of drug resistance and cross-resistance.
(Cross)-resistance in particular has the potential both to waste future th
erapeutic options and to be transmitted during HIV infection. Therefore, HI
V pharmacoresistance has to be considered one of the most challenging focal
point in research on antiretroviral therapy. Understanding of causes, evol
utionary patterns and consequences of resistance in terms of viroimmunologi
cal and clinical response appears inescapable to strategically plan and mon
itor treatment. Rather than to eradicate the infection with regimens more a
nd more hard but more and more difficult to comply with, the realistic appr
oach is to construct a strategic therapeutic itinerary tailored to the bio-
psycho-social patient conditions and to the saving of therapeutic options.
The latter means the rational sequencing of the drug employment for a long-
term therapy, potentially life-long.