The introduction of antiretroviral therapies (ARVTs) with drugs in combination has determined a marked reduction in morbidity and mortality in national surveillance data bases. A parallel dramatic decrease in HIV plasma viral load has been observed. This evidence has been promptly transferred in therapy guidelines, in which undetectable viral load is currently considered the primary objective of ARVT. However, CD4+ T-cell counts and their trends should not be underestimated, particularly as far as their surrogate value and viro-immunological discordant trends are considered. Last but not least, long-term clinical effect of ARVT depends not only on antiviral efficacy, but also on toxicity, tolerability, patients' adherence to regimens, resistances and cross-resistances to anti-retroviral drugs before and during therapy. In conclusion, ARVT should be "tailored" both to the stage of the disease and to psycho-social profile of the patient, considering of the highest degree of importance, when possible, quality of life and preservation of future therapy options.